Behavioural profiles of two Wistar rat lines selectively bred for high or low anxiety-related behaviour.

PubMed

Liebsch, G; Montkowski, A; Holsboer, F; Landgraf, R

1998-08-01

Over the past years, two breeding lines, derived originally from outbred Wistar rats, have been established that differ markedly and consistently in their anxiety-related behaviour in the elevated plus-maze. At the age of ten weeks, rats were tested once on the elevated plus-maze and the males and females displaying the most anxious and the least anxious behaviour were sib-mated to start a new generation of the high anxiety-related behaviour (HAB) and the low anxiety-related behaviour (LAB) lines, respectively. The resulting difference in emotionality between these two lines was also evident in an open field test and correlated with differences in the forced swim test. In the open field, the HAB rats tended to be less active and explored the central zone of the open field much less than the LAB animals. In the forced swim test, HAB rats started floating earlier, spent significantly more time in this immobile posture and struggled less than LAB rats. However, in an olfactory-cued social discrimination task there was no difference between male and female animals from either line. The overall performance in these various behavioural tests suggests that selective breeding has resulted in rat lines not only differing markedly in their innate anxiety-related behaviour in the plus-maze, but also in other stress-related behavioural performances, suggesting a close link between the emotional evaluation of a novel and stressful situation and an individual's coping strategy.

Role of thirst and visual barriers in the differential behavior displayed by streptozotocin-treated rats in the elevated plus-maze and the open field test.

PubMed

Rebolledo-Solleiro, Daniela; Crespo-Ramírez, Minerva; Roldán-Roldán, Gabriel; Hiriart, Marcia; Pérez de la Mora, Miguel

2013-08-15

Conflicting results have been obtained by several groups when studying the effects of streptozotocin (STZ)-treated rats in the elevated plus-maze (EPM). Since thirst is a prominent feature in STZ-induced diabetic-like condition, we studied whether the walls of the closed arms of the EPM, by limiting the search for water in the environment, may contribute to the observed differential behavioral outcomes. The aim of this study was to ascertain whether visual barriers within the EPM have an influence on the behavior of STZ-treated rats in this test of anxiety. A striking similarity between STZ-treated (50 mg/kg, i.p., in two consecutive days) and water deprived rats (72 h) was found in exploratory behavior in the EPM, showing an anxiolytic-like profile. However the anxiolytic response of STZ-treated rats exposed to the EPM shifts into an anxiogenic profile when they are subsequently tested in the open-field test, which unlike the EPM is devoid of visual barriers. Likewise, water deprived rats (72 h) also showed an anxiogenic profile when they were exposed to the open-field test. Our results indicate that experimental outcomes based on EPM observations can be misleading when studying physiological or pathological conditions, e.g. diabetes, in which thirst may increase exploratory behavior. © 2013.

Rearing in enriched environment increases parvalbumin-positive small neurons in the amygdala and decreases anxiety-like behavior of male rats.

PubMed

Urakawa, Susumu; Takamoto, Kouich; Hori, Etsuro; Sakai, Natsuko; Ono, Taketoshi; Nishijo, Hisao

2013-01-25

Early life experiences including physical exercise, sensory stimulation, and social interaction can modulate development of the inhibitory neuronal network and modify various behaviors. In particular, alteration of parvalbumin-expressing neurons, a gamma-aminobutyric acid (GABA)ergic neuronal subpopulation, has been suggested to be associated with psychiatric disorders. Here we investigated whether rearing in enriched environment could modify the expression of parvalbumin-positive neurons in the basolateral amygdala and anxiety-like behavior. Three-week-old male rats were divided into two groups: those reared in an enriched environment (EE rats) and those reared in standard cages (SE rats). After 5 weeks of rearing, the EE rats showed decreased anxiety-like behavior in an open field than the SE rats. Under another anxiogenic situation, in a beam walking test, the EE rats more quickly traversed an elevated narrow beam. Anxiety-like behavior in the open field was significantly and negatively correlated with walking time in the beam-walking test. Immunohistochemical tests revealed that the number of parvalbumin-positive neurons significantly increased in the basolateral amygdala of the EE rats than that of the SE rats, while the number of calbindin-D28k-positive neurons did not change. These parvalbumin-positive neurons had small, rounded soma and co-expressed the glutamate decarboxylase (GAD67). Furthermore, the number of parvalbumin-positive small cells in the basolateral amygdala tended to positively correlate with emergence in the center arena of the open field and negatively correlated with walking time in the beam walking test. Rearing in the enriched environment augmented the number of parvalbumin-containing specific inhibitory neuron in the basolateral amygdala, but not that of calbindin-containing neuronal phenotype. Furthermore, the number of parvalbumin-positive small neurons in the basolateral amygdala was negatively correlated with walking time in the beam walking test and tended to be positively correlated with activity in the center arena in the open field test. The results suggest that rearing in the enriched environment augmented parvalbumin-positive specific neurons in the basolateral amygdala, which induced behavioral plasticity that was reflected by a decrease in anxiety-like behavior in anxiogenic situations.

Rearing in enriched environment increases parvalbumin-positive small neurons in the amygdala and decreases anxiety-like behavior of male rats

PubMed Central

2013-01-01

Background Early life experiences including physical exercise, sensory stimulation, and social interaction can modulate development of the inhibitory neuronal network and modify various behaviors. In particular, alteration of parvalbumin-expressing neurons, a gamma-aminobutyric acid (GABA)ergic neuronal subpopulation, has been suggested to be associated with psychiatric disorders. Here we investigated whether rearing in enriched environment could modify the expression of parvalbumin-positive neurons in the basolateral amygdala and anxiety-like behavior. Results Three-week-old male rats were divided into two groups: those reared in an enriched environment (EE rats) and those reared in standard cages (SE rats). After 5 weeks of rearing, the EE rats showed decreased anxiety-like behavior in an open field than the SE rats. Under another anxiogenic situation, in a beam walking test, the EE rats more quickly traversed an elevated narrow beam. Anxiety-like behavior in the open field was significantly and negatively correlated with walking time in the beam-walking test. Immunohistochemical tests revealed that the number of parvalbumin-positive neurons significantly increased in the basolateral amygdala of the EE rats than that of the SE rats, while the number of calbindin-D28k-positive neurons did not change. These parvalbumin-positive neurons had small, rounded soma and co-expressed the glutamate decarboxylase (GAD67). Furthermore, the number of parvalbumin-positive small cells in the basolateral amygdala tended to positively correlate with emergence in the center arena of the open field and negatively correlated with walking time in the beam walking test. Conclusion Rearing in the enriched environment augmented the number of parvalbumin-containing specific inhibitory neuron in the basolateral amygdala, but not that of calbindin-containing neuronal phenotype. Furthermore, the number of parvalbumin-positive small neurons in the basolateral amygdala was negatively correlated with walking time in the beam walking test and tended to be positively correlated with activity in the center arena in the open field test. The results suggest that rearing in the enriched environment augmented parvalbumin-positive specific neurons in the basolateral amygdala, which induced behavioral plasticity that was reflected by a decrease in anxiety-like behavior in anxiogenic situations. PMID:23347699

Increased sensitivity to the acute effects of MDMA ("ecstasy") in female rats.

PubMed

Palenicek, T; Votava, M; Bubenikova, V; Horacek, J

2005-11-15

Behavioral effects of +/-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are relatively well described in humans as well as in animals. However, little is known about gender differences to the effects of MDMA. The aim of our study was to evaluate gender differences in stimulant effects of MDMA (2.5, 5.0, and 10.0 mg/kg subcutaneously (s.c.)) in male and female Wistar rats. We have used three behavioral methods (activity cage, open field, and elevated plus-maze) each describing a different pattern of spontaneous behavior. In the activity cage, 30 min after the MDMA administration, horizontal and vertical locomotor activities were registered for a period of 3 min. In the open field test rats were placed into an arena 15 min after drug treatment and locomotor activity was registered for a period of 30 min. Finally, in the elevated plus-maze test, rats were given MDMA 30 min prior to measurements and subsequently they were tested in the maze for a period of 5 min. In our experiments we observed a dose-dependent locomotion-enhancing effect of MDMA both in male and female rats in both locomotor tests. Female rats were more sensitive to the locomotor-stimulating effect than males in both tests, suggesting higher sensitivity to the stimulatory effect of MDMA. Further on, MDMA increased thigmotaxis in female rats in the open field test and decreased "anxious-like" behavior in the elevated plus-maze in both genders. In conclusion, we observed higher sensitivity of females to the locomotor-stimulant effect of MDMA. Increased sensitivity of females to the behavioral effects of MDMA can be explained by increased reactivity of serotonergic and dopaminergic systems.

Resident intruder paradigm-induced aggression relieves depressive-like behaviors in male rats subjected to chronic mild stress

PubMed Central

Wei, Sheng; Ji, Xiao-wei; Wu, Chun-ling; Li, Zi-fa; Sun, Peng; Wang, Jie-qiong; Zhao, Qi-tao; Gao, Jie; Guo, Ying-hui; Sun, Shi-guang; Qiao, Ming-qi

2014-01-01

Background Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that the resident intruder paradigm (RIP) results in aggressive behavior in male rats. However, it is not known how resident intruder paradigm-induced aggression affects depressive-like behavior in isolated male rats subjected to chronic mild stress (CMS), which is an animal model of depression. Material/Methods Male Wistar rats were divided into 3 groups: non-stressed controls, isolated rats subjected to the CMS protocol, and resident intruder paradigm-exposed rats subjected to the CMS protocol. Results In the sucrose intake test, ingestion of a 1% sucrose solution by rats in the CMS group was significantly lower than in control and CMS+RIP rats after 3 weeks of stress. In the open-field test, CMS rats had significantly lower open-field scores compared to control rats. Furthermore, the total scores given the CMS group were significantly lower than in the CMS+RIP rats. In the forced swimming test (FST), the immobility times of CMS rats were significantly longer than those of the control or CMS+RIP rats. However, no differences were observed between controls and CMS+RIP rats. Conclusions Our data show that aggressive behavior evoked by the resident intruder paradigm could relieve broad-spectrum depressive-like behaviors in isolated adult male rats subjected to CMS. PMID:24911067

Acute food deprivation separates motor-activating from anxiolytic effects of caffeine in a rat open field test model.

PubMed

Schulz, Daniela

2018-03-14

Similar doses of caffeine have been shown to produce either anxiolytic or anxiogenic effects in rats. The reasons for these conflicting results are not known. We hypothesized that food deprivation stress interacts with the stimulant effects of caffeine to increase anxiety-like behavior. We tested 32 female Sprague Dawley rats in a dim open field for 10 min. Half of the animals were food deprived for 24 h and injected (intraperitoneal) with caffeine (30 mg/kg; n=7) or deionized water (n=8) 20 min before the open field test. The other half was nondeprived and injected with caffeine (30 mg/kg; n=8) or deionized water (n=9). Results showed that nondeprived rats injected with caffeine moved longer distances and at a greater speed in the periphery and moved longer distances and spent more time in the center than rats treated with vehicle, indicative of motor-activating and/or anxiolytic effects of caffeine. Rats that were food deprived and injected with caffeine moved longer distances in the center and tended to spend more time there, indicative of anxiolysis. We conclude that caffeine had two effects on behavior, motor activation and a reduction of anxiety, and that food deprivation separated these effects.

Intranasal administration of testosterone increased immobile-sniffing, exploratory behavior, motor behavior and grooming behavior in rats.

PubMed

Zhang, Guoliang; Shi, Geming; Tan, Huibing; Kang, Yunxiao; Cui, Huixian

2011-04-01

Currently, testosterone (T) replacement therapy is typically provided by oral medication, injectable T esters, surgically implanted T pellets, transdermal patches and gels. However, most of these methods of administration are still not ideal for targeting the central nervous system. Recently, therapeutic intranasal T administration (InT) has been considered as another option for delivering T to the brain. In the present study, the effects of 21-day InT treatment were assessed on open field behavior in gonadectomized (GDX) rats and intact rats. Subcutaneous injections of T at same dose were also tested in GDX rats. A total of 12 behavioral events were examined in GDX groups with or without T and in intact groups with or without InT. Significant decreases in open field activity were observed in rats after GDX without InT compared to sham-operated rats. The open field activity scores for most tests significantly increased with InT treatment in GDX rats and in intact rats compared with the corresponding GDX rats and intact rats. Intranasal administration of T improved the reduced behaviors resulted from T deficiency better than subcutaneous injection of T, demonstrating that T can be delivered to the brain by intranasal administration. Our results suggest that intranasal T delivery is an effective option for targeting the central nervous system. Copyright © 2011 Elsevier Inc. All rights reserved.

Science Operations Development for Field Analogs: Lessons Learned from the 2010 Desert RATS Test

NASA Technical Reports Server (NTRS)

Eppler, D. B.; Ming, D. W.

2011-01-01

Desert Research and Technology Studies (Desert RATS) is a multi-year series of hardware and operations tests carried out annually in the high desert of Arizona on the San Francisco Volcanic Field. Conducted since 1997, these activities are designed to exercise planetary surface hardware and operations in conditions where long-distance, multi-day roving is achievable. Such activities not only test vehicle subsystems through extended rough-terrain driving, they also stress communications and operations systems and allow testing of science operations approaches to advance human and robotic surface capabilities.

D-RATS 2011: RAFT Protocol Overview

NASA Technical Reports Server (NTRS)

Utz, Hans

2011-01-01

A brief overview presentation on the protocol used during the D-RATS2011 field test for file transfer from the field-test robots at Black Point Lava Flow AZ to Johnson Space Center, Houston TX over a simulated time-delay. The file transfer actually uses a commercial implementation of an open communications standard. The focus of the work lies on how to make the state of the distributed system observable.

NASA's Habitat Demonstration Unit (HDU) Pressurized Excursion Module (PEM) In-Field Demonstration at Desert RATS 2010

NASA Technical Reports Server (NTRS)

Tri, Terry O.; Kennedy, Kriss J.; Toups, Larry; Gill, Tracy R.; Howe, A. Scott

2011-01-01

This paper describes the construction, assembly, subsystem integration, transportation, and field testing operations associated with the Habitat Demonstration Unit (HDU) Pressurized Excursion Module (PEM) and discusses lessons learned. In a one-year period beginning summer 2009, a tightly scheduled design-develop-build process was utilized by a small NASA "tiger team" to produce the functional HDU-PEM prototype in time to participate in the 2010 Desert Research and Technology Studies (Desert RATS) field campaign. The process required the coordination of multiple teams, subcontractors, facility management and safety staff. It also required a well-choreographed material handling and transportation process to deliver the finished product from the NASA-Johnson Space Center facilities to the remote Arizona desert locations of the field test. Significant findings of this paper include the team s greater understanding of the HDU-PEM s many integration issues and the in-field training the team acquired which will enable the implementation of the next-generation of improvements and development of high-fidelity field operations in a harsh environment. The Desert RATS analog environment is being promoted by NASA as an efficient means to design, build, and integrate multiple technologies in a mission architecture context, with the eventual goal of evolving the technologies into robust flight hardware systems. The HDU-PEM in-field demonstration at Desert RATS 2010 provided a validation process for the integration team, which has already begun to retool for the 2011 field tests that require an adapted architecture.

[OPEN FIELD BEHAVIOR AS A PREDICTIVE CRITERIA REFLECTING RATS CORTICOSTERONELEVEL BEFORE AND AFTER STRESS].

PubMed

Umriukhin, P E; Grigorchuk, O S

2015-12-01

In the presented study we investigated the possibility to use the open field behavior data for prediction of corticosterone level in rat blood plasma before and after stress. It is shown that the most reliable open field behavior parameters, reflecting high probability of significant upregulation of corticosterone after 3 hours of immobilization, are the short latency of first movement and low locomotor activity during the test. Rats with high corticosterone at normal non-stress conditions are characterized by low locomotor activity and on the contrary long latency period for the entrance of open field center.

Tools and technologies needed for conducting planetary field geology while on EVA: Insights from the 2010 Desert RATS geologist crewmembers

NASA Astrophysics Data System (ADS)

Young, Kelsey; Hurtado, José M.; Bleacher, Jacob E.; Brent Garry, W.; Bleisath, Scott; Buffington, Jesse; Rice, James W.

2013-10-01

The tools used by crews while on extravehicular activity during future missions to other bodies in the Solar System will be a combination of traditional geologic field tools (e.g. hammers, rakes, sample bags) and state-of-the-art technologies (e.g. high definition cameras, digital situational awareness devices, and new geologic tools). In the 2010 Desert Research and Technology Studies (RATS) field test, four crews, each consisting of an astronaut/engineer and field geologist, tested and evaluated various technologies during two weeks of simulated spacewalks in the San Francisco volcanic field, Arizona. These tools consisted of both Apollo-style field geology tools and modern technological equipment not used during the six Apollo lunar landings. The underlying exploration driver for this field test was to establish the protocols and technology needed for an eventual manned mission to an asteroid, the Moon, or Mars. The authors of this paper represent Desert RATS geologist crewmembers as well as two engineers who worked on technology development. Here we present an evaluation and assessment of these tools and technologies based on our first-hand experience of using them during the analog field test. We intend this to serve as a basis for continued development of technologies and protocols used for conducting planetary field geology as the Solar System exploration community moves forward into the next generation of planetary surface exploration.

Desert Research and Technology Studies (RATS) 2007 Field Campaign Objectives and Results

NASA Technical Reports Server (NTRS)

Kosmo, Joseph; Romig, Barbara

2008-01-01

Desert "RATS" (Research and Technology Studies) is a combined, multi-discipline group of inter-NASA center scientists and engineers, net-working and collaborating with representatives of industry and academia, for the purpose of conducting planetary surface exploration-focused remote field exercises. These integrated testing exercises conducted under representative analog Lunar and Mars surface terrain conditions, provide NASA the capability to validate experimental prototype hardware and software systems as well as to evaluate and develop mission operational techniques in order to identify and establish technical requirements and identify potential technology "gaps" applicable for future planetary human exploration. The 2007 D-RATS field campaign test activities were initiated based on the major themes and objectives of a notional 5-year plan developed for conducting relative analog test activities in support of the engineering evaluation and assessment of various system architectural requirements, conceptual prototype support equipment and selected technologies necessary for the establishment of a lunar outpost. Specifically, the major objectives included measuring task efficiency during robot, human, and human-robot interactive tasks associated with lunar outpost site surveying and reconnaissance activities and deployment of a representative solar panel power and distribution system. In addition, technology demonstrations were conducted with a new Lithium-ion battery and autonomous software to coordinate multiple robot activities. Secondary objectives were evaluating airlock concept mockups and prototype removable space suit over-garment elements for dust mitigation, and upgrades to the prototype extravehicular activities (EVA) communication and information system. Dry run test activities, prior to testing at a designated remote field site location, were initially conducted at the Johnson Space Center (JSC) Remote Field Demonstration Test Site. This is a multi-acre external test site located at JSC and has detailed representative terrain features simulating both Lunar and Mars surface characteristics. Both the local JSC and remote field test sites have terrain conditions that are representative and characteristic of both the Moon and Mars, such as strewn rock and volcanic ash fields, craters, rolling plains, hills, gullies, slopes, and outcrops. The D-RATS 2007 field campaign, representing the completion of its tenth year of analog testing, was conducted at the large Cinder Lake volcanic ash bed area adjacent to Flagstaff, Arizona.

Effects of 4-hydroxyisoleucine from Fenugreek Seeds on Depression-like Behavior in Socially Isolated Olfactory Bulbectomized Rats.

PubMed

Kalshetti, Padmaja B; Alluri, Ramesh; Mohan, Vishwaraman; Thakurdesai, Prasad Arvind

2015-10-01

Antidepressant-like effects of (2S, 3R, 4S)-4-hydroxyisoleucine (4-HI), a major amino acid from fenugreek seeds, has been reported in the animal model of acute depression. To evaluate effects of subacute administration of 4-HI in animal model of stress-induced depression namely socially isolated olfactory bulbectomized rats. Bilateral olfactory bulbectomy (OBX) were induced in 30 Sprague-Dawley rats. After recovery period of 14 days, rats were randomized into five groups of 6 rats each and stressed with social isolation (individual housing). The rats were orally treated with either vehicle (OBX-Iso), positive control, fluoxetine (30 mg/kg) or 4-HI (10, 30, 100 mg/kg) once a day from day 14 onward. Separate group of rats with social isolation but without OBX (Sham-Iso) was also maintained. The behavioral depression and anxiety related parameters using open field test (OFT), sucrose intake test, novelty suppressed feeding (NSF) and forced swim test (FST), and neurochemical estimation (brain monoamines viz., serotonin and nor-adrenaline, serotonin turnover, and serum cortisol) were performed. Data was analyzed by either two-way ANOVA (OFT and FST) or one-way ANOVA (sucrose intake test, NSF, and neurochemical estimation) followed by Dunnett's multiple comparisons test. Differences were considered significant at P < 0.05. The significant and dose-dependent protection from behavioral and neurochemical changes were observed in 4-HI co-administrated OBX-Iso rats. 4-HI demonstrated the antidepressant and antianxiety effects in socially isolated stress-induced OBX rats with possible involvement of multiple stress relieving mechanisms. In this study, the subacute pretreatment of 4-HI showed strong and dose-dependent prevention of isolation stress related behavioral and neurochemical responses in olfactory bulbectomized rats. The prevention of hyperactive HPA axis in OBX-Iso stress-induced rats can be envisaged as probable mechanism of antidepressant and antianxiety effects of 4-HI. Effect of 4-hydroxyisoleucine (4-HI) in olfactory bulbectomized and socially isolated (Iso) rats was evaluated4-HI showed significant and dose-dependent antidepressant effects during novelty suppressed feeding (NSF) and forced swim test (FST)4-HI showed significant and dose-dependent antianxiety effects during OFT (open field test) and sucrose intake test4-HI showed protection from OBX-Iso stress-induced brain monoamines, serotonin turnover, and serum cortisol level elevation. Abbreviations used: SSRI: Selective Serotonin Reuptake Inhibitor; 4-HI: (2S, 3R, 4S)-4-hydroxyisoleucine; OBX: Olfactory bulbectomy; CPCSEA: Committee for the Purpose of Control and Supervision of Experiments on Animals; OFT: Open Field Test; NSF: Novelty Suppressed Feeding; FST: Forced Swimming Test; 5HT: 5-Hydroxytryptamine; 5-HIAA: 5-Hydroxyindoleacetic Acid; NA: Nor-adrenaline; and HPA: Hypothalamic-Pituitary Adrenal.

Anxiogenic effects of chronic exposure to nandrolone decanoate (ND) at supraphysiological dose in rats: a brief report.

PubMed

Rosic, Gvozden; Joksimovic, Jovana; Selakovic, Dragica; Milovanovic, Dragan; Jakovljevic, Vladimir

2014-01-01

Nandrolone decanoate (ND) is frequently used anabolic androgenic steroid (AAS) among the athletes. Despite the health risks, there is significant increase in prevalence of AAS abuse. The aim of this study was to investigate the effects of chronic exposure to ND at supraphysiological dose (to mimic the doses for human AAS abusers) on anxiety levels in adult rats. We performed several behavioral tests (open field test, elevated plus maze test, beam-walking test, evoked beam-walking test and tail suspension test) for estimation of anxiety in rats. Adult rats received 20 mg/kg intraperitoneal injection of ND weekly for four weeks. Behavioral test were performed on the seventh day after the last dose of ND. Anxiogenic-like pattern of behavior was clearly observed in several behavioral tests, such as open field test (decrease of total distance moved and cumulative duration of moving, decrease of an average velocity of the animals, decrease of frequency and total time in centre zone); elevated plus maze (decreased total time spent in open arms and the number of entries in open arms of the elevated plus maze); evoked beam-walking test (decreased time to cross the beam) and tail suspension test (increased latency to first immobility and decreased total duration of immobility). Results of this study show that four-week treatment with the supraphysiological dose of ND produced anxiogenic effects in sedentary male rats. Our results show that rats after chronic treatment with a supraphysiological dose of ND exhibited anxiety-like behavior.

The effects of central administration of physostigmine in two models of anxiety.

PubMed

Sienkiewicz-Jarosz, H; Maciejak, Piotr; Krzaścik, Paweł; Członkowska, Agnieszka I; Szyndler, Janusz; Bidziński, Andrzej; Kostowski, Wojciech; Płaźnik, Adam

2003-05-01

The effects of intracerebroventricular and intraseptal (the medial septum) administration of a prototypical acetylcholinesterase inhibitor (AChE-I), physostigmine, and a classic benzodiazepine midazolam on rat behavior in the open field test of neophobia and in the conditioned fear test (freezing reaction) were examined in rats. In the open field test of neophobia midazolam and physostigmine increased at a limited dose range, rat exploratory activity, after intracerebroventricular injection. Physostigmine produced in addition the hyperlocomotory effect. Following intraseptal injections, only physostigmine selectively prolonged the time spent by animals in the central sector of the open field. In the model of a conditioned fear, both midazolam and physostigmine inhibited rat freezing reaction to the aversively conditioned context after intracerebroventricular, but not after intraseptal, pretrial drug administration. The presented data support the notion about the selective anxiolytic-like effects of some AChE-Is. It appears, therefore, that the calming and sedative effects of AChE-Is observed in patients with Alzheimer's disease may be directly related to their anxiolytic action, independent of an improvement in cognitive functions, which in turn may decrease disorientation-induced distress and anxiety.

Comparison of Three Wind Measuring Systems for Flight Test

NASA Technical Reports Server (NTRS)

Teets, Edward H., Jr.; Harvey, Philip O.

2000-01-01

A preliminary field test of the accuracy of wind velocity measurements obtained using global positioning system-tracked rawinsonde balloons has been performed. Wind comparisons have been conducted using global positioning system (GPS) and radio automatic theodolite sounder (RATS) rawinsondes and a high-precision range instrumentation radar-tracked reflector. Wind velocity differences between the GPS rawinsondes and the radar were significantly less than between the RATS rawinsondes and the radar. These limited test results indicate a root-mean-square wind velocity difference from 4.98 kn (2.56 m/sec) for the radar and RATS to 1.09 kn (0.56 m/sec) for the radar and GPS. Differences are influenced by user reporting requirements, data processing techniques, and the inherent tracking accuracies of the system. This brief field test indicates that the GPS sounding system tracking data are more precise than the RATS system. When high-resolution wind data are needed, use of GPS rawinsonde systems can reduce the burden on range radar operations.

Effects of social defeat on sleep and behaviour: importance of the confrontational behaviour.

PubMed

Kinn Rød, Anne Marie; Murison, Robert; Mrdalj, Jelena; Milde, Anne Marita; Jellestad, Finn Konow; Øvernes, Leif Arvid; Grønli, Janne

2014-03-29

We studied the short- and long-term effects of a double social defeat (SD) on sleep parameters, EEG power, behaviour in the open field emergence test, corticosterone responsiveness, and acoustic startle responses. Pre-stress levels of corticosterone were assessed before all rats were surgically implanted with telemetric transmitters for sleep recording, and allowed 3weeks of recovery. Rats in the SD group (n=10) were exposed to 1hour SD on two consecutive days, while control rats (n=10) were left undisturbed. Telemetric sleep recordings were performed before SD (day -1), day 1 post SD, and once weekly for 3weeks thereafter. The open field emergence test was performed on day 9 and weekly for 2weeks thereafter. Blood samples for measures of corticosterone responsiveness were drawn after the last emergence test (day 23). Acoustic startle responses were tested on day 24 post SD. Overall, SD rats as a group were not affected by the social conflict. Effects of SD seemed, however, to vary according to the behaviours that the intruder displayed during the social confrontation with the resident. Compared to those SD rats showing quick submission (SDS, n=5), SD rats fighting the resident during one or both SD confrontations before defeat (SDF, n=5) showed more fragmented slow wave sleep, both in SWS1 and SWS2. They also showed longer latency to leave the start box and spent less time in the open field arena compared to SDS rats. In the startle test, SDF rats failed to show response decrement at the lowest sound level. Our results indicate that how animals behave during a social confrontation is more important than exposure to the SD procedure itself, and that rapid submission during a social confrontation might be more adaptive than fighting back. Copyright © 2014 Elsevier Inc. All rights reserved.

Impairment of exploratory behavior and spatial memory in adolescent rats in lithium-pilocarpine model of temporal lobe epilepsy.

PubMed

Kalemenev, S V; Zubareva, O E; Frolova, E V; Sizov, V V; Lavrentyeva, V V; Lukomskaya, N Ya; Kim, K Kh; Zaitsev, A V; Magazanik, L G

2015-01-01

Cognitive impairment in six-week -old rats has been studied in the lithium-pilocarpine model of adolescent temporal lobe epilepsy in humans. The pilocarpine-treated rats (n =21) exhibited (a) a decreased exploratory activity in comparison with control rats (n = 20) in the open field (OP) test and (b) a slower extinction of exploratory behavior in repeated OP tests. The Morris Water Maze (MWM) test showed that the effect of training was less pronounced in the pilocarpine-treated rats, which demonstrated disruption of predominantly short-term memory. Therefore, our study has shown that lithium-pilocarpine seizures induce substantial changes in exploratory behavior and spatial memory in adolescent rats. OP and MWM tests can be used in the search of drugs reducing cognitive impairments associated with temporal lobe epilepsy.

Multi-walled carbon nanotubes increase anxiety levels in rats and reduce exploratory activity in the open field test.

PubMed

Sayapina, N V; Batalova, T A; Chaika, V V; Kuznetsov, V L; Sergievich, A A; Kolosov, V P; Perel'man, Yu M; Golokhvast, K S

2015-01-01

The results of the first study on the effects of multi-walled carbon nanotubes (MWNTs) on the exploratory activity and the emotional state in laboratory rats assessed by the open field test are reported. During three or ten days, rats received 8-10 nm MWNTs added to their food at a dose of 500 mg/kg. It was demonstrated that, in the group of rats which were fed with MWNTs, the integrated anxiety level index began to increase as early as the third day of the experiment; on the tenth day, it appeared to be twice increased. It was also demonstrated that MWNTs decreased the integrated exploratory activity index nearly twofold on the third day and nearly fourfold on the tenth day.

Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats

PubMed Central

Bruijnzeel, Adriaan W.; Qi, Xiaoli; Guzhva, Lidia V.; Wall, Shannon; Deng, Jie V.; Gold, Mark S.; Febo, Marcelo; Setlow, Barry

2016-01-01

Cannabis is the most widely used illicit drug in the world. Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component of cannabis and its effects have been well-studied. However, cannabis contains many other cannabinoids that affect brain function. Therefore, these studies investigated the effect of cannabis smoke exposure on locomotor activity, rearing, anxiety-like behavior, and the development of dependence in rats. It was also investigated if cannabis smoke exposure leads to tolerance to the locomotor-suppressant effects of the endogenous cannabinoid anandamide. Cannabis smoke was generated by burning 5.7% Δ9-THC cannabis cigarettes in a smoking machine. The effect of cannabis smoke on the behavior of rats in a small and large open field and an elevated plus maze was evaluated. Cannabis smoke exposure induced a brief increase in locomotor activity followed by a prolonged decrease in locomotor activity and rearing in the 30-min small open field test. The cannabinoid receptor type 1 (CB1) receptor antagonist rimonabant increased locomotor activity and prevented the smoke-induced decrease in rearing. Smoke exposure also increased locomotor activity in the 5-min large open field test and the elevated plus maze test. The smoke exposed rats spent more time in the center zone of the large open field, which is indicative of a decrease in anxiety-like behavior. A high dose of anandamide decreased locomotor activity and rearing in the small open field and this was not prevented by rimonabant or pre-exposure to cannabis smoke. Serum Δ9-THC levels were 225 ng/ml after smoke exposure, which is similar to levels in humans after smoking cannabis. Exposure to cannabis smoke led to dependence as indicated by more rimonabant-precipitated somatic withdrawal signs in the cannabis smoke exposed rats than in the air-control rats. In conclusion, chronic cannabis smoke exposure in rats leads to clinically relevant Δ9-THC levels, dependence, and has a biphasic effect on locomotor activity. PMID:27065006

Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats.

PubMed

Bruijnzeel, Adriaan W; Qi, Xiaoli; Guzhva, Lidia V; Wall, Shannon; Deng, Jie V; Gold, Mark S; Febo, Marcelo; Setlow, Barry

2016-01-01

Cannabis is the most widely used illicit drug in the world. Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component of cannabis and its effects have been well-studied. However, cannabis contains many other cannabinoids that affect brain function. Therefore, these studies investigated the effect of cannabis smoke exposure on locomotor activity, rearing, anxiety-like behavior, and the development of dependence in rats. It was also investigated if cannabis smoke exposure leads to tolerance to the locomotor-suppressant effects of the endogenous cannabinoid anandamide. Cannabis smoke was generated by burning 5.7% Δ9-THC cannabis cigarettes in a smoking machine. The effect of cannabis smoke on the behavior of rats in a small and large open field and an elevated plus maze was evaluated. Cannabis smoke exposure induced a brief increase in locomotor activity followed by a prolonged decrease in locomotor activity and rearing in the 30-min small open field test. The cannabinoid receptor type 1 (CB1) receptor antagonist rimonabant increased locomotor activity and prevented the smoke-induced decrease in rearing. Smoke exposure also increased locomotor activity in the 5-min large open field test and the elevated plus maze test. The smoke exposed rats spent more time in the center zone of the large open field, which is indicative of a decrease in anxiety-like behavior. A high dose of anandamide decreased locomotor activity and rearing in the small open field and this was not prevented by rimonabant or pre-exposure to cannabis smoke. Serum Δ9-THC levels were 225 ng/ml after smoke exposure, which is similar to levels in humans after smoking cannabis. Exposure to cannabis smoke led to dependence as indicated by more rimonabant-precipitated somatic withdrawal signs in the cannabis smoke exposed rats than in the air-control rats. In conclusion, chronic cannabis smoke exposure in rats leads to clinically relevant Δ9-THC levels, dependence, and has a biphasic effect on locomotor activity.

Maternal environment alters social interactive traits but not open-field behavior in Fischer 344 rats.

PubMed

Yamamuro, Yutaka

2008-10-01

Although it is recognized that the genetic background governs behavioral phenotypes, environmental factors also play a critical role in the development of various behavioral processes. The maternal environment has a major impact on pups, and the cross-fostering procedure is used to determine the influence of early life experiences. The present study examined the influence of maternal environment on behavioral traits in inbred Fischer 344 (F344) rats. F344/DuCrlCrlj and Wistar (Crlj:WI) pups were fostered from postnatal day 1 as follows: Wistar pups raised by Wistar dams, F344 raised by Wistar, Wistar raised by F344, and F344 raised by F344. At 10 weeks of age, rats were randomly assigned to an open-field test and social interaction test. In the open-field test, irrespective of the rearing conditions, the activity during the first 1 min was significantly lower in F344 rats than in Wistar rats. Latency to the onset of movement showed no difference between groups. In the social interaction test, the recognition performance during the first 1 min in F344 raised by F344 was significantly shorter than that in the other groups. The onset of recognition to a novel social partner in F344 raised by F344 was significantly delayed, and the delay disappeared upon cross-fostering by Wistar dams. These results raise the possibility that the behavioral phenotype of F344 rats results from the interplay of genetic factors and maternal environment during early life, and that F344 rats are a strain with high susceptibility to rearing conditions for the formation of their emotionality.

Examination of extremely low frequency electromagnetic fields on orthodontic tooth movement in rats

PubMed Central

Dogru, Mehmet; Akpolat, Veysi; Dogru, Arzum Guler; Karadede, Beyza; Akkurt, Atilim; Karadede, M. Irfan

2014-01-01

The purpose of this study was to evaluate whether 50 Hz extremely low frequency electromagnetic fields (ELF-EMFs) affect the amount of orthodontic tooth movement in rats. The experiments were performed on 18 male Sprague-Dawley rats. The rats were randomly divided into three groups (n = 6): cage-control (Cg-Cnt) group (n = 6); sinusoidal electromagnetic field (SEMF) group (n = 6); and pulsed electromagnetic field (PEMF) group (n = 6). In SEMF and PEMF groups, rats were subjected to 1.5 mT EMF exposure eight hours per day for eight days. In order to obtain tooth movement, holes were drilled on the right and left maxillary central incisors of the rats at a distance 1.5–2 mm away from the gingiva and 20 g of orthodontic forces were applied to the teeth. Generated linear model for repeated measures and Bonferroni tests were used to evaluate the differences between the groups. Interactions among groups by days were found by using Pillai's trace multivariate test. The results showed that significant differences were present among the groups (F = 5.035; p = 0.03) according to the extent of tooth movement. Significant differences between the amount of tooth movements were determined especially after the fifth day and the following days six, seven and eight (p < 0.001). Within the limitations, according to the results of the present study, the application of ELF-EMF accelerated the orthodontic tooth movement in rats. PMID:26019497

[Co-administration of RJR-2403 with low dose of 17beta-estradiol on spatial learning in ovariectomized rats].

PubMed

Fedotova, Yu O

2013-01-01

The aim of this work was to study the influence of stimulation or blockade Nalpha7-cholinoreceptors on dynamics of spatial learning in water Morris maze and on behavior in the "open field" test in adult ovariectomized (OVX) females given with a low dose of 17beta-estradiol. Agonist of Nalpha7-cholinoreceptors - RJR-2403 (1.0 mg/kg, i.p.) or antagonist of Nalpha7-cholinoreceptors - mecamylamine (1.0 mg/kg, i.p.) treated chronically (14 days) alone and in a combination with low dose of 17beta-estradiol (0.5 micro/rat, s.c.) to OVX rats. Co-administration of RJR-2403 with low dose of 17beta-estradiol completely restored impaired spatial learning in water Morris maze in OVX females. Moreover, OVX rats treated with RJR-2403 and low dose of 17beta-estradiol demonstrated increased exploratory and grooming behavior in the "open field" test. Both mecamylamine alone and in combination with low dose of 17beta-estradiol failed to influence on spatial learning and failed to modify behavior in the "open field" test in OVX rats. The results of the present study suggest a positive effect of RJR-2403 in combination with low dose of 17beta-estradiol on spatial learning at estrogen deficiency.

Impact of Acoustic Standing Waves on Structural Responses: Reverberant Acoustic Testing (RAT) vs. Direct Field Acoustic Testing (DFAT)

NASA Technical Reports Server (NTRS)

Kolaini, Ali R.; Doty, Benjamin; Chang, Zensheu

2012-01-01

Loudspeakers have been used for acoustic qualification of spacecraft, reflectors, solar panels, and other acoustically responsive structures for more than a decade. Limited measurements from some of the recent speaker tests used to qualify flight hardware have indicated significant spatial variation of the acoustic field within the test volume. Also structural responses have been reported to differ when similar tests were performed using reverberant chambers. To address the impact of non-uniform acoustic field on structural responses, a series of acoustic tests were performed using a flat panel and a 3-ft cylinder exposed to the field controlled by speakers and repeated in a reverberant chamber. The speaker testing was performed using multi-input-single-output (MISO) and multi-input-multi-output (MIMO) control schemes with and without the test articles. In this paper the spatial variation of the acoustic field due to acoustic standing waves and their impacts on the structural responses in RAT and DFAT (both using MISO and MIMO controls for DFAT) are discussed in some detail.

Anxiolytic effects of lavender oil inhalation on open-field behaviour in rats.

PubMed

Shaw, D; Annett, J M; Doherty, B; Leslie, J C

2007-09-01

To establish a valid animal model of the effects of olfactory stimuli on anxiety, a series of experiments was conducted using rats in an open-field test. Throughout, effects of lavender oil were compared with the effects of chlordiazepoxide (CDP), as a reference anxiolytic with well-known effects on open-field behaviour. Rats were exposed to lavender oil (0.1-1.0 ml) for 30 min (Experiment 1) or 1h (Experiment 2) prior to open-field test and in the open field or injected with CDP (10 mg/kg i.p.). CDP had predicted effects on behaviour, and the higher doses of lavender oil had some effects on behaviour similar to those of CDP. In Experiment 3, various combinations of pre-exposure times and amounts of lavender oil were used. With sufficient exposure time and quantity of lavender the same effects were obtained as in Experiment 2. Experiment 4 demonstrated that these behavioural effects of lavender could be obtained following pre-exposure, even if no oil was present in the open-field test. In Experiments 2-4, lavender oil increased immobility. Together, these experiments suggest that lavender oil does have anxiolytic effects in the open field, but that a sedative effect can also occur at the highest doses.

Hippocampus and cerebellum function following imipenem treatment in male and female rats: evaluation of sex differences during developmental stage.

PubMed

Golchin, Leila; Golchin, Lale; Vahidi, Ali Asghar; Shabani, Mohammad

2013-02-15

The B-Lactam antibiotics have been suggested to have some degree of neurotoxicity in experimental animals as well as in clinical situations. This study has been elucidated the alteration in hippocampal and cerebellum function following adolescent imipenem exposure in male and female rats. Hippocampus and cerebellum related behavioral dysfunction in imipenem -treated [intraperitoneally, 40 and 80 mg/kg/day for one week from 23-day-old] rats were analyzed using explorative, motor function, learning and memory tasks [grasping, rotarod, open field shuttle box and Morris water maze tests]. Exposure to imipenem especially in high dosage impaired the motor coordination in male and female rats. There weren't any differences in grasping time in male and female rats. When the rearing and grooming frequency of their recorded in open field test, both males and females were dramatically affected by exposure to imipenem. Compared to the saline, male and female rats trained one week after imipenem injection showed significant memory deficits in the shuttle box and Morris water maze tests. Results in this study suggested that animals treated with imipenem suffer from motor activity and cognitive impairment. However, hippocampal and cerebellum functions of male and female rats were profoundly affected by exposure to imipenem while no sex-differences in the most variable were evident.

Effects of 4-hydroxyisoleucine from Fenugreek Seeds on Depression-like Behavior in Socially Isolated Olfactory Bulbectomized Rats

PubMed Central

Kalshetti, Padmaja B.; Alluri, Ramesh; Mohan, Vishwaraman; Thakurdesai, Prasad Arvind

2015-01-01

Context: Antidepressant-like effects of (2S, 3R, 4S)-4-hydroxyisoleucine (4-HI), a major amino acid from fenugreek seeds, has been reported in the animal model of acute depression. Aims: To evaluate effects of subacute administration of 4-HI in animal model of stress-induced depression namely socially isolated olfactory bulbectomized rats. Materials and Methods: Bilateral olfactory bulbectomy (OBX) were induced in 30 Sprague-Dawley rats. After recovery period of 14 days, rats were randomized into five groups of 6 rats each and stressed with social isolation (individual housing). The rats were orally treated with either vehicle (OBX-Iso), positive control, fluoxetine (30 mg/kg) or 4-HI (10, 30, 100 mg/kg) once a day from day 14 onward. Separate group of rats with social isolation but without OBX (Sham-Iso) was also maintained. The behavioral depression and anxiety related parameters using open field test (OFT), sucrose intake test, novelty suppressed feeding (NSF) and forced swim test (FST), and neurochemical estimation (brain monoamines viz., serotonin and nor-adrenaline, serotonin turnover, and serum cortisol) were performed. Statistical Analysis Used: Data was analyzed by either two-way ANOVA (OFT and FST) or one-way ANOVA (sucrose intake test, NSF, and neurochemical estimation) followed by Dunnett's multiple comparisons test. Differences were considered significant at P < 0.05. Results: The significant and dose-dependent protection from behavioral and neurochemical changes were observed in 4-HI co-administrated OBX-Iso rats. Conclusion: 4-HI demonstrated the antidepressant and antianxiety effects in socially isolated stress-induced OBX rats with possible involvement of multiple stress relieving mechanisms. HIGHLIGHTS OF PAPER In this study, the subacute pretreatment of 4-HI showed strong and dose-dependent prevention of isolation stress related behavioral and neurochemical responses in olfactory bulbectomized rats. The prevention of hyperactive HPA axis in OBX-Iso stress-induced rats can be envisaged as probable mechanism of antidepressant and antianxiety effects of 4-HI. SUMMARY Effect of 4-hydroxyisoleucine (4-HI) in olfactory bulbectomized and socially isolated (Iso) rats was evaluated4-HI showed significant and dose-dependent antidepressant effects during novelty suppressed feeding (NSF) and forced swim test (FST)4-HI showed significant and dose-dependent antianxiety effects during OFT (open field test) and sucrose intake test4-HI showed protection from OBX-Iso stress-induced brain monoamines, serotonin turnover, and serum cortisol level elevation. Abbreviations used: SSRI: Selective Serotonin Reuptake Inhibitor; 4-HI: (2S, 3R, 4S)-4-hydroxyisoleucine; OBX: Olfactory bulbectomy; CPCSEA: Committee for the Purpose of Control and Supervision of Experiments on Animals; OFT: Open Field Test; NSF: Novelty Suppressed Feeding; FST: Forced Swimming Test; 5HT: 5-Hydroxytryptamine; 5-HIAA: 5-Hydroxyindoleacetic Acid; NA: Nor-adrenaline; and HPA: Hypothalamic-Pituitary Adrenal. PMID:26929572

The different effects of lithium and tamoxifen on memory formation and the levels of neurotrophic factors in the brain of male and female rats.

PubMed

Valvassori, Samira S; Borges, Cenita P; Varela, Roger B; Bavaresco, Daniela V; Bianchini, Guilherme; Mariot, Edemilson; Arent, Camila O; Resende, Wilson R; Budni, Josiane; Quevedo, João

2017-09-01

Lithium (Li) is a mood-stabilizing drug used in the treatment of bipolar disorder (BD). Recently, preclinical studies have demonstrated the potential of tamoxifen (TMX) in the treatment of acute episodes of BD. However, the prolonged use of TMX for mood disorders treatment is controversial. In this study, we evaluated the effects of TMX or Li on cognitive behavior, as well as the levels of neurotrophic factors in the brain of male and female rats. Male and female Wistar rats received administrations of water (control group), TMX or Li via gavage for a period of 28days; the rats were then subjected to the open-field test (to evaluate spontaneous locomotion), and the novel object recognition and step-down inhibitory avoidance tests (to evaluate cognition). The levels of NGF, BDNF and GDNF were evaluated in the hippocampus and frontal cortex of the subject rats. No significant differences were observed in the open-field and inhibitory avoidance tests after drug administration in either the male or female rats. The administration of TMX, but not Li, decreased the recognition index of both the male and female rats in the object recognition test. The chronic administration of TMX decreased, whereas Li increased the levels of BDNF in the hippocampus of both the male and female rats. Tamoxifen decreased the levels of NGF in the hippocampus of female rats. In conclusion, it can be suggested that long-term treatments with TMX can lead to significant cognitive impairments by reducing the levels of neurotrophic factors in the brain of rats. Copyright © 2017. Published by Elsevier Inc.

Alarm pheromone is detected by the vomeronasal organ in male rats.

PubMed

Kiyokawa, Yasushi; Kodama, Yuka; Kubota, Takahiro; Takeuchi, Yukari; Mori, Yuji

2013-10-01

It is widely known that a stressed animal releases specific pheromones, possibly for alarming nearby conspecifics. We previously investigated an alarm pheromone in male rats and found that this alarm pheromone evokes several responses, including increases in the defensive and risk assessment behaviors in a modified open-field test, and enhancement of the acoustic startle reflex. However, the role of the vomeronasal organ in these pheromone effects remains unclear. To clarify this point, vomeronasal organ-excising or sham surgeries were performed in male rats for use in 2 experimental models, after which they were exposed to alarm pheromone. We found that the vomeronasal organ-excising surgery blocked the effects of this alarm pheromone in both the modified open-field test and acoustic startle reflex test. In addition, the results of habituation/dishabituation test and soybean agglutinin binding to the accessory olfactory bulb suggested that the vomeronasal organ-excising surgery completely ablated the vomeronasal organ while preserving the functioning of the main olfactory system. From the above results, we showed that the vomeronasal organ plays an important role in alarm pheromone effects in the modified open-field test and acoustic startle reflex test.

Nonsocially housed rats (Ratus norvegicus) seek social interactions and social novelty more than socially housed counterparts.

PubMed

Templer, Victoria L; Wise, Taylor B; Dayaw, Katrina Isabel T; Dayaw, Judith Nicole T

2018-04-23

Sociability is the act or quality of social interaction and can be quantified by determining the number and duration of interactions with conspecifics. The purpose of this study was to examine the extent to which sustained social contact, as achieved by constant social living conditions, influenced social behavior. Beginning in juvenility, 19 male Long-Evans rats were housed in enriched environments, with half living socially in a large group and half living individually. After several months in these housing conditions, rats were tested on a sociality test and a social novelty preference test. Nonsocially housed rats exhibited more social behavior than socially housed rats. In the sociality test, nonsocially housed rats engaged with an unfamiliar rat more than socially housed rats. Similarly, in the social novelty test, nonsocially housed rats visited a novel stranger more than the now-familiar rat (from the sociality test) as compared with the socially housed rats. It is unlikely that general anxiety factors can account for between-groups social effects, as there were no group differences in behavior on the elevated zero maze and open field test. Furthermore, socially and nonsocially housed rats were matched in spontaneous object exploration and novelty preference in a novel object recognition test, eliminating the possibility that general exploratory behavior or novelty preference accounted for group differences in the sociability tasks. These results suggest that lack of social interaction in nonsocially housed rats may be more powerful for social motivation than the consistent opportunity for social contact afforded by social living conditions. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Behavioral differences between subgroups of rats with high and low threshold to clonic convulsions induced by DMCM, a benzodiazepine inverse agonist.

PubMed

Contó, Marcos Brandão; de Carvalho, José Gilberto Barbosa; Benedito, Marco Antonio Campana

2005-11-01

In epileptic patients, there is a high incidence of psychiatric comorbidities, such as anxiety. Gamma-aminobutyric acid (GABA) ionotropic receptor GABA(A)/benzodiazepine allosteric site is involved in both epilepsy and anxiety. This involvement is based on the fact that benzodiazepine allosteric site agonists are anticonvulsant and anxiolytic drugs; on the other hand, benzodiazepine inverse agonists are potent convulsant and anxiogenic drugs. The aim of this work was to determine if subgroups of rats selected according to their susceptibility to clonic convulsions induced by a convulsant dose 50% (CD50) of DMCM, a benzodiazepine inverse agonist, would differ in behavioral tests commonly used to measure anxiety (elevated plus-maze, open field) and depression (forced swimming test). In the first experiment, subgroups of adult male Wistar rats were selected after a single dose of DMCM and in the second experiment they were selected after two injections of DMCM given after an interval of 1 week. Those rats presenting full clonic convulsions were termed Low Threshold rats to DMCM-induced clonic convulsions (LTR) and those not having clonic convulsions High Threshold rats to DMCM-induced clonic convulsions (HTR). In both experiments, only those rats presenting full clonic convulsions induced by DMCM and those not showing any signs of motor disturbances were used in the behavioral tests. The results showed that the LTR subgroup selected after two injections of a CD50 of DMCM spent a significantly lower time in the open arms of the elevated plus-maze and in the off the walls area of the open field; moreover, this group also presented a higher number of rearings in the open field. There were no significant differences between HTR and LTR subgroups in the forced swimming test. LTR and HTR subgroups selected after only one injection of DMCM did not differ in the three behavioral tests. To verify if the behavioral differences between HTR and LTR subgroups of rats selected after two injections of DMCM were due to the clonic convulsion, another experiment was carried out in which subgroups of rats susceptible and nonsusceptible to clonic convulsions induced by a CD50 of picrotoxin, a GABA(A) receptor channel blocker, were selected and submitted to the elevated plus-maze and open field tests. The results obtained did not show any significant differences between these two subgroups in the elevated plus-maze and open field tests. In another approach to determine the relation between fear/anxiety and susceptibility to clonic convulsions, subgroups of rats were selected in the elevated plus-maze as more or less fearful/anxious. The CD50 for clonic convulsions induced by DMCM was determined for each of these two subgroups. The results showed a significantly lower CD50 for the more fearful/anxious subgroup, which means a higher susceptibility to clonic convulsions induced by DMCM. The present findings show a relation between susceptibility to clonic convulsions and fear/anxiety and vice versa which may be due to differences in the assembly of GABA(A)/allosteric benzodiazepine site receptors in regions of the brain.

Cognitive aspects of congenital learned helplessness and its reversal by the monoamine oxidase (MAO)-B inhibitor deprenyl

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schulz, D.; Schulz, D.; Mirrione, M.

2009-11-29

Cognitive processes are assumed to change with learned helplessness, an animal model of depression, but little is known about such deficits. Here we investigated the role of cognitive and related functions in selectively bred helpless (cLH, n = 10), non-helpless (cNLH, n = 12) and wild type (WT, n = 8) Sprague Dawley rats. The animals were exposed to an open field for 10 min on each of two test days. On the third day, an object exploration paradigm was carried out. The animals were later tested for helplessness. Both cLH and cNLH rats were more active than WTs onmore » the first day in the open field. Over trials, cNLH and WT rats lowered their activity less than cLH rats. This resistance-to-habituation co-varied with a resistance to develop helplessness. In cLH rats, higher 'anxiety' or less time spent in the center of the open field co-varied with severe helplessness. In WTs, a greater reactivity to novel objects and to a spatially relocated object predicted lower levels of helplessness. In cLH rats (n = 4-5 per group), chronic treatment with a high dose of the monoamineoxidase (MAO)-Binhibitordeprenyl (10 mg/kg; i.p.), an anti-Parkinson, nootropic and antidepressant drug, attenuated helplessness. Remarkably, helplessness reversal required the experience of repeated test trials, reminiscent of a learning process. Chronic deprenyl (10 mg/kg; i.p.) did not alter locomotion/exploration or 'anxiety' in the open field. In conclusion, helplessness may be related to altered mechanisms of reinforcement learning and working memory, and to abnormalities in MAO-A and/or MAO-B functioning.« less

Cognitive aspects of congenital learned helplessness and its reversal by the monoamine oxidase (MAO)-B inhibitor deprenyl.

PubMed

Schulz, Daniela; Mirrione, Martine M; Henn, Fritz A

2010-02-01

Cognitive processes are assumed to change with learned helplessness, an animal model of depression, but little is known about such deficits. Here we investigated the role of cognitive and related functions in selectively bred helpless (cLH, n=10), non-helpless (cNLH, n=12) and wild type (WT, n=8) Sprague Dawley rats. The animals were exposed to an open field for 10min on each of two test days. On the third day, an object exploration paradigm was carried out. The animals were later tested for helplessness. Both cLH and cNLH rats were more active than WTs on the first day in the open field. Over trials, cNLH and WT rats lowered their activity less than cLH rats. This resistance-to-habituation co-varied with a resistance to develop helplessness. In cLH rats, higher 'anxiety' or less time spent in the center of the open field co-varied with severe helplessness. In WTs, a greater reactivity to novel objects and to a spatially relocated object predicted lower levels of helplessness. In cLH rats (n=4-5 per group), chronic treatment with a high dose of the monoamine oxidase (MAO)-B inhibitor deprenyl (10mg/kg; i.p.), an anti-Parkinson, nootropic and antidepressant drug, attenuated helplessness. Remarkably, helplessness reversal required the experience of repeated test trials, reminiscent of a learning process. Chronic deprenyl (10mg/kg; i.p.) did not alter locomotion/exploration or 'anxiety' in the open field. In conclusion, helplessness may be related to altered mechanisms of reinforcement learning and working memory, and to abnormalities in MAO-A and/or MAO-B functioning. Copyright 2009 Elsevier Inc. All rights reserved.

Science Support Room Operations During Desert RATS 2009

NASA Technical Reports Server (NTRS)

Lofgren, G. E.; Horz, F.; Bell, M. S.; Cohen, B. A.; Eppler,D. B.; Evans, C. a.; Hodges, K. V.; Hynek, B. M.; Gruener, J. E.; Kring, D. A.;

The effects of gonadectomy and binge-like ethanol exposure during adolescence on open field behaviour in adult male rats.

PubMed

Yan, Wensheng; Kang, Jie; Zhang, Guoliang; Li, Shuangcheng; Kang, Yunxiao; Wang, Lei; Shi, Geming

2015-09-14

Binge drinking ethanol exposure during adolescence can lead to long-term neurobehavioural damage. It is not known whether the pubertal surge in testosterone that occurs during adolescence might impact the neurobehavioural effects of early ethanol exposure in adult animals. We examined this hypothesis by performing sham or gonadectomy surgeries on Sprague-Dawley rats around postnatal day (P) 23. From P28-65,the rats were administered 3.0g/kg ethanol using a binge-like model of exposure. Dependent measurements included tests of open field behaviour, blood ethanol concentrations, and testosterone levels. As adults, significant decreases in open field activity were observed in the GX rats. The open field behaviour of the GX rats was restored after testosterone administration. Binge-like ethanol exposure altered most of the parameters of the open field behaviour, suggestive of alcohol-induced anxiety, but rats treated with alcohol in combination with gonadectomy showed less motor behaviour and grooming behaviour and an increase in immobility, suggesting ethanol-induced depression. These results indicated that testosterone is required for ethanol-induced behavioural changes and that testicular hormones are potent stimulators of ethanol-induced behaviours. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Assessment of housing density, space allocation and social hierarchy of laboratory rats on behavioural measures of welfare.

PubMed

Barker, Timothy Hugh; George, Rebecca Peta; Howarth, Gordon Stanley; Whittaker, Alexandra Louise

2017-01-01

Minimum space allowances for laboratory rats are legislated based on weight and stocking rates, with the understanding that increased housing density encourages crowding stress. However, there is little evidence for these recommendations, especially when considering positive welfare outcomes. This study consisted of two experiments which investigated the effects of housing density (rats per cage), space allocation (surface area per rat) and social rank (dominance hierarchy) on the ability to perform simple behavioural tests. Male Sprague Dawley (SD) rats (n = 64) were allocated to either high-density (n = 8) or low-density (n = 8) cages. The second experiment investigated the effects of surface area. SD rats (n = 40) were housed in dyads in either the large (n = 10) or small (n = 10) cage. In both experiments, animals were tested on a judgment bias paradigm, with their responses to an ambiguous stimulus being ascribed as optimistic or pessimistic. Animals were also tested on open-field, novel-object recognition and social-interaction tests. Recordings were taken from 1700-2100h daily for rat observation and social rank establishment. Dominant animals responded with significantly more optimistic decisions compared to subordinates for both the housing density (p<0.001) and space allocation (p = 0.0015) experiment. Dominant animals responded with increased social affiliative behaviours in the social-interaction test, and spent more time in the centre of the open-field test for both experiments. No significance was detected between housing density or space allocation treatments. These findings suggest that social rank is a significantly greater modifier of affective state than either housing density or space allocation. This finding has not yet been reported and suggests that future drafts of housing guidelines should consider animal social status in addition to floor space requirements.

Assessment of housing density, space allocation and social hierarchy of laboratory rats on behavioural measures of welfare

PubMed Central

George, Rebecca Peta; Howarth, Gordon Stanley; Whittaker, Alexandra Louise

2017-01-01

Minimum space allowances for laboratory rats are legislated based on weight and stocking rates, with the understanding that increased housing density encourages crowding stress. However, there is little evidence for these recommendations, especially when considering positive welfare outcomes. This study consisted of two experiments which investigated the effects of housing density (rats per cage), space allocation (surface area per rat) and social rank (dominance hierarchy) on the ability to perform simple behavioural tests. Male Sprague Dawley (SD) rats (n = 64) were allocated to either high-density (n = 8) or low-density (n = 8) cages. The second experiment investigated the effects of surface area. SD rats (n = 40) were housed in dyads in either the large (n = 10) or small (n = 10) cage. In both experiments, animals were tested on a judgment bias paradigm, with their responses to an ambiguous stimulus being ascribed as optimistic or pessimistic. Animals were also tested on open-field, novel-object recognition and social-interaction tests. Recordings were taken from 1700-2100h daily for rat observation and social rank establishment. Dominant animals responded with significantly more optimistic decisions compared to subordinates for both the housing density (p<0.001) and space allocation (p = 0.0015) experiment. Dominant animals responded with increased social affiliative behaviours in the social-interaction test, and spent more time in the centre of the open-field test for both experiments. No significance was detected between housing density or space allocation treatments. These findings suggest that social rank is a significantly greater modifier of affective state than either housing density or space allocation. This finding has not yet been reported and suggests that future drafts of housing guidelines should consider animal social status in addition to floor space requirements. PMID:28926644

Re-evaluation of the interrelationships among the behavioral tests in rats exposed to chronic unpredictable mild stress

PubMed Central

Hu, Congli; Luo, Ying; Wang, Hong; Kuang, Shengnan; Liang, Guojuan; Yang, Yang; Mai, Shaoshan; Yang, Junqing

2017-01-01

The chronic unpredictable mild stress model of depression has been widely used as an experimental tool to investigate human psychopathology. Our objective was to provide an update on the validity and reliability of the chronic unpredictable mild stress model, by analyzing the interrelationships among the indexes using stepwise discriminant analysis and Pearson correlation coefficient to examine the possible combinations. We evaluated the depressive rats in both the presence and the absence of chronic unpredictable mild stress, using weight change, percentage of sucrose preference, coat state, splash test, open-field test, elevated plus-maze test, forced swimming test, and Morris water maze test. The results showed that 6-week-long chronic unpredictable mild stress produces significant depression and anxiety-like behavior. The combination of body weight change, percentage of sucrose preference, coat state score, open-field score, grooming latency of splash test, immobility time in force swimming test, and platform crossing in the Morris water maze test can effectively discriminate between normal and chronic unpredictable mild stress rats. Strong interrelationships were noted among these indexes in both open-field test and elevated plus-maze test. In conclusion, there might be certain criteria for the combination of behavioral endpoints, which is advantageous to more effectively and reliably assess the chronic unpredictable mild stress induced depression model. PMID:28931086

Sudden death in epileptic rats exposed to nocturnal magnetic fields that simulate the shape and the intensity of sudden changes in geomagnetic activity: an experiment in response to Schnabel, Beblo and May

NASA Astrophysics Data System (ADS)

Persinger, M. A.; McKay, B. E.; O'Donovan, C. A.; Koren, S. A.

2005-03-01

To test the hypothesis that sudden unexplained death (SUD) in some epileptic patients is related to geomagnetic activity we exposed rats in which limbic epilepsy had been induced to experimentally produced magnetic fields designed to simulate sudden storm commencements (SSCs). Prior studies with rats had shown that sudden death in groups of rats in which epilepsy had been induced months earlier was associated with the occurrence of SSCs and increased geomagnetic activity during the previous night. Schnabel et al. [(2000) Neurology 54:903 908) found no relationship between SUD in human patients and geomagnetic activity. A total of 96 rats were exposed to either 500, 50, 10 40 nT or sham (less than 10 nT) magnetic fields for 6 min every hour between midnight and 0800 hours (local time) for three successive nights. The shape of the complex, amplitude-modulated magnetic fields simulated the shape and structure of an average SSC. The rats were then seized with lithium and pilocarpine and the mortality was monitored. Whereas 10% of the rats that had been exposed to the sham field died within 24 h, 60% of the rats that had been exposed to the experimental magnetic fields simulating natural geomagnetic activity died (P<.001) during this period. These results suggest that correlational analyses between SUD in epileptic patients and increased geomagnetic activity can be simulated experimentally in epileptic rats and that potential mechanisms might be testable directly.

Effects of caffeine on locomotor activity in streptozotocin-induced diabetic rats.

PubMed

Bădescu, S V; Tătaru, C P; Kobylinska, L; Georgescu, E L; Zahiu, D M; Zăgrean, A M; Zăgrean, L

2016-01-01

Diabetes mellitus modifies the expression of adenosine receptors in the brain. Caffeine acts as an antagonist of A1 and A2A adenosine receptors and was shown to have a dose-dependent biphasic effect on locomotion in mice. The present study investigated the link between diabetes and locomotor activity in an animal model of streptozotocin-induced diabetes, and the effects of a low-medium dose of caffeine in this relation. The locomotor activity was investigated by using Open Field Test at 6 weeks after diabetes induction and after 2 more weeks of chronic caffeine administration. Diabetes decreased locomotor activity (total distance moved and mobility time). Chronic caffeine exposure impaired the locomotor activity in control rats, but not in diabetic rats. Our data suggested that the medium doses of caffeine might block the A2A receptors, shown to have an increased density in the brain of diabetic rats, and improve or at least maintain the locomotor activity, offering a neuroprotective support in diabetic rats. Abbreviations : STZ = streptozotocin, OFT = Open Field Test.

Desert Rats 2010 Operations Tests: Insights from the Geology Crew Members

NASA Technical Reports Server (NTRS)

Bleacher, J. E.; Hurtado, J. M., Jr.; Young, K. E.; Rice, J.; Garry, W. B.; Eppler, D.

2011-01-01

Desert Research and Technology Studies (Desert RATS) is a multi-year series of tests of NASA hardware and operations deployed in the high desert of Arizona. Conducted annually since 1997, these activities exercise planetary surface hardware and operations in relatively harsh conditions where long-distance, multi-day roving is achievable. Such activities not only test vehicle subsystems, they also stress communications and operations systems and enable testing of science operations approaches that advance human and robotic surface exploration capabilities. Desert RATS 2010 tested two crewed rovers designed as first-generation prototypes of small pressurized vehicles, consistent with exploration architecture designs. Each rover provided the internal volume necessary for crewmembers to live and work for periods up to 14 days, as well as allowing for extravehicular activities (EVAs) through the use of rear-mounted suit ports. The 2010 test was designed to simulate geologic science traverses over a 14-day period through a volcanic field that is analogous to volcanic terrains observed throughout the Solar System. The test was conducted between 31 August and 13 September 2010. Two crewmembers lived in and operated each rover for a week with a "shift change" on day 7, resulting in a total of eight test subjects for the two-week period. Each crew consisted of an engineer/commander and an experienced field geologist. Three of the engineer/commanders were experienced astronauts with at least one Space Shuttle flight. The field geologists were drawn from the scientific community, based on funded and published field expertise.

[Effect of previous experience in reacting to a danger signal on "open field" behavior in the rat].

PubMed

Poltyreva, T E; Petrov, E S

1983-01-01

Modification of rats behaviour in an "hopen field" test was investigated, induced by an acoustic stimulus, previously subjected to conditioning in a shuttle chamber in experiments with possibility and impossibility of avoidance from electrical shock. It has been established that presentation of a stimulus having the meaning of a danger signal, in a new situation, significantly suppresses investigating behaviour of rats, whereas the stimulus which had not been subjected to conditioning exerts no marked effect on behaviour. The greatest suppression was observed in rats with "learned helplessness". This fact suggests that the degree of suppression of the behaviour in an open field in response to a danger signal, depends on the animal's previous experience in reacting to this signal.

Postnatal MK-801 treatment of female rats impairs acquisition of working memory, but not reference memory in an eight-arm radial maze; no beneficial effects of enriched environment.

PubMed

Nozari, Masoumeh; Mansouri, Farshad Alizadeh; Shabani, Mohammad; Nozari, Hojat; Atapour, Nafiseh

2015-07-01

Memory impairment has been documented in MK-801 (NMDA receptor antagonist) model of schizophrenia, but less is known on the rescue and/or differential effects of MK-801 on short- and long-term memories. We determined the effects of MK-801 treatment and/or enriched environment (EE) on acquisition of reference and working memory in developing rats. Female Wistar rats were injected with MK-801 (1 mg/kg) from postnatal days (P) 6-10. Task acquisition, working memory error (WME), and reference memory error (RME) were assessed in an eight-arm radial maze task. Behavioral performance of rats was also tested in an open field test before (P35-P40) and after (P65-P70) radial maze training to assess anxiety and locomotion. EE was applied from birth up to the end of experiments. MK-801 treatment did not influence task acquisition in the radial maze; however, by the end of training, MK-801-treated rats made significantly more WME, but not RME, compared to control rats. Ratio of WME to total error was also significantly higher in MK-801 group. EE prevented MK-801-associated behaviors in the open field but did not exert beneficial effects on working memory deficit in the radial maze task. EE per se affected behavioral performance of rats only in the open field test. Our results suggest that postnatal MK-801 treatment differentially affects working and reference memory in a young brain. Anxiety and hyperactivity associated with MK-801 are observed more severely in adulthood. Dissociation of the positive effects of EE may suggest selective modification of distinct pathways.

[The influence of acute hypoxia on motility of rats in the open field test under the conditions of an altered photoperiod].

PubMed

Sopova, I Iu

2014-01-01

The influence of acute hypoxia on the motility of rats under the conditions of an altered photoperiod in the open field test was studied. Thus, keeping the animals in constant darkness after the modeling of acute hypoxia leads to the depression of locomotive and exploratory components of the behavior. At the same time the animals that were kept under the conditions of constant light show a change in the correlation between the components of motility after the action of hypoxia.

Early deprivation increases high-leaning behavior, a novel anxiety-like behavior, in the open field test in rats.

PubMed

Kuniishi, Hiroshi; Ichisaka, Satoshi; Yamamoto, Miki; Ikubo, Natsuko; Matsuda, Sae; Futora, Eri; Harada, Riho; Ishihara, Kohei; Hata, Yoshio

2017-10-01

The open field test is one of the most popular ethological tests to assess anxiety-like behavior in rodents. In the present study, we examined the effect of early deprivation (ED), a model of early life stress, on anxiety-like behavior in rats. In ED animals, we failed to find significant changes in the time spent in the center or thigmotaxis area of the open field, the common indexes of anxiety-like behavior. However, we found a significant increase in high-leaning behavior in which animals lean against the wall standing on their hindlimbs while touching the wall with their forepaws at a high position. The high-leaning behavior was decreased by treatment with an anxiolytic, diazepam, and it was increased under intense illumination as observed in the center activity. In addition, we compared the high-leaning behavior and center activity under various illumination intensities and found that the high-leaning behavior is more sensitive to illumination intensity than the center activity in the particular illumination range. These results suggest that the high-leaning behavior is a novel anxiety-like behavior in the open field test that can complement the center activity to assess the anxiety state of rats. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Strain, Sex, and Open-Field Behavior: Factors Underlying the Genetic Susceptibility to Helplessness

PubMed Central

Padilla, Eimeira; Barrett, Douglas W.; Shumake, Jason D.; Gonzalez-Lima, F.

2009-01-01

Learned helplessness represents a failure to escape after exposure to inescapable stress and may model human psychiatric disorders related to stress. Previous work has demonstrated individual differences in susceptibility to learned helplessness. In this study, we assessed different factors associated with this susceptibility, including strain, sex, and open-field behavior. Testing of three rat strains (Holtzman, Long-Evans, and Sprague-Dawley) revealed that Holtzman rats were the most susceptible to helplessness. Holtzman rats not only had the longest escape latencies following inescapable shock, but also showed spontaneous escape deficits in the absence of prior shock when tested with a fixed-ratio 2 (FR2) running response. Moreover, when tested with fixed-ratio 1 (FR1) running—an easy response normally unaffected by helplessness training in rats—inescapable shock significantly increased the escape latencies of Holtzman rats. Within the Holtzman strain, we confirmed recent findings that females showed superior escape performance and therefore appeared more resistant to helplessness than males. However, regression and covariance analyses suggest that this sex difference may be explained by more baseline ambulatory activity among females. In addition, some indices of novelty reactivity (greater exploration of novel vs. familiar open-field) predicted subsequent helpless behavior. In conclusion, Holtzman rats, and especially male Holtzman rats, have a strong predisposition to become immobile when stressed which interferes with their ability to learn active escape responses. The Holtzman strain therefore appears to be a commercially available model for studying susceptibility to helplessness in males, and novelty-seeking may be a marker of this susceptibility. PMID:19428642

A standardized extract of Ginkgo biloba prevents locomotion impairment induced by cassava juice in Wistar rats

PubMed Central

Rivadeneyra-Domínguez, Eduardo; Vázquez-Luna, Alma; Rodríguez-Landa, Juan F.; Díaz-Sobac, Rafael

2014-01-01

The long-term consumption of cassava (Manihot esculenta Crantz) juice produce neurotoxic effects in the rat, characterized by an increased motor activity in the open field test and presence of uncoordinated swim (i.e., lateral swimming), in the swim test; which has been associated with damage in the hippocampus (CA1). On the other hand, flavonoids content in the Ginkgo biloba extract has been reported to produces neuroprotective effects at experimental level; therefore we hypothesized that G. biloba extract may prevents the motor alterations produced by cassava juice and reduce cellular damage in hippocampal neurons of the rat. In present study the effect of vehicle, cassava juice (linamarin, 0.30 mg/kg), G. biloba extract (dry extract, 160 mg/kg), and combination of treatment were evaluated in the open field and swim tests to identify locomotor and hippocampal alterations in adult male Wistar rats. All treatments were administered once per day, every 24 h, for 28 days, by oral rout. The effect was evaluated at 0, 7, 14, 21, and 28 days of treatment. The results show that cassava group from day 14 of treatment increase crossing and rearing in the open field test, as compared with the vehicle group; while in the swim test produces an uncoordinated swim characterized by the lateral swim. In this same group an increase in the number of damage neurons in the hippocampus (CA1) was identified. Interestingly, both behavioral and neuronal alterations produced by cassava juice administration were prevented by treatment with G. biloba extract. The results shown that G. biloba extract exert a protective effect against behavioral and neuronal damage associated with consumption of cassava juice in the rat. These effects are possibly related with flavonoid content in the G. biloba extract. PMID:25309441

Evaluation of the biological tolerability of the starch-based medical device 4DryField® PH in vitro and in vivo a rat model.

PubMed

Poehnert, Daniel; Abbas, Mahmoud; Maegel, Lavinia; Sambale, Franziska; Lavrentieva, Antonina; Kreipe, Hans-Heinrich; Klempnauer, Jürgen; Winny, Markus

2015-10-01

To evaluate in vitro cytotoxicity/biocompatibility as well as in vivo tolerability of the novel polysaccharide 4DryField® PH, certified for haemostasis and adhesion prevention. In vitro cytotoxicity/viability testing according to ISO EN 10,993 using murine and human tumour cell lines incubated with 4DryField® PH (PlantTec Medical GmbH). Using a rat model the impact of 4DryField® PH on animals viability and in vivo effects were macro- and micropathologically assessed. In vitro testing revealed no cytotoxic effect of 4DryField® PH nor enhancement of viability to tumour cell lines. In vivo viability of rats was unimpaired by 4DryField® PH. Bodyweight loss in animals with abdominal injury plus treatment with 4DryField® PH was in the range of controls and less than in injured rats without treatment. At day 7 after surgery no formation of adhesions, neither macroscopic nor histological remnants nor signs of foreign body reaction were present in animals without injury. In animals with peritoneal injury and 4DryField® PH application, histopathological observation revealed minor residuals of polysaccharide in the depth of wound cavity embedded in a thickened subperitoneal layer; however, with a suggested intact neoperitoneum. The presence of mononuclear cells surrounding polysaccharide particles in varying states of degradation was observable as well. 4DryField® PH is not cytotoxic and does not enhance viability of tumour cell lines. High dose of 4DryField® PH of 1.09 g/kg bodyweight is well tolerated and reduces weight loss in animals with peritoneal injury. The biocompatibility of 4DryField® PH can be rated as being excellent. © The Author(s) 2015.

Desert Research and Technology Study 2003 Trip Report/ICES Paper

NASA Technical Reports Server (NTRS)

Ross, Amy; Kosmo, Joseph J.; Janoiko, Barbara; Eppler, Dean

2004-01-01

The Advanced Extra-vehicular Activity (EVA) team of the National Aeronautics and Space Administration (NASA) Johnson Space Center (JSC) Crew and Thermal Systems Division (CTSD) participated in the Desert Research and Technology Study (RATS) in September 2003, at Meteor Crater, AZ. The Desert RATS is an integrated remote field site te t with team members from several NASA centers (Johnson Space Center; Glenn and Ames Research Centers) and universities (Bowling Green State University, University of Cincinnati, Massachusetts Institute of Technology) participating. Each week of the two-week field test had a primary focus. The primary test hardware for the first week was the I-Gravity Lunar Rover Training Vehicle, or Grover, which was on loan to NASA from the United States Geological Survey (USGS) Astrogeology Research Program. The 2003 Grover driving test results serve as a rover performance characterization baseline for the Science, Crew, Operation and Utility Testbed (SCOUT) project team, which will be designing and fabricating a next generation roving vehicle prototype in Fiscal Year (FY) 2004. The second week of testing focused on EVA geologic traverses that utilized a geologic sample field analysis science trailer and also focused on human-robotic interaction between the suited subjects and the EVA Robotic Assistant (ERA). This paper will review the Advanced EVA team's role in the context of the overall Desert RATS, as well as the EVA team results and lessons learned. For information regarding other test participants' results, the authors can refer interested parties to the test reports produced by those Desert RATS teams.

Housing conditions influence motor functions and exploratory behavior following focal damage of the rat brain.

PubMed

Gornicka-Pawlak, Elzbieta; Jabłońska, Anna; Chyliński, Andrzej; Domańska-Janik, Krystyna

2009-01-01

The present study investigated influence of housing conditions on motor functions recovery and exploratory behavior following ouabain focal brain lesion in the rat. During 30 days post-surgery period rats were housed individually in standard cages (IS) or in groups in enriched environment (EE) and behaviorally tested. The EE lesioned rats showed enhanced recovery from motor impairments in walking beam task, comparing with IS animals. Contrarily, in the open field IS rats (both lesioned and control) traveled a longer distance, showed less habituation and spent less time resting at the home base than the EE animals. Unlike the EE lesioned animals, the lesioned IS rats, presented a tendency to hyperactivity in postinjury period. Turning tendency was significantly affected by unilateral brain lesion only in the EE rats. We can conclude that housing conditions distinctly affected the rat's behavior in classical laboratory tests.

Increased anxiety-like behaviour and altered GABAergic system in the amygdala and cerebellum of VPA rats - An animal model of autism.

PubMed

Olexová, Lucia; Štefánik, Peter; Kršková, Lucia

2016-08-26

Anxiety is one of the associated symptoms of autism spectrum disorder. According to the literature, increases in anxiety are accompanied by GABAergic system deregulation. The aim of our study, performed using an animal model of autism in the form of rats prenatally treated with valproic acid (VPA rats), was to investigate changes in anxiety-like behaviour and the gene expression of molecules that control levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain. Anxiety-like behaviours were investigated using zone preferences in the open field test. The levels of the 65 and 67kDa enzymes of l-glutamic acid decarboxylase (GAD) mRNAs and type 1 GABA transporter (GAT1) were evaluated in the amygdala, as well as GABA producing enzymes in the cortex layer of the cerebellum. Our research showed that adult VPA rats spent less time in the inner zone of the testing chamber and more time in the outer zone of the testing chamber in the open field test. We also found that adult VPA rats had increased expression of GAT1 in the amygdala, as well as decreased levels of GAD65 and GAD67 mRNA in the cerebellum compared to control animals. These findings support the existence of a relationship between increased anxiety-like behaviour and changes in the regulation of the GABAergic system in VPA rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of ELF magnetic fields on lipid peroxidation, sperm count, p53, and trace elements.

PubMed

Akdag, M Zulkuf; Dasdag, Suleyman; Aksen, Feyzan; Isik, Birgul; Yilmaz, Fahri

2006-11-01

Some epidemiological and laboratory studies suggest a possible connection between extremely low-frequency (ELF) magnetic fields and certain illnesses, such as cancer, immune suppression, as well as reproductive toxic effects and abnormalities. Therefore, the aim of this study was to investigate the effects of ELF magnetic fields (1.35 mT) on sperm count, malondialdehyde concentration, the histology of such organs as the testes, brain, liver, and kidney tissues, p53 immunoreactivity of bone marrow, and the serum concentrations of Cu2+, Zn2+, Mn2+, and Fe3+ in rats. Sixteen Sprague-Dawley male rats were divided into two groups. The rats in the experimental group were exposed to an ELF magnetic field 2 hr/day for 2 months (7 days a week). The rats in the control group were not exposed to the ELF magnetic field. The exposure was performed in a Faraday cage (130 x 65 x 80 cm) with grounded shielding against the electric component. The Mann-Whitney U-test was used for the statistical analysis of the data. Magnetic field measurements showed that, under the experimental conditions, the magnetic field-exposure system produced a stable flux density of 1.35+/-0.018 mT and a stable frequency of 50 Hz, with negligible harmonics and no transients. However, no statistically significant alteration was observed in the parameters measured in this study except in Mn2+ concentrations (p<0.001). The present study found no evidence of an adverse effect of ELF magnetic fields on the measured parameters except for significantly increased Mn2+ concentrations (p<0.001).

Chronic methylphenidate-effects over circadian cycle of young and adult rats submitted to open-field and object recognition tests.

PubMed

Gomes, Karin M; Souza, Renan P; Valvassori, Samira S; Réus, Gislaine Z; Inácio, Cecília G; Martins, Márcio R; Comim, Clarissa M; Quevedo, João

2009-11-01

In this study age-, circadian rhythm- and methylphenidate administration- effect on open field habituation and object recognition were analyzed. Young and adult male Wistar rats were treated with saline or methylphenidate 2.0 mg/kg for 28 days. Experiments were performed during the light and the dark cycle. Locomotor activity was significantly altered by circadian cycle and methylphenidate treatment during the training session and by drug treatment during the testing session. Exploratory activity was significantly modulated by age during the training session and by age and drug treatment during the testing session. Object recognition memory was altered by cycle at the training session; by age 1.5 h later and by cycle and age 24 h after the training session. These results show that methylphenidate treatment was the major modulator factor on open-field test while cycle and age had an important effect on object recognition experiment.

[Foshouningshen decoction improves sleeping via the serotonergic system in a rat model of insomnia].

PubMed

Huang, Jie-Cong; Xie, Wei; Deng, Ning; Liang, Wen-Lin; Hu, Dong-Rong; Hong, Yu; Zhou, Yang

2017-08-20

To evaluate the sedative and hypnotic effects of Foshouningshen decoction (FSNSD) and study its effects on expressions of 5-hydroxy tryptamine (5-HT) and 5-HT1A receptor (5-HT 1A R) in the hippocampus in a rat model of insomnia. Male KM mice were divided into control group, estazolam (0.4 mg/kg daily) group, and low-, moderate-, and high-dose FSNSD groups (daily dose of 12, 24, and 48 g/kg, respectively). After corresponding treatments for 1 week, the mice underwent sleep-inducing test with subthreshold and threshold doses of sodium pentobarbital. Forty-eight male SD rats were randomized into control group, insomnia model group, estazolam group (0.2 mg/kg daily), and low-, moderate-, and high-dose FSNSD groups (with daily dose of 6, 12, and 24 g/kg, respectively). Rat models of insomnia were established by intraperitoneal injection of 4-cholro-dl-phenylalanine (PCPA) at the daily dose of 350 mg/kg for 3 days, after which the rats received corresponding treatments via gavage for 1 week. The performance of the rats in open field test was recorded and the hippocampal expression of 5-HT was detected using ELISA; the expressions of 5-HT 1A R protein and mRNA in the hippocampus were detected using immunohistochemistry and real-time PCR, respectively. In the sleep-inducing test with a subthreshold dose of sodium pentobarbital, the mice treated with high-dose FSNSD showed a significantly higher rate of sleep onset than the control mice (P<0.05); in the test with a threshold dose of sodium pentobarbital, treatment with moderate- and high-dose FSNSD resulted in significantly prolonged sleeping time (P<0.01) and shortened sleep latency (P<0.05) in the mice. The rats in insomnia model group showed increased total distance in open field test (P<0.05) with significantly decreased content of 5-HT (P<0.01) and expressions of 5-HT 1A R protein and mRNA in the hippocampus (P<0.01). Treatment of the rats with estazolam or high-dose FSNSD obviously decreased the total distance in open field test (P<0.05) and increased the content of 5-HT (P<0.05) and expressions of 5-HT 1A R (P<0.01) in the hippocampus of rats with insomnia. FSNSD can produce therapeutic effects on insomnia possibly by increasing 5-HT content and expressions of 5-HT 1A R in the hippocampus.

Perinatal exposure to genistein, a soy phytoestrogen, improves spatial learning and memory but impairs passive avoidance learning and memory in offspring.

PubMed

Kohara, Yumi; Kuwahara, Rika; Kawaguchi, Shinichiro; Jojima, Takeshi; Yamashita, Kimihiro

2014-05-10

This study investigated the effects of perinatal genistein (GEN) exposure on the central nervous system of rat offspring. Pregnant dams orally received GEN (1 or 10 mg/kg/day) or vehicle (1 ml/kg/day) from gestation day 10 to postnatal day 14. In order to assess the effects of GEN on rat offspring, we used a battery of behavioral tests, including the open-field, elevated plus-maze, MAZE and step-through passive avoidance tests. MAZE test is an appetite-motivation test, and we used this mainly for assessing spatial learning and memory. In the MAZE test, GEN groups exhibited shorter latency from start to goal than the vehicle-treated group in both sexes. On the other hand, performances in the step-through passive avoidance test were non-monotonically inhibited by GEN in both sexes, and a significant difference was observed in low dose of the GEN-treated group compared to the vehicle-treated group in female rats. Furthermore, we found that perinatal exposure to GEN did not significantly alter locomotor activity or emotionality as assessed by the open-field and elevated-plus maze tests. These results suggest that perinatal exposure to GEN improved spatial learning and memory of rat offspring, but impaired their passive avoidance learning and memory. Copyright © 2014 Elsevier Inc. All rights reserved.

Tissue interactions with nonionizing electromagnetic fields. Final report, March 1979-February 1986

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adey, W.R.; Bawin, S.M.; Byus, C.V.

1986-08-01

This report provides an overview of this research program focused on basic research in nervous system responses to electric fields at 60 Hz. The emphasis in this project was to determine the fundamental mechanisms underlying some phenomena of electric field interactions in neural systems. The five studies of the initial program were tests of behavioral responses in the rat based upon the hypothesis that electric field detection might follow psychophysical rules known from prior research with light, sound and other stimuli; tests of electrophysiological responses to ''normal'' forms of stimulation in rat brain tissue exposed in vitro to electric fields,more » based on the hypothesis that the excitability of brain tissue might be affected by fields in the extracellular environment; tests of electrophysiological responses of spontaneously active pacemaker neurons of the Aplysia abdominal ganglion, based on the hypothesis that electric field interactions at the cell membrane might affect the balance among the several membrane-related processes that govern pacemaker activity; studies of mechanisms of low frequency electromagnetic field interactions with bone cells in the context of field therapy of ununited fractures; and manipulation of cell surface receptor proteins in studies of their mobility during EM field exposure.« less

Stress-induced behaviour in adult and old rats: effects of neonatal asphyxia, body temperature and chelation of iron.

PubMed

Rogalska, J; Caputa, M; Wentowska, K; Nowakowska, A

2006-11-01

Perinatal asphyxia in mammals leads to iron accumulation in the brain, which results in delayed neurobehavioural disturbances, including impaired learning and abnormal alertness over their entire life span. The aim of this investigation was to verify our hypothesis that newborn rats, showing reduced normal body temperature, are protected against neurotoxicity of the asphyxia up to senescence. Alertness was studied in adult and old male Wistar rats after exposure to critical neonatal anoxia: (i) at physiological neonatal body temperature of 33 degrees C, (ii) at body temperature elevated to 37 degrees C, or (iii) at body temperature elevated to 39 degrees C (the thermal conditions remained unchanged both during anoxia and for 2 h postanoxia). To elucidate the effect of iron-dependent postanoxic oxidative damage to the brain, half of the group (iii) was injected with deferoxamine, a chelator of iron. Postanoxic behavioural disturbances were recorded in open-field, elevated plus-maze, and sudden silence tests when the rats reached the age of 12 and 24 months. Open-field stress-induced motor activity was reduced in rats subjected to neonatal anoxia under hyperthermic conditions. In contrast, these rats were hyperactive in the plus-maze test. Both the plus-maze and sudden silence tests show reduced alertness of these rats to external stimuli signalling potential dangers. The behavioural disturbances were prevented by body temperature of 33 degrees C and by administration of deferoxamine.

Safety Evaluation of Self-assembling Peptide Gel after Intracranial Administration to Rats Using the Open Field Test.

PubMed

Tsunoda, Masashi; Sugaya, Chiemi; Sugiura, Yumiko; Nagai, Yusuke; Sakanishi, Kotaro

2016-01-01

Self-assembling peptides have been developed as clinical materials, which could scaffold to regenerate nerve cells and hemostatic materials in vivo. However, there has not been enough information for their in vivo application. The safety of self-assembling peptides for the application on the brain was examined using behavioral tests for each rat in this study. Self-assembling peptide gel was administered to the surface of the brain at a volume of 20 µL at 1.5%. After 2 months, the open field test and the prepulse inhibition (PPI) test were performed. There were no significant differences between the peptide gel and the control groups in locomotor distances and in %PPIs in the PPI test. The mean values of the percentage of time the rats stayed in the central area of the open field during the first 5 min and instances of center rearing or face washing in the peptide gel group were significantly higher than those in the control. There were amorphous substance in the subarachnoid region, and infiltrations of mononuclear cells were also observed in the self-assembling peptide gel group. Although the meaning of the effects observed in this study was not fully elucidated, the self-assembling gel produced marginal but significant behavioral and histological effects.

Effects of caffeine on locomotor activity in streptozotocin-induced diabetic rats

PubMed Central

Bădescu, SV; Tătaru, CP; Kobylinska, L; Georgescu, EL; Zahiu, DM; Zăgrean, AM; Zăgrean, L

2016-01-01

Diabetes mellitus modifies the expression of adenosine receptors in the brain. Caffeine acts as an antagonist of A1 and A2A adenosine receptors and was shown to have a dose-dependent biphasic effect on locomotion in mice. The present study investigated the link between diabetes and locomotor activity in an animal model of streptozotocin-induced diabetes, and the effects of a low-medium dose of caffeine in this relation. The locomotor activity was investigated by using Open Field Test at 6 weeks after diabetes induction and after 2 more weeks of chronic caffeine administration. Diabetes decreased locomotor activity (total distance moved and mobility time). Chronic caffeine exposure impaired the locomotor activity in control rats, but not in diabetic rats. Our data suggested that the medium doses of caffeine might block the A2A receptors, shown to have an increased density in the brain of diabetic rats, and improve or at least maintain the locomotor activity, offering a neuroprotective support in diabetic rats. Abbreviations: STZ = streptozotocin, OFT = Open Field Test PMID:27974933

Sex differences and the role of acute stress in the open-field tower maze.

PubMed

Lipatova, Olga; Campolattaro, Matthew M; Dixon, Dawndra C; Durak, Ayse

2018-05-15

Many studies provide evidence that differences in spatial learning exist between males and females. However, it is necessary to consider non-mnemonic factors that may influence these findings. The present experiment investigated acquisition, retention, and the effects of stress on response- and place-learning in male and female rats. Rats were trained in an open-field tower maze. Procedures were used to minimize stress in the rats, and their ability to solve place- or response-learning in the maze was determined by analyzing a response variable (i.e., first choice correct response) that was not influenced by general locomotor activity. The results revealed that male and female rats acquire place- and response-learning at the same rate even though females moved significantly faster in the maze. However, females showed better retrieval of place-, but not response-learning compared to male rats. This effect appeared to be enhanced when the rats were tested immediately following an acute restraint stress. Furthermore, both female and male rats that were exposed to acute restraint stress showed less impairment than controls when subsequently tested in a novel situation. These findings have clinical implications that a mild physiological stress response can make one more cognitively resistant to adversities later in life. Copyright © 2018 Elsevier Inc. All rights reserved.

Combined effects of complex magnetic fields and agmatine for contextual fear learning deficits in rats.

PubMed

McKay, B E; Persinger, M A

2003-04-18

Acute post-training exposures to weak intensity theta-burst stimulation (TBS) patterned complex magnetic fields attenuated the magnitude of conditioned fear learning for contextual stimuli. A similar learning impairment was evoked in a linear and dose-dependent manner by pre-conditioning injections of the polyamine agmatine. The present study examined the hypothesis that whole-body applications of the TBS complex magnetic field pattern when co-administered with systemic agmatine treatment may combine to evoke impairments in contextual fear learning. Within minutes of 4 mg/kg agmatine injections, male Wistar rats were fear conditioned to contextual stimuli and immediately exposed for 30 min to the TBS patterned complex magnetic field or to sham conditions. TBS patterned complex magnetic field treatment was found to linearly summate with the contextual fear learning impairment evoked by agmatine treatment alone. Furthermore, we report for sham-treated rats, but not rats exposed to the synthetic magnetic field pattern, that the magnitude of learned fear decreased and the amount of variability in learning increased, as the K-index (a measure of change in intensity of the time-varying ambient geomagnetic field) increased during the 3-hr intervals over which conditioning and testing sessions were conducted.

Failure to produce taste-aversion learning in rats exposed to static electric fields and air ions.

PubMed

Creim, J A; Lovely, R H; Weigel, R J; Forsythe, W C; Anderson, L E

1995-01-01

Taste-aversion (TA) learning was measured to determine whether exposure to high-voltage direct current (HVdc) static electric fields can produce TA learning in male Long Evans rats. Fifty-six rats were randomly distributed into four groups of 14 rats each. All rats were placed on a 20 min/day drinking schedule for 12 consecutive days prior to receiving five conditioning trials. During the conditioning trials, access to 0.1% sodium saccharin-flavored water was given for 20 min, followed 30 min later by one of four treatments. Two groups of 14 rats each were individually exposed to static electric fields and air ions, one group to +75 kV/m (+2 x 10(5) air ions/cm3) and the other group to -75 kV/m (-2 x 10(5) air ions/cm3). Two other groups of 14 rats each served as sham-exposed controls, with the following variation in one of the sham-exposed groups: This group was subdivided into two subsets of seven rats each, so that a positive control group could be included to validate the experimental design. The positive control group (n = 7) was injected with cyclophosphamide 25 mg/kg, i.p., 30 min after access to saccharin-flavored water on conditioning days, whereas the other subset of seven rats was similarly injected with an equivalent volume of saline. Access to saccharin-flavored water on conditioning days was followed by the treatments described above and was alternated daily with water "recovery" sessions in which the rats received access to water for 20 min in the home cage without further treatment. Following the last water-recovery session, a 20 min, two-bottle preference test (between water and saccharin-flavored water) was administered to each group. The positive control group did show TA learning, thus validating the experimental protocol. No saccharin-flavored water was consumed in the two-bottle preference test by the cyclophosphamide-injected, sham-exposed group compared to 74% consumed by the saline-injected sham-exposed controls (P < .0001). Saccharin-preference data for the static field-exposed groups showed no TA learning compared to data for sham-exposed controls. In summary, exposure to intense static electric fields and air ions did not produce TA learning as assessed by this particular design.

Rewiring the gustatory system: specificity between nerve and taste bud field is critical for normal salt discrimination.

PubMed

Spector, Alan C; Blonde, Ginger; Garcea, Mircea; Jiang, Enshe

2010-01-15

Forty years have passed since it was demonstrated that a cross-regenerated gustatory nerve in the rat tongue adopts the stimulus-response properties of the taste receptor field it cross-reinnervates. Nevertheless, the functional consequences of channeling peripheral taste signals through inappropriate central circuits remain relatively unexplored. Here we tested whether histologically confirmed cross-regeneration of the chorda tympani nerve (CT) into the posterior tongue in the absence of the glossopharyngeal nerve (GL) (CT-PostTongue) or cross-regeneration of the GL into the anterior tongue in the absence of the CT (GL-AntTongue) would maintain presurgically trained performance in an operant NaCl vs. KCl taste discrimination task in rats. Before surgery all groups were averaging over 90% accuracy. Oral amiloride treatment dropped performance to virtually chance levels. During the first week after surgery, sham-operated rats, GL-transected rats, and rats with regenerated CTs displayed highly competent discrimination performance. In contrast, CT-transected rats were severely impaired (59% accuracy). Both the CT-PostTongue and the GL-AntTongue groups were impaired to a similar degree as CT-transected rats. These initially impaired groups improved their performance over the weeks of postsurgical testing, suggesting that the rats were capable of relearning the task with discriminable signals in the remaining taste nerves. This relearned performance was dependent on input from amiloride-sensitive receptors likely in the palate. Overall, these results suggest that normal competence in a salt discrimination task is dependent on the taste receptor field origin of the input as well as the specific nerve transmitting the signals to its associated circuits in the brain. Copyright 2009 Elsevier B.V. All rights reserved.

[Effect of acute hypoxia on the intensity of free radical processes in the basal nuclei of the brain, and the rat behaviour in the open field test under conditions of altered photoperiod].

PubMed

Sopova, I Iu; Zamorskiĭ, I I

2011-03-01

The effect of acute hypoxia on the intensity of free radical processes in the basal nuclei (the nucleus caudatus, globus pallidus. nucleus accumbens. amygdaloid complex) of the brain, and the rat behaviour in the open field test has been studied under conditions of altered photoperiod. It has been shown that constant darkness levels the effect of acute hypoxia on the intensity of lipid peroxidation, preserves the activity of superoxide dismutase and catalase at a higher level, lowers the activity of glutathione peroxidase. Under light, the sensitivity of basal nuclei neurons to acute hypoxia is enhanced, the latter being reflected in intensification of lipid peroxidation at the expense of increased formation of dien conjugates. The activity of catalase at that considerably exceeds the level of even intact rats in all the structures. It has been established that an altered photoperiod modulates the effect of acute hypoxia on the parameters of rat's activity in the open field, the character of their change depending on the nature of a photophase change.

Effects of Tianeptine on Adult Rats Following Prenatal Stress

PubMed Central

Lee, Hwayoung; Kim, Hyung-Ki; Kwon, Jun-Tack; Kim, Young Ock; Seo, Jonghoon; Lee, Sanghyun; Cho, Ik-Hyun

2018-01-01

Objective Exposing a pregnant female to stress during the critical period of embryonic fetal brain development increases the risk of psychiatric disorders in the offspring. The objective of this study was to investigate the effect of antidepressant tianeptine on prenatally stressed (PNS) rats. Methods In this study, a repeated variable stress paradigm was applied to pregnant rats during the last week of gestation. To investigate the effects of antidepressant tianeptine on PNS rats, behavioral and protein expression analyses were performed. Forced swim test, open field test, and social interaction test were performed to determine changes in PNS rats compared to non-stressed offspring. Haloperidol was used as a positive control as an antipsychotic drug based on previous studies. Results Behavioral changes were restored after treatment with tianeptine or haloperidol. Western blot and immunohistochemical analyses of the prefrontal cortex revealed downregulation of several neurodevelopmental proteins in PNS rats. After treatment with tianeptine or haloperidol, their expression levels were increased. Conclusion Downregulation of several proteins in PNS rats might have caused subsequent behavioral changes in PNS rats. After tianeptine or haloperidol treatment, behavioral changes in PNS rats were restored. Therefore, tianeptine might decrease incidence of prenatal stress related-psychiatric disorders such as depression and schizophrenia. PMID:29739134

Gender differences in CMS and the effects of antidepressant venlafaxine in rats.

PubMed

Xing, Yanli; He, Jie; Hou, Jian; Lin, Fei; Tian, Jingwei; Kurihara, Hiroshi

2013-11-01

Gender differences in susceptibility to chronic mild stress (CMS) and effects of venlafaxine in rats have been investigated in the current study. Male and female SD rats were exposed to CMS or CMS plus chronic venlafaxine administration (10mg/kg, 21days) in order to study depressive behavior in rats. Rats were tested in open field test and sucrose preference test to figure out gender differences in behavior. Then serum corticosterone and the expression of FKBP5 in hippocampus of rats were detected to explore the possible mechanism. The results showed that the CMS impact on behavioral parameters and corticosterone levels and response to venlafaxine were gender dependent. Female rats appeared more vulnerable in the dysregulation of HPA axis to CMS. Venlafaxine treatment normalized depressive-like behavior in both gender. However, venlafaxine treated male rats exhibited better improved explore behavior and anhedonia. FKBP5 might be involved in the explanation of gender differences in CMS and venlafaxine treatment. Male and female rats respond differently to chronic stress and venlafaxine continuous treatment. This results have guiding meaning in design of trials related to stress induced depression. Copyright © 2013 Elsevier Ltd. All rights reserved.

Piracetam and vinpocetine ameliorate rotenone-induced Parkinsonism in rats.

PubMed

Zaitone, Sawsan A; Abo-Elmatty, Dina M; Elshazly, Shimaa M

2012-01-01

To evaluate the neuroprotective effect of the nootropic drugs, piracetam (PIR) and vinpocetine (VIN), in rotenone-induced Parkinsonism in rats. Sixty male rats were divided into 6 groups of 10 rats each. The groups were administered vehicle, control (rotenone, 1.5 mg/kg/48 h/6 doses, s.c.), PIR (100 and 200 mg/kg/day, p.o.) and VIN (3 and 6 mg/kg/day, p.o.). The motor performance of the rats was evaluated by the open field and pole test. Striatal dopamine level, malondialdehyde (MDA), reduced glutathione (GSH) and tumor necrosis factor-α (TNF-α) were assayed. Histopathological study of the substantia nigra was also done. Results showed that rotenone-treated rats exhibited bradykinesia and motor impairment in the open-field test. In addition, GSH level was decreased whereas MDA and TNF-α increased in striata of rotenone-treated rats as compared to vehicle-treated rats. Marked degeneration of the substantia nigra pars compacta (SNpc) neurons and depletion of striatal dopamine was also observed in the rotenone-treated rats. Treatment with PIR or VIN significantly reversed the locomotor deficits and increased striatal dopamine level. Treatment with VIN significantly (P<0.05) reduced the striatal level of MDA and GSH in comparison to rotenone group whereas TNF-α production was found to be significantly decreased in PIR group (P<0.05). VIN and PIR exhibit neuroprotective activity in rotenone-induced Parkinsonism. Hence, these nootropic agents may be considered as possible candidates in the treatment of Parkinson's disease.

Hippocampus lipid peroxidation induced by residual oil fly ash intranasal instillation versus habituation to the open field.

PubMed

Zanchi, Ana Claudia; Saiki, Mitiko; Saldiva, Paulo Hilário Nascimento; Barros, Helena Maria Tannhauser; Rhoden, Claudia Ramos

2010-01-01

Epidemiological studies have demonstrated the adverse effects of particulate matter (PM) inhalation on the respiratory and cardiovascular systems. It has been reported that air pollution may affect the central nervous system and decrease cognitive function. In rats, residual oil fly ash (ROFA) instillation causes decreased motor activity and increased lipid peroxidation in the striatum and the cerebellum. Our objective was to determine whether chronic instillation of particles induces changes in learning and memory in rats and whether oxidants in the hippocampus may contribute to these adverse effects. Forty-five-day-old male Wistar rats were exposed to ROFA by intranasal instillation and were treated with N-acetylcysteine (NAC) at 150 mg/kg i.p. for 30 days. Control groups were exposed to ROFA, NAC, or neither. On days 1, 8, and 30 of the protocol, rats were submitted to the open field test to evaluate habituation. After the last open field session, the rats were killed by decapitation. The hippocampus was used to determine lipid peroxidation (LP) by the thiobarbituric acid-reactive substances test. ROFA instillation induced an increase in LP in the hippocampus compared to all treatment groups (p = .012). NAC treatment blocked these changes. All of the treatment groups presented a decrease in the frequency of peripheral walking (p = .001), rearing (p = .001), and exploration (p = .001) over time. Our study demonstrates that exposure to particles for 30 days and/or NAC treatment do not modify habituation to an open field, a simple form of learning and memory in rats, and that oxidative damage induced by ROFA does not modulate these processes.

Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats.

PubMed

Kawaguchi, Shinichiro; Kuwahara, Rika; Kohara, Yumi; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

2015-02-01

Nonylphenol ethoxylate (NPE) is a non-ionic surfactant, that is degraded to short-chain NPE and 4-nonylphenol (NP) by bacteria in the environment. NP, one of the most common environmental endocrine disruptors, exhibits weak estrogen-like activity. In this study, we investigated whether oral administration of NP (at 0.5 and 5 mg/kg doses) affects spatial learning and memory, general activity, emotionality, and fear-motivated learning and memory in male and female Sprague-Dawley (SD) rats. SD rats of both sexes were evaluated using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) that was used to assess spatial learning and memory. In the MAZE test, the time required to reach the reward in male rats treated with 0.5 mg/kg NP group and female rats administered 5 mg/kg NP was significantly longer than that for control animals of the corresponding sex. In other behavioral tests, no significant differences were observed between the control group and either of the NP-treated groups of male rats. In female rats, inner and ambulation values for animals administered 0.5 mg/kg NP were significantly higher than those measured in control animals in open-field test, while the latency in the group treated with 5 mg/kg NP was significantly shorter compared to the control group in step-through passive avoidance test. This study indicates that oral administration of a low-dose of NP slightly impairs spatial learning and memory performance in male and female rats, and alters emotionality and fear-motivated learning and memory in female rats only.

Neophobia in spontaneous hypertensive (SHR) and normotensive control (WKY) rats.

PubMed

Delini-Stula, A; Hunn, C

1985-03-01

Latency of approaching a novel object (white-colored cube) placed in an unfamiliar open field, duration of object exploration, ambulation, rearing, grooming, and defecation were investigated in spontaneous hypertensive rats (SHR), their genetic normotensive controls (WKY), and standard Laboratory rats of Wistar origin (Tif:RAIf). The parameters measured were taken as indices of fear due to novelty (neophobia). Remarkable differences in behavior of all three strains were observed. By comparison to RAIf and WKY rats, SHR showed decreased neophobia as reflected in the significantly shorter latency of approaching the object and enhanced ambulation and rearing activity in the open field. By comparison to RAIf rats SHR also showed reduced grooming and defecation. WKY rats distinguished themselves from both SHR and RAIf by almost total absence of all responses in this test situation. This behavioral suppression was antagonized by 7.5 mg/kg ip of chlordiazepoxide. The results of this study further support the notion that, by comparison to standard laboratory rats, both SHR and WKY rats show possible genetically determined, altered behaviors which are diametrically opposite to each other.

The anxiolytic activity of n-3 PUFAs enriched egg yolk phospholipids in rat behavioral studies.

PubMed

Rutkowska, M; Słupski, W; Trocha, M; Szandruk, M; Rymaszewska, J

2016-11-02

Phospholipids play an important role in the biochemical and physiological processes of cells. An association between disturbed phospholipids metabolism in neuronal tissue and anxiety it was shown. The aim of this study was to examine the anxiolytic properties of phospholipids obtained from a new generation of eggs enriched in n-3 PUFA and its effect on locomotor activity in rat behavioral studies N-3 PUFA-enriched egg yolk phospholipids ("super lecithin") were added to the standard feed. Rats were fed by chow without (control group) or with (experimental group) addition of phospholipids. After six weeks of supplementation, the effect of phospholipids on locomotor activity in the open field test and anxiolytic properties in elevated plus maze and Vogel conflict test were examined. In the open field test the total distance traveled in the experimental group was similar to the control group. In the elevated plus maze test a six weeks phospholipids' administration significantly prolonged the time spent on the open arms by rats from experimental group compared to control group. The number of entries into the open arms was also increased but the difference was not statistically significant. The number of punished drinking water in the Vogel conflict test increased significantly in experimental versus control group. The obtained results suggest that the phospholipids isolated from n-3 PUFA enriched egg yolk have a specific anxiolytic effect, without general sedative influence.

Effects on locomotion and memory in 2 models of cerebral hypoperfusion in male Wistar rats.

PubMed

Martínez-Díaz, J A; García, L I; Hernández, M E; Aranda-Abreu, G E

2015-09-01

Cerebral ischaemia is one of the most common neurological diseases worldwide. Its many sequelae range from motor and sensory symptoms to cognitive decline and dementia. Animal models of cerebral ischaemia/hypoperfusion elicit effects on long term memory; however, the effects of these procedures on short term memory are not clearly understood and effects induced by alternative hypoperfusion models are completely unknown. We evaluated the effects of 2 cerebral hyperperfusion models on memory in 3-month-old male rats. Episodic memory and working memory were assessed using the new object recognition test and the spontaneous alteration test, respectively. Neurological assessment was also performed, along with an open field test to evaluate locomotor activity. Rats in both hyperperfusion models displayed no cognitive changes. Rats with unilateral left-sided ligation plus temporary ligation of the right carotid tended to show slightly impaired performance on the new object recognition test on the second day after the procedure. In contrast, the group with permanent unilateral ligation tended to display alterations in working and episodic memory 9 days after the procedure, but they subsequently recovered. Despite these differences, both hypoperfusion groups displayed clear signs of motor impairment 2 days after the procedure, as reflected by their decreased locomotor activity during the open field test. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

What a Nostril Knows: Olfactory Nerve-Evoked AMPA Responses Increase while NMDA Responses Decrease at 24-h Post-Training for Lateralized Odor Preference Memory in Neonate Rat

ERIC Educational Resources Information Center

Yuan, Qi; Harley, Carolyn W.

2012-01-01

Increased AMPA signaling is proposed to mediate long-term memory. Rat neonates acquire odor preferences in a single olfactory bulb if one nostril is occluded at training. Memory testing here confirmed that only trained bulbs support increased odor preference at 24 h. Olfactory nerve field potentials were tested at 24 h in slices from trained and…

Montanoa frutescens and Montanoa grandiflora extracts reduce anxiety-like behavior during the metestrus-diestrus phase of the ovarian cycle in Wistar rats.

PubMed

Rodríguez-Landa, Juan Francisco; Vicente-Serna, Julio; Rodríguez-Blanco, Luis Alfredo; Rovirosa-Hernández, María de Jesús; García-Orduña, Francisco; Carro-Juárez, Miguel

2014-01-01

In previous studies, the anxiolytic-like effects of Montanoa tomentosa and Montanoa frutescens were reported in male rats, but the potential anxiolytic-like effects of Montanoa plants during the different phases of the ovarian cycle in rats remain to be explored. The anxiolytic-like effects of the aqueous crude extracts of M. frutescens (25 and 50 mg/kg) and M. grandiflora (25 and 50 mg/kg) in the elevated plus maze were investigated in Wistar rats during the estrous cycle and compared with 2 mg/kg diazepam as a reference anxiolytic drug. To investigate any motor effect (i.e., hyperactivity, no changes, or hypoactivity) associated with the treatments, the rats were evaluated in the open field test. The M. frutescens (25 and 50 mg/kg) and M. grandiflora (50 mg/kg) extracts exerted anxiolytic-like effects during the metestrus-diestrus phase, similar to diazepam, without disrupting spontaneous motor activity. No significant effects of the extracts were detected in either behavioral test during the proestrus-estrus phase, whereas diazepam produced motor hypoactivity in the open field test. These results indicate that the M. frutescens and M. grandiflora extracts possess anxiolytic-like effects that depend on the ovarian cycle phase, supporting the Mexican ancient medicinal use of these plants to ameliorate anxiety disorders.

Montanoa frutescens and Montanoa grandiflora Extracts Reduce Anxiety-Like Behavior during the Metestrus-Diestrus Phase of the Ovarian Cycle in Wistar Rats

PubMed Central

Rodríguez-Landa, Juan Francisco; Vicente-Serna, Julio; Rodríguez-Blanco, Luis Alfredo; Rovirosa-Hernández, María de Jesús; García-Orduña, Francisco; Carro-Juárez, Miguel

2014-01-01

In previous studies, the anxiolytic-like effects of Montanoa tomentosa and Montanoa frutescens were reported in male rats, but the potential anxiolytic-like effects of Montanoa plants during the different phases of the ovarian cycle in rats remain to be explored. The anxiolytic-like effects of the aqueous crude extracts of M. frutescens (25 and 50 mg/kg) and M. grandiflora (25 and 50 mg/kg) in the elevated plus maze were investigated in Wistar rats during the estrous cycle and compared with 2 mg/kg diazepam as a reference anxiolytic drug. To investigate any motor effect (i.e., hyperactivity, no changes, or hypoactivity) associated with the treatments, the rats were evaluated in the open field test. The M. frutescens (25 and 50 mg/kg) and M. grandiflora (50 mg/kg) extracts exerted anxiolytic-like effects during the metestrus-diestrus phase, similar to diazepam, without disrupting spontaneous motor activity. No significant effects of the extracts were detected in either behavioral test during the proestrus-estrus phase, whereas diazepam produced motor hypoactivity in the open field test. These results indicate that the M. frutescens and M. grandiflora extracts possess anxiolytic-like effects that depend on the ovarian cycle phase, supporting the Mexican ancient medicinal use of these plants to ameliorate anxiety disorders. PMID:24800255

Anxiolytic-like effect of hydrogen sulfide (H2S) in rats exposed and re-exposed to the elevated plus-maze and open field tests.

PubMed

Donatti, Alberto Ferreira; Soriano, Renato Nery; Leite-Panissi, Christie Ramos Andrade; Branco, Luiz G S; de Souza, Albert Schiaveto

2017-03-06

Hydrogen sulfide (H 2 S), an endogenous gaseous mediator, modulates many physiological functions in mammals but evidence of its involvement in emotional and behavioral aspects is currently scarce. We hypothesized that this gas plays a modulatory role in behavioral parameters in rats submitted to tests (for 5min) in the open field (OF) and elevated plus-maze (EPM - test and retest). Male Wistar rats (200-250g) were intraperitoneally injected with saline or Na 2 S (a H 2 S donor; 4, 8 and 12mg/kg) either once or for 8days, and submitted to the OF test or to the EPM test and retest. A third group (naïve) was not injected but exposed to the same experimental protocols. In the OF test, Na 2 S injected for 8days caused a decrease in self-cleaning (4, 8 and 12mg/kg) and freezing behaviors (8 and 12mg/kg), and a rise in the rate of line crossings in the central part of the arena (12mg/kg). In the EPM test and retest, Na 2 S at 12mg/kg for 8days caused an increase in the number of open arm entries and in the percentage of time spent on open arms. Our data are consistent with the notion that H 2 S exerts anxiolytic-like effects in rats submitted to the EPM and OF tests. Moreover, this gaseous modulator reduces aversive learning in the EPM retest. Copyright © 2017 Elsevier B.V. All rights reserved.

Isolation and Molecular Characterization of Leptospira interrogans and Leptospira borgpetersenii Isolates from the Urban Rat Populations of Kuala Lumpur, Malaysia

PubMed Central

Benacer, Douadi; Zain, Siti Nursheena Mohd; Amran, Fairuz; Galloway, Renee L.; Thong, Kwai Lin

2013-01-01

Rats are considered the principal maintenance hosts of Leptospira. The objectives of this study were isolation and identification of Leptospira serovars circulating among urban rat populations in Kuala Lumpur. Three hundred urban rats (73% Rattus rattus and 27% R. norvegicus) from three different sites were trapped. Twenty cultures were positive for Leptospira using dark-field microscopy. R. rattus was the dominant carrier (70%). Polymerase chain reaction (PCR) confirmed that all isolates were pathogenic Leptospira species. Two Leptospira serogroups, Javanica and Bataviae, were identified using microscopic agglutination test (MAT). Pulsed-field gel electrophoresis (PFGE) identified two serovars in the urban rat populations: L. borgpetersenii serovar Javanica (85%) and L. interrogans serovar Bataviae (15%). We conclude that these two serovars are the major serovars circulating among the urban rat populations in Kuala Lumpur. Despite the low infection rate reported, the high pathogenicity of these serovars raises concern of public health risks caused by rodent transmission of leptospirosis. PMID:23358635

Piracetam and vinpocetine ameliorate rotenone-induced Parkinsonism in rats

PubMed Central

Zaitone, Sawsan A.; Abo-Elmatty, Dina M.; Elshazly, Shimaa M.

2012-01-01

Objective: To evaluate the neuroprotective effect of the nootropic drugs, piracetam (PIR) and vinpocetine (VIN), in rotenone-induced Parkinsonism in rats. Materials and Methods: Sixty male rats were divided into 6 groups of 10 rats each. The groups were administered vehicle, control (rotenone, 1.5 mg/kg/48 h/6 doses, s.c.), PIR (100 and 200 mg/kg/day, p.o.) and VIN (3 and 6 mg/kg/day, p.o.). The motor performance of the rats was evaluated by the open field and pole test. Striatal dopamine level, malondialdehyde (MDA), reduced glutathione (GSH) and tumor necrosis factor-α (TNF-α) were assayed. Histopathological study of the substantia nigra was also done. Results: Results showed that rotenone-treated rats exhibited bradykinesia and motor impairment in the open-field test. In addition, GSH level was decreased whereas MDA and TNF-α increased in striata of rotenone-treated rats as compared to vehicle-treated rats. Marked degeneration of the substantia nigra pars compacta (SNpc) neurons and depletion of striatal dopamine was also observed in the rotenone-treated rats. Treatment with PIR or VIN significantly reversed the locomotor deficits and increased striatal dopamine level. Treatment with VIN significantly (P < 0.05) reduced the striatal level of MDA and GSH in comparison to rotenone group whereas TNF-α production was found to be significantly decreased in PIR group (P < 0.05). Conclusion: VIN and PIR exhibit neuroprotective activity in rotenone-induced Parkinsonism. Hence, these nootropic agents may be considered as possible candidates in the treatment of Parkinson's disease. PMID:23248410

Neonatal tactile stimulation reverses the effect of neonatal isolation on open-field and anxiety-like behavior, and pain sensitivity in male and female adult Sprague-Dawley rats.

PubMed

Imanaka, A; Morinobu, S; Toki, S; Yamamoto, S; Matsuki, A; Kozuru, T; Yamawaki, S

2008-01-10

It is well known that early life events induce long-lasting psychophysiological and psychobiological influences in later life. In rodent studies, environmental enrichment after weaning prevents the adulthood behavioral and emotional disturbances in response to early adversities. We compared the behavioral effect of neonatal isolation (NI) with the effect of NI accompanied by tactile stimulation (NTS) to determine whether NTS could reverse or prevent the effects of NI on the adulthood behavioral and emotional responses to environmental stimuli. In addition, we also examined the sex difference of the NTS effect. Measurements of body weights, an open-field locomotor test, an elevated plus maze test, a hot-plate test, and a contextual fear-conditioning test were performed on postnatal day 60. As compared with rats subjected to NI, rats subjected to NTS showed significantly higher activity and exploration in the open-field locomotor test, lower anxiety-like behavior in the elevated plus maze test, and significantly prolonged latencies in the hot-plate test, and this effect was equal among males and females. In the contextual fear-conditioning test, whereas NTS significantly reduced the enhanced freezing time due to NI in females, no significant difference in the freezing time between NI and NTS was found in males. These findings indicate that adequate tactile stimulation in early life plays an important role in the prevention of disturbances in the behavioral and emotional responses to environmental stimuli in adulthood induced by early adverse experiences.

Acute and long-term consequences of single MDMA administration in relation to individual anxiety levels in the rat.

PubMed

Ho, Ying-Jui; Pawlak, Cornelius R; Guo, Lianghao; Schwarting, Rainer K W

2004-03-02

Our previous work has shown that normal male Wistar rats can differ systematically in their behavioral response to the elevated plus-maze (EPM), where animals with high (HA) or low anxiety (LA) levels can be identified based on the percentage of time spent in the open arms. These animals also differ in other behavioral tests (e.g. active avoidance), and in their serotonin levels in the ventral striatum. Here, we tested whether such HA and LA rats might respond differently to the amphetamine analogue 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). This drug can affect psychomotor activation and anxiety; effects which are probably due to its pronounced serotonergic and dopaminergic impacts in the rat brain. Based on a routine screening procedure in the plus-maze, male Wistar rats were divided into HA and LA sub-groups, in which rectal temperature was measured. Thirty minutes after the i.p. injection of MDMA (7.5 or 15 mg/kg) or vehicle, they were again tested in the plus-maze. During the next 3 weeks, the animals underwent further behavioral tests (plus-maze, open field, active avoidance, forced swimming) to test for possible long-term consequences of MDMA. Rectal temperature was found to be higher in LA than HA rats and was especially increased with the higher dose of MDMA (15 mg/kg). In the acute plus-maze test, the lower dose of MDMA led to an anxiogenic-like profile, whereas the higher dose led to an anxiolytic-like profile, both in HA and LA rats. Possible long-term consequences of MDMA were only tested with 7.5 mg/kg MDMA, since the 15 mg/kg dose led to a high level of lethality. The analysis of open field, plus-maze (performed after 9-12 days), and forced swimming behavior (performed after 20-21 days) did not provide indications for lasting effects of MDMA. In contrast, active avoidance learning was impaired in LA- but not HA-rats treated with MDMA. A single injection of MDMA does not only have acute effects on anxiety and psychomotor activation, but can also have some prolonged or delayed task-dependent behavioral consequences. The detection of such sequels can require that individual differences are taken into account and here, determining anxiety levels in the EPM seems to serve as a useful approach.

Daily maternal separations during stress hyporesponsive period decrease the thresholds of panic-like behaviors to electrical stimulation of the dorsal periaqueductal gray of the adult rat.

PubMed

Borges-Aguiar, Ana Cristina; Schauffer, Luana Zanoni; de Kloet, Edo Ronald; Schenberg, Luiz Carlos

2018-05-15

The present study examined whether early life maternal separation (MS), a model of childhood separation anxiety, predisposes to panic at adulthood. For this purpose, male pups were submitted to 3-h daily maternal separations along postnatal (PN) days of either the 'stress hyporesponsive period' (SHRP) from PN4 to PN14 (MS11) or throughout lactation from PN2 to PN21 (MS20). Pups were further reunited to conscious (CM) or anesthetized (AM) mothers to assess the effect of mother-pup interaction upon reunion. Controls were subjected to brief handling (15 s) once a day throughout lactation (BH20). As adults (PN60), rats were tested for the thresholds to evoke panic-like behaviors upon electrical stimulation of dorsal periaqueductal gray matter and exposed to an elevated plus-maze, an open-field, a forced swim and a sucrose preference test. A factor analysis was also performed to gain insight into the meaning of behavioral tests. MS11-CM rather than MS20-CM rats showed enhanced panic responses and reductions in both swimming and sucrose preference. Panic facilitations were less intense in mother-neglected rats. Although MS did not affect anxiety, MS11-AM showed robust reductions of defecation in an open-field. Factor analysis singled out anxiety, hedonia, exploration, coping and gut activity. Although sucrose preference and coping loaded on separate factors, appetite (adult weight) correlated with active coping in both forced swim and open-field (central area exploration). Concluding, whereas 3h-daily maternal separations during SHRP increased rat's susceptibility to experimental panic attacks, separations throughout lactation had no effects on panic and enhanced active coping. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of the aqueous extract of Pimpinella anisum L. seeds on exploratory activity and emotional behavior in rats using the open field and elevated plus maze tests.

PubMed

Gamberini, Maria Thereza; Rodrigues, Domingos Sávio; Rodrigues, Daniela; Pontes, Victoria Bottino

2015-06-20

Pimpinella anisum L. is considered one of the first plants used for medicinal purposes. Pharmacological actions of the plant on the central nervous system have been proven but previous analyses have focused on anticonvulsant and neuroprotective actions. In traditional medicine worldwide, the use of Pimpinella is commonly recommended as a tranquilizer, although no scientific information supporting this use is available. Therefore, it was decided to investigate the central actions of the plant to observe behavioral responses, with an emphasis on the emotional component. To investigate the effects of the aqueous extract of Pimpinella seeds on exploratory activity and emotional behavior in rats using the open field and elevated plus maze tests. Seeds of Pimpinella were extracted with distilled water, concentrated and freeze-dried yielding the aqueous extract(AE). Rats were divided into four groups: control(water 5 mL/kg, p.o.) and AE 0.5, 1.0 and 2.0 g/kg, p.o. Individual observations were performed in an open field and the parameters locomotor activity, rearing, grooming and defecation were recorded. In elevated plus maze test, rats were divided into four groups: control(water 5 mL/kg, p.o.) and AE 0.5, 1.0 and 2.0 g/kg, p.o. The parameters arm entries, total time spent in open and closed arms; and total number of arrivals at the end of an open or closed arm were recorded for each rat. Among the parameters assessed with the open field test, only rearing was reduced in the AE 0.5 g/kg group. When AE 1.0 g/kg was administered, only the initiation of exploratory activity was delayed, without impairing the animals' general activity. The highest dose of AE (2.0 g/kg) induced a reduction in the animals' habituation during the open field test within the same session, as evidenced by the maintenance of high levels of peripheral locomotion and rearing throughout the test. On the elevated plus maze test, no alterations were observed in the responses of the animals relative to controls for all doses tested. These results failed to support anxiety-related central action of the aqueous extract of Pimpinella seeds, invalidating popular beliefs regarding a tranquilizing effect. However, a habituation-related central action of the extract was demonstrated, suggesting action of bioactive compounds on central learning-related areas. The characterization of effects that may interfere with cognitive processes reinforces caution regarding indiscriminate consumption of the plant, especially in individuals with deficits, such as Alzheimer's Disease patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Extremely weak magnetic field exposure may inhibit hippocampal neurogenesis of Sprague Dawley rats

NASA Astrophysics Data System (ADS)

Zhang, B.; Tian, L.; Cai, Y.; Xu, H.; Pan, Y.

2016-12-01

Hippocampal neurogenesis occurs throughout life in mammals brains and can be influenced by animals' age as well as environmental factors. Lines of evidences have shown that the magnetic field is an important physics environmental factor influencing many animals' growth and development, and extremely weak magnetic field exposures have been proved having serious adverse effects on the metabolism and behaviors in some animals, but few studies have examined the response of hippocampal neurogenesis to it. In the present study, we experimentally examined the extremely weak magnetic field effects on neurogenesis of the dentate gyrus (DG) of hippocampus of adult Sprague Dawley (SD) rats. Two types of magnetic fields were used, an extremely weak magnetic field (≤ 0.5μT) and the geomagnetic fields (strength 31-58μT) as controls. Thirty-two SD rats (3-weeks old) were used in this study. New cell survival in hippocampus was assessed at 0, 14, 28, and 42 days after a 7-day intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Meanwhile, the amounts of immature neurons and mature neurons which are both related to hippocampal neurogenesis, as documented by labeling with doublecortin (DCX) and neuron (NeuN), respectively, were also analyzed at 0, 14, 28, and 42 days. Compared with geomagnetic field exposure groups, numbers of BrdU-, DCX-positive cells of DG of hippocampus in tested rats reduces monotonously and more rapidly after 14 days, and NeuN-positive cells significantly decreases after 28days when exposed in the extremely weak magnetic field condition. Our data suggest that the exposure to an extremely weak magnetic field may suppress the neurogenesis in DG of SD rats.

Assessment of Motor Function, Sensory Motor Gating and Recognition Memory in a Novel BACHD Transgenic Rat Model for Huntington Disease

PubMed Central

Abada, Yah-se K.; Nguyen, Huu Phuc; Schreiber, Rudy; Ellenbroek, Bart

2013-01-01

Rationale Huntington disease (HD) is frequently first diagnosed by the appearance of motor symptoms; the diagnosis is subsequently confirmed by the presence of expanded CAG repeats (> 35) in the HUNTINGTIN (HTT) gene. A BACHD rat model for HD carrying the human full length mutated HTT with 97 CAG-CAA repeats has been established recently. Behavioral phenotyping of BACHD rats will help to determine the validity of this model and its potential use in preclinical drug discovery studies. Objectives The present study seeks to characterize the progressive emergence of motor, sensorimotor and cognitive deficits in BACHD rats. Materials and Methods Wild type and transgenic rats were tested from 1 till 12 months of age. Motor tests were selected to measure spontaneous locomotor activity (open field) and gait coordination. Sensorimotor gating was assessed in acoustic startle response paradigms and recognition memory was evaluated in an object recognition test. Results Transgenic rats showed hyperactivity at 1 month and hypoactivity starting at 4 months of age. Motor coordination imbalance in a Rotarod test was present at 2 months and gait abnormalities were seen in a Catwalk test at 12 months. Subtle sensorimotor changes were observed, whereas object recognition was unimpaired in BACHD rats up to 12 months of age. Conclusion The current BACHD rat model recapitulates certain symptoms from HD patients, especially the marked motor deficits. A subtle neuropsychological phenotype was found and further studies are needed to fully address the sensorimotor phenotype and the potential use of BACHD rats for drug discovery purposes. PMID:23874679

The role of anxiety in vulnerability for self-injurious behaviour: studies in a rodent model.

PubMed

Yuan, X; Devine, D P

2016-09-15

Self-injurious behaviour (SIB) is a debilitating characteristic that is highly prevalent in autism and other neurodevelopmental disorders. Pathological anxiety is also common, and there are reports of comorbid anxiety and self-injury in some children. We have investigated potential interactions between anxiety and self-injury, using a rat model of pemoline-induced self-biting. In one experiment, rats were pre-screened for trait anxiety by measuring expression of anxiety-related behaviour on the elevated plus maze and open field emergence test. The rats were then treated with pemoline once daily for ten days, and vulnerability for pemoline-induced self-injury was evaluated. This revealed modest correlations between innate levels of anxiety-related behaviour in the open field test (time in the start box, and latency to enter the open field), and vulnerability for pemoline-induced self-biting (total duration of self-injurious oral contact, and total size of tissue injury). Measures in the elevated plus maze were not significantly correlated with vulnerability for pemoline-induced self-injury. In a second experiment, rats were treated with the beta-carboline FG 7142 twice daily, during 5days of treatment with pemoline. The rats that were treated with this anxiogenic drug exhibited greater duration of self-injurious oral contact, and larger injuries than vehicle-treated controls did. Overall, these results suggest that anxiety may contribute to the etiology and/or expression of self-injurious behaviour, and indicate that further research is warranted. Published by Elsevier B.V.

The point of entry contributes to the organization of exploratory behavior of rats on an open field: an example of spontaneous episodic memory.

PubMed

Nemati, Farshad; Whishaw, Ian Q

2007-08-22

The exploratory behavior of rats on an open field is organized in that animals spend disproportionate amounts of time at certain locations, termed home bases, which serve as centers for excursions. Although home bases are preferentially formed near distinctive cues, including visual cues, animals also visit and pause and move slowly, or linger, at many other locations in a test environment. In order to further examine the organization of exploratory behavior, the present study examined the influence of the point of entry on animals placed on an open field table that was illuminated either by room light or infrared light (a wavelength in which they cannot see) and near which, or on which, distinctive cues were placed. The main findings were that in both room light and infrared light tests, rats visited and lingered at the point of entry significantly more often than comparative control locations. Although the rats also visited and lingered in the vicinity of salient visual cues, the point of entry still remained a focus of visits. Finally, the preference for the point of entry increased as a function of salience of the cues marking that location. That the point of entry influences the organization of exploratory behavior is discussed in relation to the idea that the exploratory behavior of the rat is directed toward optimizing security as well as forming a spatial representation of the environment.

The effects of sexual experience and estrus on male-seeking motivated behavior in the female rat

PubMed Central

Nofrey, Barbara; Rocha, Beatriz; Lopez, Hassan H.; Ettenberg, Aaron

2008-01-01

Ovariectomized (OVX) female rats were trained to traverse a straight alley and return to a goal box where they had previously encountered a male rat, a female rat or an empty goal box. The time required to run the alley was used as an index of the subjects’ motivation to re-engage the goal box target. Subjects were tested in both estrus and non-estrus, first sexually naïve and then again after sexual experience. Female rats ran most quickly for a male target, most slowly for an empty goal box, and at intermediate speeds for a female target. Sexual experience tended to slow run times for all but male targets. Estrus enhanced approach behavior for males and an empty goal box, but tended to slow the approach toward females, both before and after sexual experience. This latter finding was further investigated in a second experiment in which sexually naïve OVX females were tested during estrus and non-estrus in a locomotor activity apparatus, a runway with an empty goal box, and an open field. Estrus produced no changes in spontaneous locomotion either in the activity box or the open field, but decreased run times in the alley and increased the number of center-square entries in the open-field. Thus, estrus produces increases in sexual motivation that selectively enhance exploratory, presumably male-seeking behavior, but not simple spontaneous locomotion. PMID:18761024

[Comparative study of the long-term behavioral effects of noopept and piracetam in adult male rats and female rats in postnatal period].

PubMed

Voronina, T A; Guzevatykh, L S; Trofimov, S S

2005-01-01

Adult male and female rats were treated with the peptide nootrope drug noopept (daily dose, 0.1 mg/kg) and piracetam (200 mg/kg). In the period from 8th to 20th day, both drugs (cognitive enhancers) suppressed the horizontal and vertical activity and the anxiety in test animals as compared to the control group treated with 0.9 % aqueous NaCl solution. Early postnatal injections of the nootropes influenced neither the morphology development nor the behavior of adult female rats in the plus maze, extrapolational escape, passive avoidance, and pain sensitivity threshold tests. Animals in the "intact" group (having received neither drugs not physiological solution, that is, developing in a poor sensor environment), showed less pronounced habituation in the open field test as compared to the control and drug treated groups.

Habitat Demonstration Unit-Deep Space Habitat (HDU-DSH) Integration and Preparation for Desert RATS 2011

NASA Technical Reports Server (NTRS)

Barbeau, Zack

2011-01-01

The Habitat Demonstration Unit, or HDU, is a multi-purpose test bed that allows NASA scientists and engineers to design, develop, and test new living quarters, laboratories, and workspaces for the next generation space mission. Previous testing and integration has occurred during 2010 at the annual Desert Research and Technology Studies (Desert RATS) field testing campaign in the Arizona desert. There the HDU team tests the configuration developed for the fiscal year, or FY configuration. For FY2011, the NASA mission calls for simulating a deep space condition. The HDU-DSH, or Deep Space Habitat, will be configured with new systems and modules that will outfit the test bed with new deep space capabilities. One such addition is the new X-HAB (eXploration Habitat) Inflatable Loft. With any deep space mission there is the need for safe, suitable living quarters. The current HDU configuration does not allow for any living space at all. In fact, Desert RATS 2010 saw the crew sleeping in the Space Exploration Vehicles (SEV) instead of the HDU. The X-HAB Challenge pitted three universities against each other: Oklahoma State University, University of Maryland, and the University of Wisconsin. The winning team will have their design implemented by NASA for field testing at DRATS 2011. This paper will highlight the primary objective of getting the X-HAB field ready which involves the implementation of an elevator/handrail system along with smaller logistical and integration tasks associated with getting the HDU-DSH ready for shipment to DRATS.

A study of the effect of a single neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") on the subsequent long-term behaviour of rats in the plus maze and open field.

PubMed

Mechan, Annis O; Moran, Paula M; Elliott, MartinJ; Young, Andrew J; Joseph, Michael H; Green, RichardA

2002-01-01

Decreased 5-HT function has been shown to induce behaviour consistent with an "anxiolytic" effect. Administration of a single dose of 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy" 12.5 mg/kg IP) to rats results in prolonged damage to central serotonergic nerve terminals. Thus we wished to assess whether an MDMA-induced lesion may have longer-term behavioural consequences. The study was designed to examine the behaviour of MDMA-pretreated and control animals in the elevated plus-maze and open field at a number of time-points, up to 80 days, after the administration of a single neurotoxic dose of MDMA (12.5 mg/kg IP). MDMA-pretreated Dark Agouti rats demonstrated a statistically significant reduction in anxiety-related behaviour, compared to saline-pretreated control rats, in both the elevated plus-maze and open field when the rats were tested on day 73 (open field) and day 80 (plus maze) after MDMA administration. The behavioural consequences of a single neurotoxic dose of MDMA can be demonstrated over 2 months after administration of the compound, thereby indicating that long-term adaptive changes occur within the brain following the neurodegeneration of 5-HT neurones produced by this recreationally used drug.

Chronic treatment with fluoxetine and sertraline prevents forced swimming test-induced hypercontractility of rat detrusor muscle.

PubMed

Bilge, Sirri; Bozkurt, Ayhan; Bas, Duygu B; Aksoz, Elif; Savli, Evren; Ilkaya, Fatih; Kesim, Yuksel

2008-01-01

Serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors represent important targets for the development of new treatments for detrusor overactivity and urinary incontinence. The present study was undertaken to investigate the effects of the forced swimming test (FST) on the contractile response of isolated rat detrusor muscle and to examine the effects of in vivo treatments of fluoxetine and sertraline on altered detrusor muscle contractility. Fluoxetine (20 mg/kg ip) and sertraline (10 mg/kg ip) were administered once a day for 14 days. Rats were exposed to the FST on the 15th day. After the test, detrusor muscles were removed and placed in organ baths, and the contraction responses induced by carbachol, potassium chloride (KCl) and electrical field stimulation (EFS) were recorded. The contractile responses of detrusor muscle strips to carbachol and electrical field stimulation were found to be increased at all carbachol doses and frequencies, respectively. FST also increased the contractile responses to KCl, which is used to test the differences in postreceptor-mediated contractions. The hypercontractile responses of detrusor strips to carbachol, EFS and KCl were abolished by treatment with both fluoxetine and sertraline. These treatments also decreased the immobility duration in the FST consistent with an antidepressant-like effect in this test. The results of this study provide the first evidence that FST increases contractility of the rat detrusor muscle, and this hypercontractility was abolished by chronic treatments of fluoxetine and sertraline at antidepressant doses by decreasing the postreceptor-mediated events.

Field Geologic Observation and Sample Collection Strategies for Planetary Surface Exploration: Insights from the 2010 Desert RATS Geologist Crewmembers

NASA Technical Reports Server (NTRS)

Hurtado, Jose M., Jr.; Young, Kelsey; Bleacher, Jacob E.; Garry, W. Brent; Rice, James W., Jr.

2012-01-01

Observation is the primary role of all field geologists, and geologic observations put into an evolving conceptual context will be the most important data stream that will be relayed to Earth during a planetary exploration mission. Sample collection is also an important planetary field activity, and its success is closely tied to the quality of contextual observations. To test protocols for doing effective planetary geologic field- work, the Desert RATS(Research and Technology Studies) project deployed two prototype rovers for two weeks of simulated exploratory traverses in the San Francisco volcanic field of northern Arizona. The authors of this paper represent the geologist crew members who participated in the 2010 field test.We document the procedures adopted for Desert RATS 2010 and report on our experiences regarding these protocols. Careful consideration must be made of various issues that impact the interplay between field geologic observations and sample collection, including time management; strategies relatedtoduplicationofsamplesandobservations;logisticalconstraintson the volume and mass of samples and the volume/transfer of data collected; and paradigms for evaluation of mission success. We find that the 2010 field protocols brought to light important aspects of each of these issues, and we recommend best practices and modifications to training and operational protocols to address them. Underlying our recommendations is the recognition that the capacity of the crew to flexibly execute their activities is paramount. Careful design of mission parameters, especially field geologic protocols, is critical for enabling the crews to successfully meet their science objectives.

Adolescent activity-based anorexia increases anxiety-like behavior in adulthood.

PubMed

Kinzig, Kimberly P; Hargrave, Sara L

2010-09-01

Activity-based anorexia is a paradigm that induces increased physical activity, reduced food intake, and heightened activity of the hypothalamic-pituitary-adrenal axis in adult rats. To investigate whether experience with activity-based anorexia produced enduring effects on brain and behavior, female adolescent rats experienced activity-based anorexia during adolescence and were tested in adulthood for anxiety-like behavior on an elevated plus maze and in an open field. Analysis of elevated plus maze and open field behavior in adulthood revealed that rats that experienced activity-based anorexia during adolescence, but not rats that were simply food restricted, displayed increased anxiety-like behavior in adulthood. Plasma corticosterone and expression levels of corticotropin-releasing hormone mRNA in the hypothalamic paraventricular nucleus and in the central nucleus of the amygdala were significantly elevated in adult rats that had undergone activity-based anorexia in adolescence in response to the open field exposure, as compared to control rats. These data demonstrate enduring effects of adolescent activity-based anorexia on anxiety-like behavior and neuroendocrine factors critical in stress responsivity in adulthood. Furthermore, we demonstrate that activity-based anorexia during adolescence serves as a model whereby prolonged anxiety is induced, allowing for evaluation of the behavioral and neural correlates of mediating anxiety-like behaviors in adulthood. Copyright 2010 Elsevier Inc. All rights reserved.

Adolescent Activity-Based Anorexia Increases Anxiety-Like Behavior in Adulthood

PubMed Central

Kinzig, Kimberly P.; Hargrave, Sara L.

2010-01-01

Activity-based anorexia is a paradigm that induces increased physical activity, reduced food intake, and heightened activity of the hypothalamic-pituitary-adrenal axis in adult rats. To investigate whether experience with activity-based anorexia produced enduring effects on brain and behavior, female adolescent rats experienced activity-based anorexia during adolescence and were tested in adulthood for anxiety-like behavior on an elevated plus maze and in an open field. Analysis of elevated plus maze and open field behavior in adulthood revealed that rats that experienced activity-based anorexia during adolescence, but not rats that were simply food restricted, displayed increased anxiety-like behavior in adulthood. Plasma corticosterone and expression levels of corticotropin- releasing hormone mRNA in the hypothalamic paraventricular nucleus and in the central nucleus of the amygdala were significantly elevated in adult rats that had undergone activity-based anorexia in adolescence in response to the open field exposure, as compared to control rats. These data demonstrate enduring effects of adolescent activity-based anorexia on anxiety-like behavior and neuroendocrine factors critical in stress responsivity in adulthood. Furthermore, we demonstrate that activity-based anorexia during adolescence serves as a model whereby prolonged anxiety is induced, allowing for evaluation of the behavioral and neural correlates of mediating anxiety-like behaviors in adulthood. PMID:20566408

Nootropic and anti-stress effects of rice bran oil in male rats.

PubMed

Mehdi, Bushra Jabeen; Tabassum, Saiqa; Haider, Saida; Perveen, Tahira; Nawaz, Amber; Haleem, Darakhshan Jabeen

2015-07-01

Rice bran oil (RBO) is an important product of rice bran. It is considered to be one of the most important nutritious oil due to its favorable fatty acid composition and unique composition of naturally occurring biologically active antioxidant compounds. This study was designed to monitor the effects of oral intake of RBO on stress response in rats. RBO was extracted using hexane. Rats were divided into Control and test (RBO-treated). RBO-treated rats were given 0.2 ml/day RBO for 6 weeks. Food intake and body weight changes were monitored weekly. After 6 weeks open field activity and Morris Water Maze (MWM) test were performed. Results showed that weekly cumulative food intake but not body weight were lower in RBO-treated rats during 1st to 5th week of treatment, which were normalized at the end of treatment. Exploratory activity of RBO-treated rats in an open field was increased. Spatial memory in Morris water maze was enhanced in RBO-treated than control rats. An episode of 2 h restraint stress decreased the 24 h food intake of both control and RBO-treated animals. Behavioral deficits were lower in RBO-treated rats. Exposure of 2 h restraint stress increased brain serotonin (5-hydroxytryptamine: 5-HT) metabolism. These increases were lower in RBO-treated restrained than their respective control animals. Serotonergic neurotransmitter mechanism is implicated in stress. The findings of the study show beneficial effects of RBO in learning and memory functions. Moreover, the study also highlights the attenuating effect of RBO on stress induced behavioral and neurochemical effects in rats.

Behavioral and genetic effects promoted by sleep deprivation in rats submitted to pilocarpine-induced status epilepticus.

PubMed

Matos, Gabriela; Ribeiro, Daniel A; Alvarenga, Tathiana A; Hirotsu, Camila; Scorza, Fulvio A; Le Sueur-Maluf, Luciana; Noguti, Juliana; Cavalheiro, Esper A; Tufik, Sergio; Andersen, Monica L

2012-05-02

The interaction between sleep deprivation and epilepsy has been well described in electrophysiological studies, but the mechanisms underlying this association remain unclear. The present study evaluated the effects of sleep deprivation on locomotor activity and genetic damage in the brains of rats treated with saline or pilocarpine-induced status epilepticus (SE). After 50 days of pilocarpine or saline treatment, both groups were assigned randomly to total sleep deprivation (TSD) for 6 h, paradoxical sleep deprivation (PSD) for 24 h, or be kept in their home cages. Locomotor activity was assessed with the open field test followed by resection of brain for quantification of genetic damage by the single cell gel electrophoresis (comet) assay. Status epilepticus induced significant hyperactivity in the open field test and caused genetic damage in the brain. Sleep deprivation procedures (TSD and PSD) did not affect locomotor activity in epileptic or healthy rats, but resulted in significant DNA damage in brain cells. Although PSD had this effect in both vehicle and epileptic groups, TSD caused DNA damage only in epileptic rats. In conclusion, our results revealed that, despite a lack of behavioral effects of sleep deprivation, TSD and PSD induced genetic damage in rats submitted to pilocarpine-induced SE. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Exposure to an open-field arena increases c-Fos expression in a distributed anxiety-related system projecting to the basolateral amygdaloid complex.

PubMed

Hale, M W; Hay-Schmidt, A; Mikkelsen, J D; Poulsen, B; Shekhar, A; Lowry, C A

2008-08-26

Anxiety states and anxiety-related behaviors appear to be regulated by a distributed and highly interconnected system of brain structures including the basolateral amygdala. Our previous studies demonstrate that exposure of rats to an open-field in high- and low-light conditions results in a marked increase in c-Fos expression in the anterior part of the basolateral amygdaloid nucleus (BLA) compared with controls. The neural mechanisms underlying the anatomically specific effects of open-field exposure on c-Fos expression in the BLA are not clear, however, it is likely that this reflects activation of specific afferent input to this region of the amygdala. In order to identify candidate brain regions mediating anxiety-induced activation of the basolateral amygdaloid complex in rats, we used cholera toxin B subunit (CTb) as a retrograde tracer to identify neurons with direct afferent projections to this region in combination with c-Fos immunostaining to identify cells responding to exposure to an open-field arena in low-light (8-13 lux) conditions (an anxiogenic stimulus in rats). Adult male Wistar rats received a unilateral microinjection of 4% CTb in phosphate-buffered saline into the basolateral amygdaloid complex. Rats were housed individually for 11 days after CTb injections and handled (HA) for 2 min each day. On the test day rats were either, 1) exposed to an open-field in low-light conditions (8-13 lux) for 15 min (OF); 2) briefly HA or 3) left undisturbed (control). We report that dual immunohistochemical staining for c-Fos and CTb revealed an increase in the percentage of c-Fos-immunopositive basolateral amygdaloid complex-projecting neurons in open-field-exposed rats compared with HA and control rats in the ipsilateral CA1 region of the ventral hippocampus, subiculum and lateral entorhinal cortex. These data are consistent with the hypothesis that exposure to the open-field arena activates an anxiety-related neuronal system with convergent input to the basolateral amygdaloid complex.

Neurotoxic behavioral effects of Lake Ontario salmon diets in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hertzler, D.R.

1990-03-01

Six experiments were conducted to examine possible neurotoxic effects of the exposure to contaminants in Lake Ontario salmon administered through the diets of rats. Rats were fed different concentrations of fish (8%, 15% or 30%) in one of three diet conditions: Lake Ontario salmon, Pacific Ocean salmon, or laboratory rat chow only. Following 20 days on the diets, rats were tested for five minutes per day in a modified open field for one or three days. Lake Ontario salmon diets consistently produced significantly lower activity, rearing, and nosepoke behaviors in comparison with ocean salmon or rat chow diet conditions. Amore » dose-response effect for concentration of lake salmon was obtained, and the attenuation effect occurred in males, females, adult or young animals, and postweaning females, with fish sampled over a five-year period. While only two of several potential contaminants were tested, both fish and brain analyses of mirex and PCBs relate to the behavioral effects.« less

Effects of prenatal stress on vulnerability to stress in prepubertal and adult rats.

PubMed

Fride, E; Dan, Y; Feldon, J; Halevy, G; Weinstock, M

1986-01-01

This study investigated the hypotheses that unpredictable prenatal stress has effects on the offspring, similar to those induced by perinatal administration of glucocorticoids and increases the vulnerability to stressful situations at adulthood. Rats were exposed to random noise and light stress throughout pregnancy. Offspring were tested for the development of spontaneous alternation behavior (SA) and at adulthood, their response to novel or aversive situations, open field, extinction and punishment following acquisition of an appetitive response and two-way active avoidance, were assessed. In prenatally stressed rats, the development of SA was significantly delayed. On repeated exposure to an open field they were less active; control rats had elevated plasma corticosterone (CCS) on days 2 and 4 of open field exposure, while prenatally stressed rats had significantly raised plasma CCS after each exposure (days 1-8). Furthermore, punishment-induced suppression of an appetitive response was enhanced. Acquisition of active avoidance was faciliated in female but reduced in male prenatally stressed offspring. It is suggested that random prenatal noise and light stress may cause impairment of development of hippocampal function which lasts into adulthood. This impairment is manifested as an increase in vulnerability and a decrease in habituation to stressful stimuli.

Tools and Technologies Needed for Conducting Planetary Field Geology While On EVA: Insights from the 2010 Desert RATS Geologist Crewmembers

NASA Technical Reports Server (NTRS)

Young, Kelsey; Hurtado, Jose M., Jr.; Bleacher, Jacob E.; Garry, W. Brent; Bleisath, Scott; Buffington, Jesse; Rice, James W., Jr.

2011-01-01

Observation is the primary role of all field geologists, and geologic observations put into an evolving conceptual context will be the most important data stream that will be relayed to Earth during a planetary exploration mission. Sample collection is also an important planetary field activity, and its success is closely tied to the quality of contextual observations. To test protocols for doing effective planetary geologic fieldwork, the Desert RATS (Research and Technology Studies) project deployed two prototype rovers for two weeks of simulated exploratory traverses in the San Francisco volcanic field of northern Arizona. The authors of this paper represent the geologist crewmembers who participated in the 2010 field test. We document the procedures adopted for Desert RATS 2010 and report on our experiences regarding these protocols. Careful consideration must be made of various issues that impact the interplay between field geologic observations and sample collection, including time management; strategies related to duplication of samples and observations; logistical constraints on the volume and mass of samples and the volume/transfer of data collected; and paradigms for evaluation of mission success. We find that the 2010 field protocols brought to light important aspects of each of these issues, and we recommend best practices and modifications to training and operational protocols to address them. Underlying our recommendations is the recognition that the capacity of the crew to "flexibly execute" their activities is paramount. Careful design of mission parameters, especially field geologic protocols, is critical for enabling the crews to successfully meet their science objectives.

[Electromagnetic Shielding Alters Behaviour of Rats].

PubMed

Temuryants, N A; Kostyuk, A S; Tumanyants, K N

2015-01-01

It has been found that long-term electromagnetic shielding (19 hours per day for 10 days) leads to an increase in the duration of passive swimming time in male rats, decrease the duration of active swimming in the "forced swim" test as well as decrease of libido. On the other hand animals kept under the "open field" conditions do not show significant deviations from their normal behavior. Therefore, one could conclude that moderate electromagnetic shielding causes a depression-like state in rats.

A weak magnetic field inhibits hippocampal neurogenesis in SD rats

NASA Astrophysics Data System (ADS)

Zhang, B.; Tian, L.; Cai, Y.; Pan, Y.

2017-12-01

Geomagnetic field is an important barrier that protects life forms on Earth from solar wind and radiation. Paleomagnetic data have well demonstrated that the strength of ancient geomagnetic field was dramatically weakened during a polarity transition. Accumulating evidence has shown that weak magnetic field exposures has serious adverse effects on the metabolism and behaviors in organisms. Hippocampal neurogenesis occurs throughout life in mammals' brains which plays a key role in brain function, and can be influenced by animals' age as well as environmental factors, but few studies have examined the response of hippocampal neurogenesis to it. In the present study, we have investigated the weak magnetic field effects on hippocampal neurogenesis of adult Sprague Dawley (SD) rats. Two types of magnetic fields were used, a weak magnetic field (≤1.3 μT) and the geomagnetic fields (51 μT).The latter is treated as a control condition. SD rats were exposure to the weak magnetic field up to 6 weeks. We measured the changes of newborn nerve cells' proliferation and survival, immature neurons, neurons and apoptosis in the dentate gyrus (DG) of hippocampus in SD rats. Results showed that, the weak magnetic field (≤1.3 μT) inhibited their neural stem cells proliferation and significantly reduced the survival of newborn nerve cells, immature neurons and neurons after 2 or 4 weeks continuous treatment (i.e. exposure to weak magnetic field). Moreover, apoptosis tests indicated the weak magnetic field can promote apoptosis of nerve cells in the hippocampus after 4 weeks treatment. Together, our new data indicate that weak magnetic field decrease adult hippocampal neurogenesis through inhibiting neural stem cells proliferation and promoting apoptosis, which provides useful experimental constraints on better understanding the mechanism of linkage between life and geomagnetic field.

A Novel Nonparametric Approach for Neural Encoding and Decoding Models of Multimodal Receptive Fields.

PubMed

Agarwal, Rahul; Chen, Zhe; Kloosterman, Fabian; Wilson, Matthew A; Sarma, Sridevi V

2016-07-01

Pyramidal neurons recorded from the rat hippocampus and entorhinal cortex, such as place and grid cells, have diverse receptive fields, which are either unimodal or multimodal. Spiking activity from these cells encodes information about the spatial position of a freely foraging rat. At fine timescales, a neuron's spike activity also depends significantly on its own spike history. However, due to limitations of current parametric modeling approaches, it remains a challenge to estimate complex, multimodal neuronal receptive fields while incorporating spike history dependence. Furthermore, efforts to decode the rat's trajectory in one- or two-dimensional space from hippocampal ensemble spiking activity have mainly focused on spike history-independent neuronal encoding models. In this letter, we address these two important issues by extending a recently introduced nonparametric neural encoding framework that allows modeling both complex spatial receptive fields and spike history dependencies. Using this extended nonparametric approach, we develop novel algorithms for decoding a rat's trajectory based on recordings of hippocampal place cells and entorhinal grid cells. Results show that both encoding and decoding models derived from our new method performed significantly better than state-of-the-art encoding and decoding models on 6 minutes of test data. In addition, our model's performance remains invariant to the apparent modality of the neuron's receptive field.

Effects of prolonged agmatine treatment in aged male Sprague-Dawley rats.

PubMed

Rushaidhi, M; Zhang, H; Liu, P

2013-03-27

Increasing evidence suggests that altered arginine metabolism contributes to cognitive decline during ageing. Agmatine, decarboxylated arginine, has a variety of pharmacological effects, including the modulation of behavioural function. A recent study demonstrated the beneficial effects of short-term agmatine treatment in aged rats. The present study investigated how intraperitoneal administration of agmatine (40mg/kg, once daily) over 4-6weeks affected behavioural function and neurochemistry in aged Sprague-Dawley rats. Aged rats treated with saline displayed significantly reduced exploratory activity in the open field, impaired spatial learning and memory in the water maze and object recognition memory relative to young rats. Prolonged agmatine treatment improved animals' performance in the reversal test of the water maze and object recognition memory test, and significantly suppressed age-related elevation in nitric oxide synthase activity in the dentate gyrus of the hippocampus and prefrontal cortex. However, this prolonged supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings further demonstrate that exogenous agmatine selectively improves behavioural function in aged rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

An investigation of Bartonella spp., Rickettsia typhi, and Seoul hantavirus in rats (Rattus spp.) from an inner-city neighborhood of Vancouver, Canada: is pathogen presence a reflection of global and local rat population structure?

PubMed

Himsworth, Chelsea G; Bai, Ying; Kosoy, Michael Y; Wood, Heidi; DiBernardo, Antonia; Lindsay, Robbin; Bidulka, Julie; Tang, Patrick; Jardine, Claire; Patrick, David

2015-01-01

Urban Norway and black rats (Rattus norvegicus and Rattus rattus) are reservoirs for variety of zoonotic pathogens. Many of these pathogens, including Rickettsia typhi, Bartonella spp., and Seoul hantavirus (SEOV), are thought to be endemic in rat populations worldwide; however, past field research has found these organisms to be absent in certain rat populations. Rats (Rattus spp.) from an inner city neighborhood of Vancouver, Canada, were tested for exposure to and/or infection with SEOV and R. typhi (using serology and PCR), as well as Bartonella spp. (using culture and sequencing). Approximately 25% of 404 rats tested were infected with Bartonella tribocorum, which demonstrated significant geographic clustering within the study area. Infection was associated with both season and sexual maturity. Seroreactivity against R. typhi and SEOV was observed in 0.36% and 1.45% of 553 rats tested, respectively, although PCR screening results for these pathogens were negative, suggesting that they are not endemic in the study population. Overall, these results suggest that the geographic distribution of rat-associated zoonoses, including R. typhi, SEOV, and Bartonella spp., is less ubiquitous than previously appreciated, and is likely dependent on patterns of dispersion and establishment of the rat reservoir host. Further study on global and local Rattus spp. population structures may help to elucidate the ecology of zoonotic organisms in these species.

[Open-field behavioral study in rat hyperlipidemia combined with chronic unpredictable mild stress model].

PubMed

Hu, Hua; Zhang, Yingchun; Xu, Yeqing; Liu, Chunfeng; Wang, Liwei

2015-06-16

To investigate behavioral changes in a rat hyperlipidemia model induced by high lipid feed combined with depression by Chronic Unpredictable Mild Stress (CUMS). A total of 40 rats were randomly divided into control (CON), control feed for 9 weeks followed by CUMS for 4 weeks (CON + CUMS), high fat diet (HFD) and high lipid feed for 9 weeks followed by CUMS for 4 weeks (HFD + CUMS) (n = 10 each). Open-field test was individually measured at baseline, week 9 and week 13. (1) Serum lipids: total cholesterol [(2.67 ± 0.04) mmol/L, (2.68 ± 0.02) mmol/L] and low density lipoprotein [(1.08 ± 0.03) mmol/L, (1.06 ± 0.01) mmol/L] of HFD and HFD + CUMS were both significantly higher than those of CON and CON + CUMS [(1.78 ± 0.12) mmol/L, (0.79 ± 0.04) mmol/L; (1.76 ± 0.09) mmol/L, (0.76 ± 0.06) mmol/L, all P < 0.01]. (2) Open-field test: at week 13, compared to CON rats, CON + CUMS rats exhibited enhanced locomotor activity during the first minute, reduced activity in the center squares and rearing, and increased the number of grooming and defecation (all P < 0.05). In comparison to the CON rats, a decrease in total squares in 5 min, central squares and peripheral squares was observed in HFD rats at week 13 (all P < 0.05). However, compared with HFD, CON, CON + CUMS rats, when high lipid feed for 9 weeks combined with depression, significant decrease activities in total squares in 5 min, central squares and peripheral squares were observed in HFD + CUMS rats at week 13. Besides these, the number of rearing was reduced, however, locomotor activity during the first minute and the number of grooming and defecation was significantly increased (all P < 0.001). Under uncontrolled hyperlipidemia, severe depressive symptoms will present more early once exposure to a series of chronic stressors followed by significant autonomic nervous dysfunctional symptoms.

Acute reversible inactivation of the bed nucleus of stria terminalis induces antidepressant-like effect in the rat forced swimming test

PubMed Central

2010-01-01

Background The bed nucleus of stria terminalis (BNST) is a limbic forebrain structure involved in hypothalamo-pituitary-adrenal axis regulation and stress adaptation. Inappropriate adaptation to stress is thought to compromise the organism's coping mechanisms, which have been implicated in the neurobiology of depression. However, the studies aimed at investigating BNST involvement in depression pathophysiology have yielded contradictory results. Therefore, the objective of the present study was to investigate the effects of temporary acute inactivation of synaptic transmission in the BNST by local microinjection of cobalt chloride (CoCl2) in rats subjected to the forced swimming test (FST). Methods Rats implanted with cannulae aimed at the BNST were submitted to 15 min of forced swimming (pretest). Twenty-four hours later immobility time was registered in a new 5 min forced swimming session (test). Independent groups of rats received bilateral microinjections of CoCl2 (1 mM/100 nL) before or immediately after pretest or before the test session. Additional groups received the same treatment and were submitted to the open field test to control for unspecific effects on locomotor behavior. Results CoCl2 injection into the BNST before either the pretest or test sessions reduced immobility in the FST, suggesting an antidepressant-like effect. No significant effect of CoCl2 was observed when it was injected into the BNST immediately after pretest. In addition, no effect of BNST inactivation was observed in the open field test. Conclusion These results suggest that acute reversible inactivation of synaptic transmission in the BNST facilitates adaptation to stress and induces antidepressant-like effects. PMID:20515458

Lessons Learned for Geologic Data Collection and Sampling: Insights from the Desert RATS 2010 Geologist Crewmembers

NASA Technical Reports Server (NTRS)

Hurtado, J. M., Jr.; Bleacher, J. E.; Rice, J.; Young, K.; Garry, W. B.; Eppler, D.

2011-01-01

Since 1997, Desert Research and Technology Studies (D-RATS) has conducted hardware and operations tests in the Arizona desert that advance human and robotic planetary exploration capabilities. D-RATS 2010 (8/31-9/13) simulated geologic traverses through a terrain of cinder cones, lava flows, and underlying sedimentary units using a pair of crewed rovers and extravehicular activities (EVAs) for geologic fieldwork. There were two sets of crews, each consisting of an engineer/commander and an experienced field geologist drawn from the academic community. A major objective of D-RATS was to examine the functions of a science support team, the roles of geologist crewmembers, and protocols, tools, and technologies needed for effective data collection and sample documentation. Solutions to these problems must consider how terrestrial field geology must be adapted to geologic fieldwork during EVAs

Genistein improves spatial learning and memory in male rats with elevated glucose level during memory consolidation.

PubMed

Kohara, Yumi; Kawaguchi, Shinichiro; Kuwahara, Rika; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

2015-03-01

Cognitive dysfunction due to higher blood glucose level has been reported previously. Genistein (GEN) is a phytoestrogen that we hypothesized might lead to improved memory, despite elevated blood glucose levels at the time of memory consolidation. To investigate this hypothesis, we compared the effects of orally administered GEN on the central nervous system in normal versus glucose-loaded adult male rats. A battery of behavioral assessments was carried out. In the MAZE test, which measured spatial learning and memory, the time of normal rats was shortened by GEN treatment compared to the vehicle group, but only in the early stages of testing. In the glucose-loaded group, GEN treatment improved performance as mazes were advanced. In the open-field test, GEN treatment delayed habituation to the new environment in normal rats, and increased the exploratory behaviors of glucose-loaded rats. There were no significant differences observed for emotionality or fear-motivated learning and memory. Together, these results indicate that GEN treatment improved spatial learning and memory only in the early stages of testing in the normal state, but improved spatial learning and memory when glucose levels increased during memory consolidation. Copyright © 2014 Elsevier Inc. All rights reserved.

Behavioural studies on BR-16A (Mentat), a herbal psychotropic formulation.

PubMed

Bhattacharya, S K

1994-01-01

The anxiolytic, antidepressant and anti-aggression activities of Mentat were investigated in rats and mice, using standard behavioural paradigms. Single acute administration of Mentat, up to a dose of 200 mg/kg, ip, induced insignificant behavioural effects on the test parameters. However, when Mentat was administered subchronically for 7 days at two dose levels (50 and 100 mg/kg, intragastrically), the drug induced dose-related behavioural effects. Thus, it exhibited anxiolytic effect, as assessed by paradigms like the open-field test and elevated plus-maze tests in mice, and the social interaction test and Vogel's drink conflict test in rats. Furthermore, Mentat attenuated the increase in rat brain tribulin, a putative endocoid marker of anxiety, levels induced by pentylenetetrazole (20 mg/kg, sc), a known anxiogenic agent. Mentat attenuated footshock-induced aggressive behaviour in paired rats but failed to affect clonidine-induced automutilative behaviour. The observed aggression-attenuating effect of Mentat may be related to its anxiolytic activity. Mentat exhibited significant antidepressant effect as indicated by its ability to reduce swim stress induced immobility in Porsolt's behavioural despair test, reduction in escape failures concomitant with an increase in avoidance response in the learned helplessness test, and attenuation of muricidal behaviour, in rats. The observed behavioural effects are consonant with the reported clinical utility of Mentat as an adjuvant in the treatment of anxiety and depression.

Behavioral reactions in rats exposed to low-energy laser radiation

NASA Astrophysics Data System (ADS)

Sieron, Aleksander; Mrowiec, Janina; Plech, Andrzej; Cieslar, Grzegorz; Biniszkiewicz, Tomasz

1995-03-01

The effect on their behavior of chronic exposure to infrared laser radiation applied to the skull of rats was evaluated. The experiment was carried out on 20 Wistar white male rats. A semiconductive infrared laser (wavelength -- 904 nm, frequency -- 100 Hz, pulse duration -- 10 ns, mean power 10 mW, energy density 1.5 J/cm2) was used. A skull fornix of rats was irradiated with use of multidiode probe, 10 minutes daily for 14 consecutive days. A locomotor activity was determined in the `open field' test. Simultaneously, an exploratory activity was examined in the `hole' test. Space memory was determined by means of a water maze test. Afterwards, an irritability was investigated by means of the score of Nakamura and Thoenen. The evaluation of behavior was made 24 hours after a single irradiation, at the 7th and 14th day of repeated everyday irradiation and then at the 7th and 14th day after the end of the cycle of irradiations. Obtained data show that low-energy laser radiation does not affect the rats central nervous system, resulting in persistent changes of behavior.

Mesenchymal stem cells restore orientation and exploratory behavior of rats after brain injury.

PubMed

Sokolova, I B; Fedotova, O R; Tsikunov, S G; Polyntsev, D G

2011-05-01

We studied the effects of intravenous and intracerebral transplantation of MSC on restoration of orientation and exploratory behavior of Wistar-Kyoto rats after removal of the left motor cortex. Removal of the motor cortex led to a significant reduction of the number of behavioral acts in the open field test. Two weeks after removal of the motor cortex and intravenous transplantation, the animals were as inhibited as the controls, but during the next 10 weeks, the behavioral status of these rats remained unchanged, while controls exhibited further behavioral degradation. After injection of MSC into the brain, the behavior of rats with trauma did not change in comparison with intact rats over 10 weeks.

Repeated exposure to corticosterone increases depression-like behavior in two different versions of the forced swim test without altering nonspecific locomotor activity or muscle strength.

PubMed

Marks, Wendie; Fournier, Neil M; Kalynchuk, Lisa E

2009-08-04

We have recently shown that repeated high dose injections of corticosterone (CORT) reliably increase depression-like behavior on a modified one-day version of the forced swim test. The main purpose of this experiment was to compare the effect of these CORT injections on our one-day version of the forced swim test and the more traditional two-day version of the test. A second purpose was to determine whether altered behavior in the forced swim test could be due to nonspecific changes in locomotor activity or muscle strength. Separate groups of rats received a high dose CORT injection (40 mg/kg) or a vehicle injection once per day for 21 consecutive days. Then, half the rats from each group were exposed to the traditional two-day forced swim test and the other half were exposed to our one-day forced swim test. After the forced swim testing, all the rats were tested in an open field and in a wire suspension grip strength test. The CORT injections significantly increased the time spent immobile and decreased the time spent swimming in both versions of the forced swim test. However, they had no significant effect on activity in the open field or grip strength in the wire suspension test. These results show that repeated CORT injections increase depression-like behavior regardless of the specific parameters of forced swim testing, and that these effects are independent of changes in locomotor activity or muscle strength.

Clinical doses of citalopram or reboxetine differentially modulate passive and active behaviors of female Wistar rats with high or low immobility time in the forced swimming test.

PubMed

Flores-Serrano, Ana Gisela; Vila-Luna, María Leonor; Álvarez-Cervera, Fernando José; Heredia-López, Francisco José; Góngora-Alfaro, José Luis; Pineda, Juan Carlos

2013-09-01

The sensitivity of immobility time (IT) to antidepressant-drugs differs in rats expressing high or low motor activity during the forced swimming test (FST). However, whether this heterogeneity is expressed after the administration of the most selective serotonin and norepinephrine reuptake inhibitors (SSRIs and SNRIs, respectively) is unknown. We compared the influence of either the SSRI citalopram or the SNRI reboxetine with the tricyclic antidepressant amitriptyline on two subgroups of female Wistar rats expressing high IT (HI; at or above the mean value) or low IT (LI; below the mean) during the initial 5 min of the first session of the FST. None of the tested drugs increased motor activity in the open field test. When vehicle was applied to either HI or LI rats, IT increased in the second session of the FST. This increment concurred with a simultaneous climbing time (CT) decrement. When amitriptyline (15 mg/kg) was tested the CT increased for both HI and LI rats. This increment was accompanied by an IT decrement in HI and LI rats. Reboxetine (0.16 or 1 mg/kg) precluded IT and CT changes in both HI and LI rats and produced a swimming time reduction. Citalopram (0.4, 1, and 3 mg/kg) essentially mimicked the influence of reboxetine on the IT and CT in LI rats, as well as in HI rats, but in the latter case only at 3 mg/kg. Yet, at the dose of 10 mg/kg citalopram lacked this effect in both subgroups. No differences were detected when the IT of LI rats was evaluated with citalopram (3 mg/kg) during estrus or diestrus stage. These results show that clinical doses of citalopram produced an antidepressant-like effect selectively in LI rats, while amitriptyline or reboxetine produced this effect in both LI and HI animals. Copyright © 2013 Elsevier Inc. All rights reserved.

Sex and repeated restraint stress interact to affect cat odor-induced defensive behavior in adult rats.

PubMed

Perrot-Sinal, Tara S; Gregus, Andrea; Boudreau, Daniel; Kalynchuk, Lisa E

2004-11-19

The overall objective of the present experiment was to assess sex differences in the effects of repeated restraint stress on fear-induced defensive behavior and general emotional behavior. Groups of male and female Long-Evans rats received either daily restraint stress (stressed) or daily brief handling (nonstressed) for 21 consecutive days. On days 22-25, a number of behavioral tests were administered concluding with a test of defensive behavior in response to a predatory odor. Stressed and nonstressed males and females were exposed to a piece of cat collar previously worn by a female domestic cat (cat odor) or a piece of collar never worn by a cat (control odor) in a familiar open field containing a hide barrier. Rats displayed pronounced defensive behavior (increased hiding and risk assessment) and decreased nondefensive behavior (grooming, rearing) in response to the cat odor. Nonstressed females exposed to cat odor displayed less risk assessment behavior relative to nonstressed males exposed to cat odor. Restraint stress had little effect on defensive behavior in male rats but significantly increased risk assessment behaviors in females. Behavior on the Porsolt forced swim test (a measure of depression-like behavior) and the open field test (a measure of anxiety-like behavior) was not affected by stress or sex. These findings indicate the utility of the predator odor paradigm in detecting subtle shifts in naturally occurring anxiety-like behaviors that may occur differentially in males and females.

Divergent stress responses and coping styles in psychogenetically selected Roman high-(RHA) and low-(RLA) avoidance rats: behavioural, neuroendocrine and developmental aspects.

PubMed

Steimer, Thierry; Driscoll, Peter

2003-06-01

The Swiss sublines of Roman high-(RHA/Verh) and low-(RLA/Verh) avoidance rats have been genetically selected for good vs. poor performance in two-way active avoidance since 1972. RLA/Verh rats show increased stress responses (e.g. freezing behaviour, ACTH, corticosterone and prolactin secretion) and adopt a more passive (or reactive) coping style when confronted with a novel environment. In the open field, elevated plus-maze, black/white box test, and in a new light/dark open field test, RLA/Verh rats appear to be more anxious than their RHA/Verh counterparts. Anxiety may result from their particular psychophysiological profile, i.e. increased emotionality combined with a passive coping style. In contrast, RHA/Verh rats are less responsive to stress, they show little anxiety in novel situations and tend to be impulsive and novelty (sensation) seekers. Some behavioural differences are already noticeable shortly after birth, but the full pattern appears to stabilize only after puberty. Gene-environment interactions are critical in establishing this pattern. The data reviewed indicate that the differences between RHA/Verh and RLA/Verh rats probably result from a complex interaction among divergent anxiety/emotionality characteristics, differences in locomotor activity and novelty/reward seeking, as well as active vs. passive coping styles. It is proposed further that these divergent personality types are to be found not only in other selective breeding programs but in the form of individual differences in most populations of rats used for this type of research.

Managing Science Operations During Planetary Surface: The 2010 Desert RATS Test

NASA Technical Reports Server (NTRS)

Eppler, Dean B.; Ming, D. W.

2011-01-01

Desert Research and Technology Studies (Desert RATS) is a multi-year series of hardware and operations tests carried out annually in the high desert of Arizona on the San Francisco Volcanic Field. Conducted since 1997, these activities are designed to exercise planetary surface hardware and operations in conditions where long-distance, multi-day roving is achievable. Such activities not only test vehicle subsystems through extended rough-terrain driving, they also stress communications and operations systems and allow testing of science operations approaches to advance human and robotic surface capabilities. Desert RATS is a venue where new ideas can be tested, both individually and as part of an operation with multiple elements. By conducting operations over multiple yearly cycles, ideas that make the cut can be iterated and tested during follow-on years. This ultimately gives both the hardware and the personnel experience in the kind of multi-element integrated operations that will be necessary in future human planetary exploration.

Effects of bee products on pentylenetetrazole-induced seizures in the rat.

PubMed

Zárraga-Galindo, N; Vergara-Aragón, P; Rosales-Meléndez, S; Ibarra-Guerrero, P; Domínguez-Marrufo, L E; Oviedo-García, R E; Hernández-Ramírez, H; Hernández-Téllez, B; López-Martínez, I E; Sánchez-Cervantes, I; Vázquez-García, M; Santiago, J

2011-01-01

Bee products (BP) have been used for centuries as a diet complement with claimed curative properties. The aim of this study was to determine whether oral administration of BP prevented behavioral, histological, and biochemical alterations, caused by pentylenetetrazole (PTZ)-induced kindling in rats. Male Wistar rats were employed to evaluate seizure latency, number and duration, performance in the open field test, histological alterations and mortality following BP administration. Oral administration of BP at two doses, 30 and 60 mg/kg/day, significantly lengthened latency of both clonic and tonic PTZ-induced seizures, decreased the duration and frequency of seizures and reduced mortality. In the Open Field test, BP treated groups showed increases in the number of crossed squares and rearing counts, and on optimal dose, decreases in fecal boli. Histological analysis showed in PTZ (50 and 80 mg/kg) kindling rats, lungs with inflammatory peribronchiolar, and perialveolar infiltrates. In the liver, mild losses of trabeculae, multi-vesiculated hepatocytes (steatosis) and inflammatory infiltrates in hepatic parenchyma were observed. Interestingly, in the heart, fibers were markedly separated. In testis, stratified epithelium of seminal tubules lost its normal structure, tubules had epithelium loss, spermatids were absent, and spermatogonia and Leydig cells diminished. In PTZ kindling rats treated with BP, the lungs had no inflammatory infiltrates, although the heart showed some inflammatory infiltrates. Remaining structures had normal characteristics. These results, suggest that BP can protect rats from effects of PTZ-induced kindling.

Effects of acute caffeine on anxiety-related behavior in rats chronically exposed to the drug, with some evidence of possible withdrawal-reversal.

PubMed

Hughes, Robert N; Hancock, Nicola J

2017-03-15

For 20days male and female PVG/c hooded rats were provided with caffeinated (approximately 50mg/kg/day) or unadulterated drinking water, and then their anxiety-related behavior was observed in an open field and elevated plus maze. Their choices of a brightness change were also observed in a Y maze to assess any caffeine effects on spatial memory. 24h later, all rats were tested again following an intraperitoneal injection of 50mg/kg acute caffeine, or vehicle. Earlier chronic caffeine decreased ambulation, walking, rearing, center occupancy and increased immobility in the open field thereby suggesting increased anxiety. However, occupancy of the plus-maze open arms and the Y-maze novel arm were increased by caffeine for male rats, but decreased for females probably because of sex differences in control levels of the response rather than to drug effects on anxiety and memory respectively. Following caffeine withdrawal, acute caffeine had the opposite effect to chronic treatment namely, increased open-field ambulation, walking, center occupancy and decreased immobility and defecation for caffeine-naïve rats that were suggestive of decreased anxiety. Similar but more consistent effects (plus decreased emergence latencies from a darkened start box into the open field) also typified the caffeine-experienced rats which in this case may have been accentuated by caffeine withdrawal-reversal. There was no evidence of either chronic or acute caffeine affecting spatial memory measured in the Y maze. There were also examples of lower overall activity and higher anxiety in male rats, than in females, and some sex-dependent caffeine effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of montelukast in experimental model of Parkinson's disease.

PubMed

Nagarajan, Vetrivel Babu; Marathe, Padmaja Anil

2018-06-06

Despite the availability of many drugs offering symptomatic relief in Parkinson's disease, there are no drugs available offering neuroprotective effect. Hence, it was decided to evaluate the neuroprotective effect of montelukast, an anti-inflammatory drug, in rotenone induced model of Parkinson's disease in rats. Forty eight male wistar rats were randomly divided into three groups. Group 1: Vehicle control, Group 2: Montelukast 5 mg/kg, Group 3: Montelukast 10 mg/kg. All the groups received rotenone 2.5 mg/kg intraperitoneally for 10 days as a disease inducing agent. The study drug montelukast was administered to respective groups orally from day 11 to day 24. On day 25, 24 h after 14 days of study drug administration, the rats were subjected to open field test, rota rod test and catalepsy test. Brain samples of rats from each group were collected for Malondialdehyde(MDA), Glutathione(GSH) and TNFα analysis. In the open field test both the doses of montelukast showed significant increase in the locomotor activity and also decreased the immobility time compared to vehicle (p < 0.05). In rotarod test, montelukast 5 mg/kg and 10 mg/kg showed significant increase in the time to fall, compared to vehicle (p < 0.05). In catalepsy test, both doses of montelukast significantly decreased the retraction time compared to vehicle(p < 0.05). The brain MDA levels were decreased and GSH levels were found to be higher in the two montelukast groups compared to vehicle (p < 0.05). TNFα levels too were decreased significantly on montelukast administration. Montelukast showed potential neuroprotective effect by virtue of its anti-oxidant and anti-inflammatory actions. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of 100-μT extremely low frequency electromagnetic fields exposure on hematograms and blood chemistry in rats

PubMed Central

Lai, Jinsheng; Zhang, Yemao; Zhang, Jiangong; Liu, Xingfa; Ruan, Guoran; Chaugai, Sandip; Tang, Jiarong; Wang, Hong; Chen, Chen; Wang, Dao Wen

2016-01-01

The aim of this study was to test whether extremely low frequency electromagnetic fields (ELF EMFs) affect health or not. Here, we constructed a 100-μT/50 Hz electromagnetic field atmosphere. A total of 128 rats were randomly assigned into two groups: the ELF EMF group and the sham group. The ELF EMF group was exposed to 100-μT/50-Hz ELF EMF for 20 h per day for three months; at the same time the other group was exposed to a sham device without ELF EMF. During the three months, the weight was recorded every 2 weeks, and the water intake and food intake of the animals were recorded weekly. The hematologic parameters were detected before and after the exposure, whereas blood chemistry analysis was performed every 4 weeks. The general condition of the exposed rats was not affected by ELF EMF. Compared with the sham group, the hematograms were not significantly altered in the ELF EMF group. Similarly, the blood chemistry (including lipid profile, blood glucose, liver function and renal function of rats) from the ELF EMF group showed no difference compared with rats from the control group during the three months exposure. The present study indicated that short-term exposure of 100-μT/50-Hz ELF EMF may not affect hematograms and blood chemistry in rats. PMID:26404558

The novel substituted acylproline-containing dipeptide, GVS-111, promotes the restoration of learning and memory impaired by bilateral frontal lobectomy in rats.

PubMed

Ostrovskaya, R U; Romanova, G A; Trofimov, S S; Gudasheva, T A; Voronina, T A; Halikas, J A; Seredenin, S B

1997-06-01

The present study investigated the potential benefit of the ethyl ester of N-phenylacetylprolylglycine (GVS-111) on the model of bilateral frontal lobectomy (BFL) in rats. The animals in Experiment 1 were trained in an active avoidance task and subsequently underwent BFL. The animals in Experiment 2 were first assessed in an open field and in a passive avoidance test before the BFL was performed. BFL dramatically decreased performance in the active avoidance test, disturbed habituation of horizontal activity in the open field and diminished the latency to enter the dark compartment in the passive avoidance test. GVS-111, administered in a dose of 0.5 mg/kg/day i.p. for 9 days following the operation, was found to improve performance in both active avoidance and passive avoidance and restored habituation of horizontal activity in the lobectomized animals.

The effects of repeated administration of diazepam, MK-801 and CGP 37849 on rat behavior in two models of anxiety.

PubMed

Jessa, M; Nazar, M; Bidzinski, A; Plaznik, A

1996-03-01

The effects of repeated administration of diazepam, MK-801 and CGP 37849 on rat behavior in the Vogel conflict test, and in the open field test of neophobia, were studied in rats. The drugs were given at doses active acutely, for 5 days, the last dose was administered 30 or 60 min prior to testing. It appeared that diazepam and MK-801 treated animals showed clear-cut signs of behavioral tolerance and motor sensitization, respectively. CGP 37849 was characterized by the best pharmacological profile, in that on repeated administration the drug not only retained its anxiolytic-like potency in the Vogel test, but even enhanced rat exploratory behavior in a new environment, independently of changes in animal motor activity. Repeated injections of the examined agents did not cause any significant modifications in monoamine levels and their turnover rates, in the striatum and limbic forebrain. It is concluded that the new class of competitive NMDA receptor antagonists, exemplified by CGP 37849, is the most promising candidate for clinical trials in anxiety disorders.

Periadolescent ethanol vapor exposure persistently reduces measures of hippocampal neurogenesis that are associated with behavioral outcomes in adulthood.

PubMed

Ehlers, C L; Liu, W; Wills, D N; Crews, F T

2013-08-06

Excessive alcohol consumption is prevalent among adolescents and may result in lasting neurobehavioral consequences. The use of animal models to study adolescent alcohol exposure has the advantage of allowing for the control necessary in order to evaluate the effects of ethanol on the brain and separate such effects from genetic background and other environmental insults. In the present study the effects of moderate ethanol vapor exposure, during adolescence, on measures of neurogenesis and behavioral measures were evaluated at two different times following ethanol withdrawal, in adulthood. The two groups of Wistar rats were both exposed to intermittent ethanol vapor (14 h on/10h off/day) for 35-36 days from PD 23 to PD 58 (average blood ethanol concentration: 163 mg%). In the first group, after rats were withdrawn from vapor they were subsequently assessed for locomotor activity, conflict behavior in the open field, and behaviors in the forced swim test (FST) and then sacrificed at 72 days of age. The second group of rats were withdrawn from vapor and injected for 5 days with Bromo-deoxy-Uridine (BrdU). Over the next 8 weeks they were also assessed for locomotor activity, conflict behavior in the open field, and behaviors in the FST and then sacrificed at 113/114 days of age. All rats were perfused for histochemical analyses. Ethanol vapor-exposed rats displayed hypoactivity in tests of locomotion and less anxiety-like and/or more "disinhibitory" behavior in the open field conflict. Quantitative analyses of immunoreactivity revealed a significant reduction in measures of neurogenesis, progenitor proliferation, as indexed by doublecortin (DCX), Ki67, and increased markers of cell death as indexed by cleaved caspase-3, and Fluoro-Jade at 72 days, and decreases in DCX, and increases in cleaved caspase-3 at 114 days in the ethanol vapor-exposed rats. Progenitor survival, as assessed by BrdU+, was reduced in the vapor-exposed animals that were sacrificed at 114 days. The reduction seen in DCX labeled in cell counts was significantly correlated with hypoactivity at 24h after withdrawal as well as less anxiety-like and/or more "disinhibitory" behavior in the open field conflict test at 2 and 8 weeks following termination of vapor exposure. These studies demonstrate that behavioral measures of disinhibitory behavior correlated with decreases in neurogenesis are all significantly and persistently impacted by periadolescent ethanol exposure and withdrawal in Wistar rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Preliminary evidence that abscisic acid improves spatial memory in rats.

PubMed

Qi, Cong-Cong; Ge, Jin-Fang; Zhou, Jiang-Ning

2015-02-01

Abscisic acid (ABA) is a crucial phytohormone that exists in a wide range of animals, including humans, and has multiple bioactivities. As direct derivatives of carotenoids, ABA and retinoic acid (RA) share similar molecular structures, and RA has been reported to improve spatial memory in rodents. To explore the potential effects of ABA on spatial learning and memory in rodents, 20mg/kg ABA was administered to young rats for 6weeks, and its effects on behaviour performance were evaluated through a series of behavioural tests. ABA pharmacokinetic analysis revealed that the exogenous ABA was distributed widely in the rat brain, characterised by rapid absorption and slow elimination. The behavioural tests showed that ABA increased both the duration spent in the target quadrant and the frequency it was entered in the probe test of the Morris water maze (MWM) and decreased the latency to locate the target quadrant. Moreover, ABA decreased the latency to enter the novel arm in the Y-maze test, accompanied by increases in the total entries and distance travelled in the three arms. However, there were no significant differences between the ABA-treated and control rats in the open field test and elevated plus-maze test. These results preliminarily indicate that ABA improves spatial memory in MWM and exploratory activity in Y-maze in young rats. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of pico-tesla electromagnetic field treatment on wound healing in rats.

PubMed

Trostel, C Todd; McLaughlin, Ron M; Lamberth, John G; Cooper, Robert C; Elder, Steven H; Pool, Roy R; Gao, Cheng; Cromiak, Joseph A; Boyle, Carolyn R

2003-07-01

To evaluate the effects of a pico-tesla electromagnetic field (PTEF) on healing of sutured and open skin wounds and clinicopathologic variables in rats. 64 male Fischer-344 rats. An incision made in the dorsal aspect of the neck was sutured (n = 32) or left open to heal (32). In each group, 16 rats were not PTEF-treated (controls). Wound treatment consisted of exposure to a PTEF once daily. Rats in each group were euthanatized at days 2, 4, 7, and 14. Wounds were evaluated via tensiometry (sutured wounds), digital planimetry (open wounds), laser Doppler perfusion imaging, bacteriologic culture, and histologic examination. Blood samples were collected from all rats for analysis. At day 14, sutured wounds in PTEF-treated rats were stronger (ultimate stress) and tougher (strain energy) than were sutured wounds in control rats. Open wounds in PTEF-treated rats contracted more quickly at days 2 and 4 than did those in control rats. Compared with control wounds, histologic changes (indicative of improved healing) in sutured and open wounds in PTEF-treated rats were detected as early as day 4. Laser Doppler perfusion measurements, results of CBCs, serum biochemical analyses, and bacteriologic cultures were not different between groups. Exposure to the PTEF caused no adverse effects on clinicopathologic, histologic, or bacteriologic variables tested in this study. It appears that PTEF is a safe form of adjuvant treatment for wounds and improves strength of sutured wounds and speeds contraction of open wounds.

Acute administration of fluoxetine normalizes rapid eye movement sleep abnormality, but not depressive behaviors in olfactory bulbectomized rats.

PubMed

Wang, Yi-Qun; Tu, Zhi-Cai; Xu, Xing-Yuan; Li, Rui; Qu, Wei-Min; Urade, Yoshihiro; Huang, Zhi-Li

2012-01-01

In humans, depression is associated with altered rapid eye movement (REM) sleep. However, the exact nature of the relationship between depressive behaviors and sleep abnormalities is debated. In this study, bilateral olfactory bulbectomy (OBX) was carried out to create a model of depression in rats. The sleep-wake profiles were assayed using a cutting-edge sleep bioassay system, and depressive behaviors were evaluated by open field and forced swimming tests. The monoamine content and monoamine metabolite levels in the brain were determined by a HPLC-electrochemical detection system. OBX rats exhibited a significant increase in REM sleep, especially between 15:00 and 18:00 hours during the light period. Acute treatment with fluoxetine (10 mg/kg, i.p.) immediately abolished the OBX-induced increase in REM sleep, but hyperactivity in the open field test and the time spent immobile in the forced swimming test remained unchanged. Neurochemistry studies revealed that acute administration of fluoxetine increased serotonin (5-HT) levels in the hippocampus, thalamus, and midbrain and decreased levels of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA). The ratio of 5-HIAA to 5-HT decreased in almost all regions of the brain. These results indicate that acute administration of fluoxetine can reduce the increase in REM sleep but does not change the depressive behaviors in OBX rats, suggesting that there was no causality between REM sleep abnormalities and depressive behaviors in OBX rats. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Behavioral effects of antiepileptic drugs in rats: Are the effects on mood and behavior detectable in open-field test?

PubMed

Zimcikova, Eva; Simko, Julius; Karesova, Iva; Kremlacek, Jan; Malakova, Jana

2017-11-01

Behavioral side effects of antiepileptic drugs (AEDs) are common including both positive and negative effects on mood, anxiety, depression, and psychosis. We aimed to evaluate behavioral patterns in rats after administration of lamotrigine, levetiracetam, phenytoin, topiramate, carbamazepine, gabapentin, pregabalin, and zonisamide. The open-field test was performed and locomotion, rearing, grooming, central latency and defecation were recorded over a 5min interval for each rat (8 rats in each group receiving AED and 16 controls). Kruskal-Wallis nonparametric test or ANOVA were used to assess differences among the groups. The experimental groups did not differ in latency to enter the center compartment, neither in the decline of locomotor activity in the 1st and the 5th minute of the observation, nor in number of rears. Significant differences among groups were observed in the total number of lines crossed, grooming, as well in the number of fecal pellets. Locomotor activity was significantly increased in lamotrigine, if compared with gabapentin and pregabalin (ANOVA; p <0.05). Rats exposed to topiramate displayed a significantly increased number of grooming (when compared to pregabalin: p<0.01). Defecation (the number of fecal pellets) significantly increased in the gabapentin and carbamazepine group. There are significant differences between AEDs in terms of their behavioral profile. It is of great importance to evaluate these effects in clinical practice to bring more clear insight into these positive or negative side effects of AEDs. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Wistar-Kyoto rats as an animal model of anxiety vulnerability: support for a hypervigilance hypothesis.

PubMed

McAuley, J D; Stewart, A L; Webber, E S; Cromwell, H C; Servatius, R J; Pang, K C H

2009-12-01

Inbred Wistar-Kyoto (WKY) rats have been proposed as a model of anxiety vulnerability as they display behavioral inhibition and a constellation of learning and reactivity abnormalities relative to outbred Sprague-Dawley (SD) rats. Together, the behaviors of the WKY rat suggest a hypervigilant state that may contribute to its anxiety vulnerability. To test this hypothesis, open-field behavior, acoustic startle, pre-pulse inhibition and timing behavior were assessed in WKY and Sprague-Dawley (SD) rats. Timing behavior was evaluated using a modified version of the peak-interval timing procedure. Training and testing of timing first occurred without audio-visual (AV) interference. Following this initial test, AV interference was included on some trials. Overall, WKY rats took much longer to leave the center of the arena, made fewer line crossings, and reared less, than did SD rats. WKY rats showed much greater startle responses to acoustic stimuli and significantly greater pre-pulse inhibition than did the SD rats. During timing conditions without AV interference, timing accuracy for both strains was similar; peak times for WKY and SD rats were not different. During interference conditions, however, the timing behavior of the two strains was very different. Whereas peak times for SD rats were similar between non-interference and interference conditions, peak times for WKY rats were shorter and response rates higher in interference conditions than in non-interference conditions. The enhanced acoustic startle response, greater prepulse inhibition and altered timing behavior with audio-visual interference supports a characterization of WKY strain as hypervigilant and provides further evidence for the use of the WKY strain as a model of anxiety vulnerability.

Wartime rat control, rodent ecology, and the rise and fall of chemical rodenticides.

PubMed

Keiner, Christine

2005-09-01

The story of how World War II stimulated the development of DDT, and the ensuing postwar dependence on such chemical insecticides, is well known. However, less recognition has been given to the wartime efforts to synthesize new rodenticides to fight rat-borne epidemics. Baltimore, Maryland served as the site for field tests of the powerful new compound alpha naphthyl thiourea (ANTU) from 1942-1946. This experimental campaign sparked debates over the efficacy of controlling rats via chemical warfare instead of environmental sanitation, which led to the ironic conclusion that urban rat control demanded an ecological, rather than technological, approach.

ACTION OF 50 HZ MAGNETIC FIELDS ON NEURITE OUTGROWTH IN PHEOCHROMOCYTOMA CELLS

EPA Science Inventory

This study tests the capacity of 50-Hz magnetic and electric fields to stimulate neurite outgrowth in PC-12D cells, a cell line which originated from a pheochromocytoma in rat adrenal medulla. he cells were plated on collagen-coated plastic petri dishes and exposed to sinusoidal ...

Anxiolytic effects of environmental enrichment attenuate sex-related anxiogenic effects of scopolamine in rats.

PubMed

Hughes, Robert N; Otto, Maria T

2013-01-10

In groups of four same-sexed animals, PVG/c hooded rats were housed for 4.5 months in standard or enriched cages containing several objects that could be explored and manipulated. On separate occasions, each rat then experienced two consecutive daily trials in an open field, a light-dark box or a Y maze with arm inserts that enabled an acquisition trial comprising one black and one white arm to be changed for a retention trial consisting of two black arms. Before their trials in the open field and light-dark box, and following each acquisition trial in the Y maze, the rats received an intraperitoneal injection of 2 mg/kg scopolamine or isotonic saline. In the open field, enrichment led to higher levels of ambulation, walking, rearing and occupancy of the center of the apparatus and shorter emergence latencies from the dark into the light compartment of the light-dark box accompanied by more entries of this compartment. Enrichment also increased entries of and time spent in the changed (or novel) Y-maze arm only for male rats treated with scopolamine. The drug decreased rearing and increased grooming in the open field as well as increasing emergence latencies and decreasing entries of and the time spent on the light compartment of the light-dark box. The main results were interpreted as enrichment having attenuated anxiogenic effects of the behavioral testing and the action of scopolamine for male (but not female) rats in their choices of the novel arm in the Y maze. Copyright © 2012 Elsevier Inc. All rights reserved.

[Behavior and functional state of the dopaminergic brain system in pups of depressive WAG/Rij rats].

PubMed

Malyshev, A V; Razumkina, E V; Rogozinskaia, É Ia; Sarkisova, K Iu; Dybynin, V A

2014-01-01

In the present work, it has been studied for the first time behavior and functional state of the dopaminergic brain system in pups of "depressive" WAG/Rij rats. Offspring of "depressive" WAG/Rij rats at age of 6-16 days compared with offspring of "normal" (non-depressed) outbred rats of the same age exhibited reduced rate of pshychomotor development, lower body weight, attenuation in integration of coordinated reflexes and vestibular function (greater latency of righting reflex, abnormal negative geotaxis), hyper-reactivity to tactile stimulation, reduced motivation to contact with mother (reduced infant-mother attachment). Differences in a nest seeking response induced by olfactory stimuli (olfactory discrimination test) and in locomotor activity (tests "gait reflex" and "small open field") have not been revealed. Acute injection of the antagonist of D2-like dopamine receptors clebopride 20 min before testing aggravated mother-oriented behavior in 15-days-old pups of both "depressive" and "non-depressive" rats. However this effect was greater in pups of "depressive" WAG/Rij rats compared with pups of "normal" rats that may indicate reduced functional activity of the dopaminergic brain system in offspring of "depressive" rats. It is proposed that reduced attachment behavior in pups of "depressive" WAG/Rij rats might be a consequence of maternal depression and associated with it reduced maternal care. Moreover, reduced attachment behavior in pups of "depressive" rats might be an early precursor (a marker) of depressive-like pathology which become apparent later in life (approximately at age of 3 months).

Defective balancing ability and hyperactivity in the CLX (circling behavior linked to the X-chromosome) mutant rat.

PubMed

Fuji, Jun-ichiro; Tanabe, Hiroyuki; Fukuda, Ryo; Ooshima, Yojiro

2003-12-01

We have reported that the recently described circling behavior rat (CLX) is a hereditary mutant controlled by a single sex-linked recessive gene (gene symbol: clx). This mutant shows intermittent circle walking and/or running and head tossing with the neck twisted. The abnormal behavior begins to appear around weaning and continues throughout life. In the present study, behavioral tests were performed during the suckling and post-weaning periods and when the rats reached maturity, and the following peculiar abnormalities were revealed: (1) in the righting reflex test, the CLX young show a tendency to take a longer time to revert to normal posture; (2) in the negative geotaxis test, they had difficulty moving upward at 12 days of age; (3) in the air righting reflex test, they frequently fell on their backs or shoulders even after weaning; (4) almost none of the CLX rats showed nystagmus, which is invariably observed in normal rats after rotating stimulation, at 20 weeks of age; and (5) they showed hyperactivity in the open field test at the age of 5 or 6 weeks and a higher degree of locomotor activity in the home cage at the age of 7 and 15 weeks. These results suggest that CLX mutant rats may have some defect in vestibular function (balance sense) or abnormalities in an area of the central nervous system responsible for posture control, e.g., in the dopaminergic or GABAergic neurons.

Acute neuroprotective effects of extremely low-frequency electromagnetic fields after traumatic brain injury in rats.

PubMed

Yang, Yang; Li, Ling; Wang, Yan-Gang; Fei, Zhou; Zhong, Jun; Wei, Li-Zhou; Long, Qian-Fa; Liu, Wei-Ping

2012-05-10

Traumatic brain injury commonly has a result of a short window of opportunity between the period of initial brain injury and secondary brain injury, which provides protective strategies and can reduce damages of brain due to secondary brain injury. Previous studies have reported neuroprotective effects of extremely low-frequency electromagnetic fields. However, the effects of extremely low-frequency electromagnetic fields on neural damage after traumatic brain injury have not been reported yet. The present study aims to investigate effects of extremely low-frequency electromagnetic fields on neuroprotection after traumatic brain injury. Male Sprague-Dawley rats were used for the model of lateral fluid percussion injury, which were placed in non-electromagnetic fields and 15 Hz (Hertz) electromagnetic fields with intensities of 1 G (Gauss), 3 G and 5 G. At various time points (ranging from 0.5 to 30 h) after lateral fluid percussion injury, rats were treated with kainic acid (administered by intraperitoneal injection) to induce apoptosis in hippocampal cells. The results were as follows: (1) the expression of hypoxia-inducible factor-1α was dramatically decreased during the neuroprotective time window. (2) The kainic acid-induced apoptosis in the hippocampus was significantly decreased in rats exposed to electromagnetic fields. (3) Electromagnetic fields exposure shortened the escape time in water maze test. (4) Electromagnetic fields exposure accelerated the recovery of the blood-brain barrier after brain injury. These findings revealed that extremely low-frequency electromagnetic fields significantly prolong the window of opportunity for brain protection and enhance the intensity of neuroprotection after traumatic brain injury. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A ligand-based comparative molecular field analysis (CoMFA) and homology model based molecular docking studies on 3', 4'-dihydroxyflavones as rat 5-lipoxygenase inhibitors: Design of new inhibitors.

PubMed

Ahamed, T K Shameera; Muraleedharan, K

2017-12-01

In this study, ligand based comparative molecular field analysis (CoMFA) with five principal components was performed on class of 3', 4'-dihydroxyflavone derivatives for potent rat 5-LOX inhibitors. The percentage contributions in building of CoMFA model were 91.36% for steric field and 8.6% for electrostatic field. R 2 values for training and test sets were found to be 0.9320 and 0.8259, respectively. In case of LOO, LTO and LMO cross validation test, q 2 values were 0.6587, 0.6479 and 0.5547, respectively. These results indicate that the model has high statistical reliability and good predictive power. The extracted contour maps were used to identify the important regions where the modification was necessary to design a new molecule with improved activity. The study has developed a homology model for rat 5-LOX and recognized the key residues at the binding site. Docking of most active molecule to the binding site of 5-LOX confirmed the stability and rationality of CoMFA model. Based on molecular docking results and CoMFA contour plots, new inhibitors with higher activity with respect to the most active compound in data set were designed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heart Rate Variability in Nonlinear Rats with Different Orientation and Exploratory Activity in the Open Field.

PubMed

Kur'yanova, E V; Teplyi, D L; Zhukova, Yu D; Zhukovina, N V

2015-12-01

The basic behavioral activity of nonlinear rats was evaluated from the sum of crossed peripheral and central squares and peripheral and central rearing postures in the open fi eld test. This index was low (<20 episodes), intermediate (20-29 episodes), or high (>30 episodes). Male rats with high score of orientation and exploratory activity were characterized by higher indexes of total heart rate variability than rats with low or intermediate activity. Specimens with a greater contribution of VLF waves into the total power spectrum of heart rate variability were shown to dominate among the rats with high behavioral activity. Our results are consistent with the notions of a suprasegmental nature of VLF waves.

Function of the centromedial amygdala in reward devaluation and open-field activity.

PubMed

Kawasaki, K; Glueck, A C; Annicchiarico, I; Papini, M R

2015-09-10

The present research aimed at determining the role played by the amygdala in reward devaluation using transient inactivation induced by lidocaine microinfusions into the centromedial region. Two situations involving reward devaluation were tested in rats: consummatory successive negative contrast (cSNC) and anticipatory negative contrast (ANC). In cSNC, rats exposed to a downshift from 32% to 4% sucrose consume less 4% sucrose than rats always exposed to 4% sucrose. Extensive evidence suggests that reward devaluation in the cSNC situation is accompanied by negative emotion. In ANC, rats consume less 4% sucrose when each session is closely followed by access to 32% sucrose rather than by 4% sucrose. Evidence suggests that reward devaluation in the ANC situation does not involve negative emotions; rather, ANC appears to involve Pavlovian anticipation of the higher value solution. To test the effects of lidocaine microinfusions in a situation known to induce negative emotion, but unrelated to reward devaluation, animals were also exposed to a lighted open field. Centromedial amygdala inactivation reduced the cSNC effect and increased exploratory behavior in the open field, both effects consistent with a reduction in negative emotional state. However, no detectable effects of amygdala inactivation were observed in the ANC situation. These results suggest that, first, the function of the amygdala is not unique to reward devaluation and, second, it is concerned with tagging the devaluation experience with aversive valence. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

NASA Desert RATS 2011 Education Pilot Project and Classroom Activities

NASA Technical Reports Server (NTRS)

Gruener, J. E.; McGlone, M.; Allen, J.; Tobola, K.; Graff, P.

2012-01-01

The National Aeronautics and Space Administration's (NASA's) Desert Research and Technology Studies (Desert RATS) is a multi-year series of tests of hardware and operations carried out annually in the high desert of Arizona, as an analog to future exploration activities beyond low Earth orbit [1]. For the past several years, these tests have occurred in the San Francisco Volcanic Field, north of Flagstaff. For the 2011 Desert RATS season, the Exploration Systems Mission Directorate (ESMD) at NASA headquarters provided support to develop an education pilot project that would include student activities to parallel the Desert RATS mission planning and exploration activities in the classroom, and educator training sessions. The development of the pilot project was a joint effort between the NASA Johnson Space Center (JSC) Astromaterials Research and Exploration Science (ARES) Directorate and the Aerospace Education Services Project (AESP), managed at Penn State University.

Learned helplessness and social avoidance in the Wistar-Kyoto rat

PubMed Central

Nam, Hyungwoo; Clinton, Sarah M.; Jackson, Nateka L.; Kerman, Ilan A.

2014-01-01

The Wistar-Kyoto (WKY) rat is an established depression model characterized by elevated anxiety- and depression-like behavior across a variety of tests. Here we further characterized specific behavioral and functional domains relevant to depression that are altered in WKY rats. Moreover, since early-life experience potently shapes emotional behavior, we also determined whether aspects of WKYs' phenotype were modifiable by early-life factors using neonatal handling or maternal separation. We first compared WKYs' behavior to that of Sprague–Dawley (SD), Wistar, and Spontaneously Hypertensive (SHR) rats in: the open field test, elevated plus maze, novelty-suppressed feeding test, a social interaction test, and the forced swim test (FST). WKYs exhibited high baseline immobility in the FST and were the only strain to show increased immobility on FST Day 2 vs. Day 1 (an indicator of learned helplessness). WKYs also showed greater social avoidance, along with enlarged adrenal glands and hearts relative to other strains. We next tested whether neonatal handling or early-life maternal separation stress influenced WKYs' behavior. Neither manipulation affected their anxiety- and depressive-like behaviors, likely due to a strong genetic underpinning of their phenotype. Our findings indicate that WKY rats are a useful model that captures specific functional domains relevant to clinical depression including: psychomotor retardation, behavioral inhibition, learned helplessness, social withdrawal, and physiological dysfunction. WKY rats appear to be resistant to early-life manipulations (i.e., neonatal handling) that are therapeutic in other strains, and may be a useful model for the development of personalized anti-depressant therapies for treatment resistant depression. PMID:24744709

Learned helplessness and social avoidance in the Wistar-Kyoto rat.

PubMed

Nam, Hyungwoo; Clinton, Sarah M; Jackson, Nateka L; Kerman, Ilan A

2014-01-01

The Wistar-Kyoto (WKY) rat is an established depression model characterized by elevated anxiety- and depression-like behavior across a variety of tests. Here we further characterized specific behavioral and functional domains relevant to depression that are altered in WKY rats. Moreover, since early-life experience potently shapes emotional behavior, we also determined whether aspects of WKYs' phenotype were modifiable by early-life factors using neonatal handling or maternal separation. We first compared WKYs' behavior to that of Sprague-Dawley (SD), Wistar, and Spontaneously Hypertensive (SHR) rats in: the open field test, elevated plus maze, novelty-suppressed feeding test, a social interaction test, and the forced swim test (FST). WKYs exhibited high baseline immobility in the FST and were the only strain to show increased immobility on FST Day 2 vs. Day 1 (an indicator of learned helplessness). WKYs also showed greater social avoidance, along with enlarged adrenal glands and hearts relative to other strains. We next tested whether neonatal handling or early-life maternal separation stress influenced WKYs' behavior. Neither manipulation affected their anxiety- and depressive-like behaviors, likely due to a strong genetic underpinning of their phenotype. Our findings indicate that WKY rats are a useful model that captures specific functional domains relevant to clinical depression including: psychomotor retardation, behavioral inhibition, learned helplessness, social withdrawal, and physiological dysfunction. WKY rats appear to be resistant to early-life manipulations (i.e., neonatal handling) that are therapeutic in other strains, and may be a useful model for the development of personalized anti-depressant therapies for treatment resistant depression.

Effects of heat stress on endocrine functions & behaviour in the pre-pubertal rat.

PubMed

Mete, Fatih; Kilic, Ertugrul; Somay, Adnan; Yilmaz, Bayram

2012-01-01

Heat stress related hyperthermia may cause damage to various organ systems. There are very few studies on the effects of hyperthermia on the endocrine system. We therefore, investigated effects of exogenously induced hyperthermia on adrenal, testicular and thyroid functions and behavioural alterations in pre-pubertal male Sprague-Dawley rats. Three groups of 30-day old rats (n=7 per group) were used. Body temperature was increased to 39 °C (Group I) and 41 °C (Group II) in a hyperthermia induction chamber for 30 min. The rats in the Group III served as control (36 °C). All animals received saline and were decapitated 48 h after the experiments. Serum free triiodothyronin (fT3), free thyroxine (fT4), total testosterone and dehydroepiandrosterone sulphate (DHEA-S) levels were determined by chemiluminescence assay, and corticosterone by enzyme immunoassay. Testes, pituitary and adrenal glands were dissected out and processed for histopathological examination. To assess activity and anxiety of the animals, the open field test and elevated-0-maze test, respectively, were used in all groups 24 h before (day 29) and after (day 31) hyperthermia induction. Serum corticosterone levels (3.22 ± 1.3) were significantly reduced in the 39 °C (1.3 ± 0.9) and 41 °C (1.09 ± 0.7) hyperthermia groups (P<0.01) compared to controls. Serum levels of thyroid hormones did not significantly differ among the groups. DHEA-S and testosterone values were below the limit of detection in all groups. Histopathological examination revealed that there was mild hydropic degeneration in the pituitary and adrenal glands. Apoptotic germ cells were seen in the seminiferous tubules of pre-pubertal male rats exposed to hyperthermia (41 °C). Progression time in the open field test was significantly decreased and anxiety test scores increased in animals exposed to 39 °C compared to the control group (P<0.01). These parameters were more pronounced in the 41 °C hyperthermia group. Our results show that heat exposure-induced stress may cause delayed reduction in serum corticosterone levels which may be associated with behavioural deficits in pre-pubertal male rats.

Degraded speech sound processing in a rat model of fragile X syndrome

PubMed Central

Engineer, Crystal T.; Centanni, Tracy M.; Im, Kwok W.; Rahebi, Kimiya C.; Buell, Elizabeth P.; Kilgard, Michael P.

2014-01-01

Fragile X syndrome is the most common inherited form of intellectual disability and the leading genetic cause of autism. Impaired phonological processing in fragile X syndrome interferes with the development of language skills. Although auditory cortex responses are known to be abnormal in fragile X syndrome, it is not clear how these differences impact speech sound processing. This study provides the first evidence that the cortical representation of speech sounds is impaired in Fmr1 knockout rats, despite normal speech discrimination behavior. Evoked potentials and spiking activity in response to speech sounds, noise burst trains, and tones were significantly degraded in primary auditory cortex, anterior auditory field and the ventral auditory field. Neurometric analysis of speech evoked activity using a pattern classifier confirmed that activity in these fields contains significantly less information about speech sound identity in Fmr1 knockout rats compared to control rats. Responses were normal in the posterior auditory field, which is associated with sound localization. The greatest impairment was observed in the ventral auditory field, which is related to emotional regulation. Dysfunction in the ventral auditory field may contribute to poor emotional regulation in fragile X syndrome and may help explain the observation that later auditory evoked responses are more disturbed in fragile X syndrome compared to earlier responses. Rodent models of fragile X syndrome are likely to prove useful for understanding the biological basis of fragile X syndrome and for testing candidate therapies. PMID:24713347

Adolescent chronic restraint stress (aCRS) elicits robust depressive-like behavior in freely cycling, adult female rats without increasing anxiety-like behaviors.

PubMed

Hibicke, Meghan; Graham, Martha A; Hayslett, Renée L

2017-04-01

Stress during times of rapid development is a risk factor for Major Depressive Disorder, a mood disorder that disproportionately affects women. We developed an adolescent chronic restraint stress (aCRS) protocol using female rats to address the impact of adolescent stress on female adult depressive-like behavior. Animals were divided into 4 treatment groups: not restrained:saline (NRSAL), not restrained:desipramine (NRDES), restrained:saline (RSAL), and restrained:desipramine (RDES). NRSAL and NRDES rats were housed in a separate colony room from RSAL and RDES rats. All animals were weighed and handled daily. Beginning postnatal day (PND) 34(±1), RSAL and RDES rats were restrained for 1 hour daily for 14 consecutive days. Beginning PND 55(±1), NRDES and RDES rats were given subcutaneous desipramine (5 mg/kg), which served as a positive control, daily for 14 consecutive days. During that same time period, NRSAL and RSAL rats were given subcutaneous saline daily. aCRS (RSAL and RDES) rats showed significantly attenuated weight gain compared with nonrestrained (NRSAL and NRDES) rats during the restraint period. Weight gain normalized after the final restraint session. Behavioral testing took place PND 68-69(±1), and included open field testing, the elevated plus maze, locomotor activity, and the forced swim test (FST). RSAL rats showed significantly more immobility in the FST versus all other groups, indicating depressive-like behavior. No differences between groups were observed in the other behavioral measures. These results indicate that aCRS elicits depressive-like behavioral characteristics in adult female rats without increasing anxiety-like behaviors. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Normative data for Chinese compound remote associate problems.

PubMed

Wu, Ching-Lin; Chen, Hsueh-Chih

2017-12-01

The Remote Associates Test (RAT) is a well-known measure of creativity, with each item on the RAT is composed of three unrelated stimulus words. The participant's task is to find an answer in the form of a word that could combine with each of the stimulus words, thus forming three new actual nouns. Researchers have modified the RAT to develop compound remote associate problems that emphasize combining vocabulary to form compound words. In the field of creativity research for Mandarin speakers, the Chinese RAT has been widely applied for over 10 years. The original RAT, compound remote associate problems, and Chinese RAT have various common advantages, such as being convenient to use and having objective scoring; additionally, the development of items for certain tests is easy and satisfies the requirements of psychological assessments in terms of the quantity of items. Currently, many language editions of the RAT and compound remote associate problems already exist. In particular, the English and Italian versions of these tests already have derived normative data. Because approximately 20% of the world's population are native Mandarin speakers, and because increasing numbers of people are choosing Mandarin as a second language, the need to increase Mandarin-language resources is growing; however, normative data for the Chinese RAT still do not exist. To address this issue, in the present study we developed Chinese compound remote associate problems and analyzed the passing rates by items, problem solving times, and various normative data, using the responses of 253 subjects in three experiments.

Effects of Chronic Vitamin D3 Hormone Administration on Anxiety-Like Behavior in Adult Female Rats after Long-Term Ovariectomy

PubMed Central

Fedotova, Julia; Pivina, Svetlana; Sushko, Anastasia

2017-01-01

The present preclinical study was created to determine the therapeutic effects of vitamin D hormone treatment as an adjunctive therapy alone or in a combination with low dose of 17β-estradiol (17β-E2) on anxiety-like behavior in female rats with long-term absence of estrogen. Accordingly, the aim of the current study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg subcutaneously, SC, once daily, for 14 days) on the anxiety-like state after long-term ovariectomy in female rats. Twelve weeks postovariectomy, cholecalciferol was administered to ovariectomized (OVX) rats and OVX rats treated with 17β-E2 (0.5 µg/rat SC, once daily, for 14 days). Anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light/dark test (LDT), and locomotor and grooming activities were tested in the open field test (OFT). Cholecalciferol at two doses of 1.0 and 2.5 mg/kg alone or in combination with 17β-E2 produced anxiolytic-like effects in OVX rats as evidenced in the EPM and the LDT, as well as increased grooming activity in the OFT. Our results indicate that cholecalciferol, at two doses of 1.0 and 2.5 mg/kg, has a profound anxiolytic-like effects in the experimental rat model of long-term estrogen deficiency. PMID:28054941

Spatial encoding in spinal sensorimotor circuits differs in different wild type mice strains

PubMed Central

Thelin, Jonas; Schouenborg, Jens

2008-01-01

Background Previous studies in the rat have shown that the spatial organisation of the receptive fields of nociceptive withdrawal reflex (NWR) system are functionally adapted through experience dependent mechanisms, termed somatosensory imprinting, during postnatal development. Here we wanted to clarify 1) if mice exhibit a similar spatial encoding of sensory input to NWR as previously found in the rat and 2) if mice strains with a poor learning capacity in various behavioural tests, associated with deficient long term potention, also exhibit poor adaptation of NWR. The organisation of the NWR system in two adult wild type mouse strains with normal long term potentiation (LTP) in hippocampus and two adult wild type mouse strains exhibiting deficiencies in corresponding LTP were used and compared to previous results in the rat. Receptive fields of reflexes in single hindlimb muscles were mapped with CO2 laser heat pulses. Results While the spatial organisation of the nociceptive receptive fields in mice with normal LTP were very similar to those in rats, the LTP impaired strains exhibited receptive fields of NWRs with aberrant sensitivity distributions. However, no difference was found in NWR thresholds or onset C-fibre latencies suggesting that the mechanisms determining general reflex sensitivity and somatosensory imprinting are different. Conclusion Our results thus confirm that sensory encoding in mice and rat NWR is similar, provided that mice strains with a good learning capability are studied and raise the possibility that LTP like mechanisms are involved in somatosensory imprinting. PMID:18495020

Long-term voluntary exercise prevents post-weaning social isolation-induced cognitive impairment in rats.

PubMed

Okudan, Nilsel; Belviranlı, Muaz

2017-09-30

This study aimed to determine the effect of exercise on locomotion, anxiety-related behavior, learning, and memory in socially isolated post-weaning rats, as well as the correlation between exercise and the concentration of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus. Rats were randomly assigned to three groups: the control group; the social isolation group; the social isolation plus exercise (SIE) group. Social isolation conditions, with or without exercise were maintained for 90d, and then multiple behavioral tests, including the open-field test, elevated plus maze test, and Morris water maze (MWM) test were administered. Following behavioral assessment, hippocampal tissue samples were obtained for measurement of BDNF and NGF. There wasn't a significant difference in locomotor activity between the groups (P>0.05). Anxiety scores were higher in the socially isolated group (P<0.05) than in the SIE group (P<0.05). According to the probe trial session of the MWM test results, exercise training improved platform crossings' number in the socially isolated rats (P<0.05). Exercise training ameliorated social isolation-induced reduction in hippocampal BDNF and NGF content (P<0.05). These findings suggest that exercise training improves cognitive functions via increasing hippocampal BDNF and NGF concentrations in socially isolated post-weaning rats. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Benefits of Preventive Administration of Chlorella sp. on Visceral Pain and Cystitis Induced by a Single Administration of Cyclophosphamide in Female Wistar Rat.

PubMed

Hidalgo-Lucas, Sophie; Rozan, Pascale; Guérin-Deremaux, Laetitia; Baert, Blandine; Violle, Nicolas; Saniez-Degrave, Marie-Hélène; Bisson, Jean-François

2016-05-01

Chlorella sp. is a green microalgae containing nutrients, vitamins, minerals, and chlorophyll. In some communities, Chlorella sp. is a traditional medicinal plant used for the management of inflammation-related diseases. In a rat model, ROQUETTE Chlorella sp. (RCs) benefits were investigated on visceral pain and associated inflammatory parameters related to cystitis both induced by cyclophosphamide (CYP). RCs was orally administered every day from day 1-16 (250 and 500 mg/kg body weight). Six hours after an intraperitoneal injection of 200 mg/kg body weight of CYP, body temperature, general behavior, food intake, and body weight were recorded. Twenty-four hours after CYP injection, rats were tested in two behavioral tests, an open field and the aversive light stimulus avoidance conditioning test, to evaluate the influence of pain on general activity and learning ability of rats. After euthanasia, bladders were weighed, their thickness was scored, and the urinary hemoglobin was measured. RCs orally administered at the two dosages significantly reduced visceral pain and associated inflammatory parameters related to cystitis both induced by CYP injection, and improved rat behavior. To conclude, RCs demonstrated beneficial effects against visceral pain and cystitis.

The antidepressant-like effects of topiramate alone or combined with 17β-estradiol in ovariectomized Wistar rats submitted to the forced swimming test.

PubMed

Molina-Hernández, Miguel; Téllez-Alcántara, N Patricia; Olivera-López, Jorge I; Jaramillo, M Teresa

2014-09-01

There is a significant delay in the clinical response of antidepressant drugs, and antidepressant treatments produce side effects. We examined the relationship between 17β-estradiol and topiramate in ovariectomized Wistar rats submitted to the forced swimming test (FST). Topiramate was administered alone or combined with 17β-estradiol to ovariectomized rats submitted to the FST. Topiramate (20 mg/kg, P < 0.05; 30 mg/kg, P < 0.05) reduced immobility by increasing swimming; these effects were antagonized by finasteride (50 mg/kg). In interaction experiments, topiramate (10 mg/kg) plus 17β-estradiol (5 micrograms per rat; P < 0.05) reduced immobility by increasing swimming behavior. Besides, 17β-estradiol (2.5 micrograms per rat) shortened the onset of the antidepressant-like effects of topiramate (P < 0.05). In the open field test, topiramate alone or combined with 17β-estradiol (P < 0.05) reduced locomotion. Topiramate alone or combined with 17β-estradiol produced antidepressant-like actions; and 17β-estradiol shortened the onset of the antidepressant-like effects of topiramate.

Exercise protects myelinated fibers of white matter in a rat model of depression.

PubMed

Xiao, Qian; Wang, Feifei; Luo, Yanmin; Chen, Linmu; Chao, Fenglei; Tan, Chuanxue; Gao, Yuan; Huang, Chunxia; Zhang, Lei; Liang, Xin; Tang, Jing; Qi, Yingqing; Jiang, Lin; Zhang, Yi; Zhou, Chunni; Tang, Yong

2018-02-15

The antidepressive effects of exercise have been a focus of research and are hypothesized to remodel the brain networks constructed by myelinated fibers. However, whether the antidepressant effects of exercise are dependent on changes in white matter myelination are unknown. Therefore, we chose chronic unpredictable stress (CUS) as a model of depression and designed an experiment. After a 4-week CUS period, 40 animals were tested using the sucrose preference test (SPT) and the open field test (OFT). The depressed rats then underwent 4-week running exercise. Next, electron microscopy and unbiased stereological methods were used to investigate white matter changes in the rats. After the 4-week CUS stimulation, body weight, sucrose preference and scores on the OFT were significantly lower in the depression rats than in the unstressed rats (p < .05). After undergoing a 4-week running exercise, the depression rats showed a significantly greater sucrose preference than the depression control rats without running exercise (p < .05). Furthermore, the white matter parameters of the depression rats (including the white matter volumes, the length and volumes of myelinated fibers, and the volumes and thickness of the myelin sheaths) were significantly reduced after the CUS period (p < .05). However, these white matter parameters were significantly increased after running exercise (p < .05). The present study is the first to provide evidence that running exercise has positive effects on white matter and the myelinated fibers of white matter in depressed rats, and this evidence might provide an important theoretical basis for the exercise-mediated treatment of depression. © 2017 Wiley Periodicals, Inc.

Effects of amphetamine on striatal dopamine release, open-field activity, and play in Fischer 344 and Sprague-Dawley rats.

PubMed

Siviy, Stephen M; McDowell, Lana S; Eck, Samantha R; Turano, Alexandra; Akopian, Garnik; Walsh, John P

2015-12-01

Previous work from our laboratories has shown that juvenile Fischer 344 (F344) rats are less playful than other strains and also appear to be compromised in dopamine (DA) functioning. To determine whether the dysfunctional play in this strain is associated with deficits in the handling and delivery of vesicular DA, the following experiments assessed the extent to which F344 rats are differentially sensitive to the effects of amphetamine. When exposed to amphetamine, striatal slices obtained from F344 rats showed a small increase in unstimulated DA release when compared with slices from Sprague-Dawley rats; they also showed a more rapid high K+-mediated release of DA. These data provide tentative support for the hypothesis that F344 rats have a higher concentration of cytoplasmic DA than Sprague-Dawley rats. When rats were tested for activity in an open field, F344 rats presented a pattern of results that was consistent with either an enhanced response to amphetamine (3 mg/kg) or a more rapid release of DA (10 mg/kg). Although there was some indication that amphetamine had a dose-dependent differential effect on play in the two strains, play in F344 rats was not enhanced to any degree by amphetamine. Although these results are not consistent with our working hypothesis that F344 rats are less playful because of a deficit in vesicular release of DA, they still suggest that this strain may be a useful model for better understanding the role of DA in social behavior during the juvenile period.

HDU Deep Space Habitat (DSH) Overview

NASA Technical Reports Server (NTRS)

Kennedy, Kriss J.

2011-01-01

This paper gives an overview of the National Aeronautics and Space Administration (NASA) led multi-center Habitat Demonstration Unit (HDU) project Deep Space Habitat (DSH) analog that will be field-tested during the 2011 Desert Research and Technologies Studies (D-RATS) field tests. The HDU project is a technology pull project that integrates technologies and innovations from multiple NASA centers. This project will repurpose the HDU Pressurized Excursion Module (PEM) that was field tested in the 2010 D-RATS, adding habitation functionality to the prototype unit. The 2010 configuration of the HDU-PEM consisted of a lunar surface laboratory module that was used to bring over 20 habitation-related technologies together in a single platform that could be tested as an advanced habitation analog in the context of mission architectures and surface operations. The 2011 HDU-DSH configuration will build upon the PEM work, and emphasize validity of crew operations (habitation and living, etc), EVA operations, mission operations, logistics operations, and science operations that might be required in a deep space context for Near Earth Object (NEO) exploration mission architectures. The HDU project consists of a multi-center team brought together in a skunkworks approach to quickly build and validate hardware in analog environments. The HDU project is part of the strategic plan from the Exploration Systems Mission Directorate (ESMD) Directorate Integration Office (DIO) and the Exploration Mission Systems Office (EMSO) to test destination elements in analog environments. The 2011 analog field test will include Multi Mission Space Exploration Vehicles (MMSEV) and the DSH among other demonstration elements to be brought together in a mission architecture context. This paper will describe overall objectives, various habitat configurations, strategic plan, and technology integration as it pertains to the 2011 field tests.

Neonatal exposure to fenoterol and betamethasone: effects on the behavioral development in the rat.

PubMed

Pitzer, Martina; Schmidt, Martin H

2009-01-01

We investigated longitudinally the behavioral development in the rat following exposure to beta-agonists and glucocorticoids (GC). Neonatal rats received either 1 mg/kg fenoterol (FEN), 0.3 mg/kg betamethasone (BET), or saline (SAL). Weanling and young adult rats were tested in the open field, the elevated-plus maze, and the water maze. FEN-treated as well as BET-treated animals displayed increased anxiety-like behavior. Furthermore, BET-treated adult animals showed a reduced locomotor activity. An enhanced 24-h memory in the water maze in both treatment groups may be facilitated by emotional arousal due to the increased anxiety levels. The possible neurobiological underpinnings are discussed in detail.

Failure to produce taste-aversion learning in rats exposed to static electric fields and air ions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Creim, J.A.; Lovely, R.H.; Weigel, R.J.

1995-12-01

Taste-aversion (TA) learning was measured to determine whether exposure to high-voltage direct current (HVdc) static electric fields can produce TA learning in male Long Evans rats. Fifty-six rats were randomly distributed into four groups of 14 rats each. All rats were placed on a 20 min/day drinking schedule for 12 consecutive days prior to receiving five conditioning trials. During the conditioning trials, access to 0.1% sodium saccharin-flavored water was given for 20 min, followed 30 min later by one of four treatments. Two groups of 14 rats each were individually exposed to static electric fields and air ions, one groupmore » to +75 kV/m (+2 {times} 10{sup 5} air ions/cm{sup 3}) and the other group to {minus}75 kV/m ({minus}2 {times} 10{sup 5} air ions/cm{sup 3}). Two other groups of 14 rats each served as sham-exposed controls, with the following variation in one of the sham-exposed groups: this group was subdivided into two subsets of seven rats each, so that a positive control group could be included to validate the experimental design. The positive control group (n = 7) was injected with cyclophosphamide 25 mg/kg, i.p., 30 min after access to saccharin-flavored water on conditioning days, whereas the other subset of seven rats was similarly injected with an equivalent volume of saline. Access to saccharin-flavored water on conditioning days was followed by the treatments described above and was alternated daily with water recovery sessions in which the rats received access to water for 20 min in the home cage without further treatment. Following the last water-recovery session, a 20 min, two-bottle preference test (between water and saccharin-flavored water) was administered to each group. The positive control group did show TA learning, thus validating the experimental protocol.« less

Early ethanol exposure and vinpocetine treatment alter learning- and memory-related proteins in the rat hippocampus and prefrontal cortex.

PubMed

Swart, Patricia C; Currin, Christopher B; Russell, Vivienne A; Dimatelis, Jacqueline J

2017-05-01

This study investigates the effects of early exposure to ethanol on cognitive function and neural plasticity-related proteins in the rat brain. Sprague-Dawley rats were administered 12% ethanol solution (4 g/kg/day i.p.) or saline from P4 to P9. Vinpocetine, a phosphodiesterase type 1 inhibitor, was tested to determine whether it could reverse any changes induced by early ethanol exposure. Hence, from P25 to P31, ethanol-exposed male rats were injected with vinpocetine (20 mg/kg/day i.p.) or vehicle (DMSO) prior to undergoing behavioral testing in the open field and Morris water maze (MWM) tests. Ethanol exposure did not adversely affect spatial memory in the MWM. A key finding in this study was a significant ethanol-induced change in the function of the phosphorylated extracellular signal-related kinase (P-ERK) signaling pathway in the prefrontal cortex (PFC) and dorsal hippocampus (DH) of rats that did not display overt behavioral deficits. The P-ERK/ERK ratio was decreased in the PFC and increased in the DH of ethanol-exposed rats compared with controls. Rats that received vinpocetine in addition to ethanol did not display any behavioral changes but did show alterations in neural plasticity-related proteins. Mitogen-activated protein kinase phosphatase was increased, whereas brain-derived neurotrophic factor was decreased, in the PFC of vinpocetine-treated ethanol-exposed rats, and phosphorylated-glycogen synthase kinase β and synaptophysin were increased in the DH of these rats. This study provides insight into the long-term effects of early ethanol exposure and its interaction with vinpocetine in the rat brain. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Differential effects of exposure to low-light or high-light open-field on anxiety-related behaviors; relationship to c-Fos expression in serotonergic and non-serotonergic neurons in the dorsal raphe nucleus

PubMed Central

Bouwknecht, J. Adriaan; Spiga, Francesca; Staub, Daniel R.; Hale, Matthew W.; Shekhar, Anantha; Lowry, Christopher A.

2007-01-01

Serotonergic systems arising from the mid-rostrocaudal and caudal dorsal raphe nucleus (DR) have been implicated in the facilitation of anxiety-related behavioral responses by anxiogenic drugs or aversive stimuli. In this study we attempted to determine a threshold to engage serotonergic neurons in the DR following exposure to aversive conditions in an anxiety-related behavioral test. We manipulated the intensity of anxiogenic stimuli in studies of male Wistar rats by leaving them undisturbed (CO), briefly handling them (HA), or exposing them to an open-field arena for 15-min under low-light (LL: 8-13 lux) or high-light (HL: 400-500 lux) conditions. Rats exposed to HL conditions responded with reduced locomotor activity, reduced time spent exploring the center of the arena, a lower frequency of rearing and grooming, and an increased frequency of facing the corner of the arena compared to LL rats. Rats exposed to HL conditions had small but significant increases in c-Fos expression within serotonergic neurons in subdivisions of the rostral DR. Exposure to HL conditions did not alter c-Fos responses in serotonergic neurons in any other DR subdivision. In contrast, rats exposed to the open-field arena had increased c-Fos expression in non-serotonergic cells throughout the DR compared to CO rats, and this effect was particularly apparent in the dorsolateral part of the DR. We conclude that exposure to HL conditions, compared to LL conditions, increased anxiety-related behavioral responses in an open-field arena but this stimulus was at or below the threshold required to increase c-Fos expression in serotonergic neurons. PMID:17303505

Development of a bio-magnetic measurement system and sensor configuration analysis for rats

NASA Astrophysics Data System (ADS)

Kim, Ji-Eun; Kim, In-Seon; Kim, Kiwoong; Lim, Sanghyun; Kwon, Hyukchan; Kang, Chan Seok; Ahn, San; Yu, Kwon Kyu; Lee, Yong-Ho

2017-04-01

Magnetoencephalography (MEG) based on superconducting quantum interference devices enables the measurement of very weak magnetic fields (10-1000 fT) generated from the human or animal brain. In this article, we introduce a small MEG system that we developed specifically for use with rats. Our system has the following characteristics: (1) variable distance between the pick-up coil and outer Dewar bottom (˜5 mm), (2) small pick-up coil (4 mm) for high spatial resolution, (3) good field sensitivity (45 ˜ 80 fT /cm/√{Hz} ) , (4) the sensor interval satisfies the Nyquist spatial sampling theorem, and (5) small source localization error for the region to be investigated. To reduce source localization error, it is necessary to establish an optimal sensor layout. To this end, we simulated confidence volumes at each point on a grid on the surface of a virtual rat head. In this simulation, we used locally fitted spheres as model rat heads. This enabled us to consider more realistic volume currents. We constrained the model such that the dipoles could have only four possible orientations: the x- and y-axes from the original coordinates, and two tangentially layered dipoles (local x- and y-axes) in the locally fitted spheres. We considered the confidence volumes according to the sensor layout and dipole orientation and positions. We then conducted a preliminary test with a 4-channel MEG system prior to manufacturing the multi-channel system. Using the 4-channel MEG system, we measured rat magnetocardiograms. We obtained well defined P-, QRS-, and T-waves in rats with a maximum value of 15 pT/cm. Finally, we measured auditory evoked fields and steady state auditory evoked fields with maximum values 400 fT/cm and 250 fT/cm, respectively.

Sub-Acute Toxicity Study of Graphene Oxide in the Sprague-Dawley Rat.

PubMed

Li, Yingbo; Wang, Yan; Tu, Liu; Chen, Di; Luo, Zhi; Liu, Dengyuan; Miao, Zhuang; Feng, Gang; Qing, Li; Wang, Shali

2016-11-17

Graphene oxide (GO) is an oxidized derivative of graphene used in biotechnology and medicine. The safety of GO is uncertain, so we evaluated its toxicity in male rats. Rat tail veins were injected with 2.5, 5, or 10 mg/kg GO for seven days and behavioral patterns, pathology, and tissue morphology were assessed. Data show that behaviors were not altered according to an open field test and a functional observational battery test, but histopathological analysis indicated that GO caused inflammation of the lung, liver, and spleen. GO also reduced cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL). No other organs were modified. Thus, high concentrations of GO are toxic for the lung, liver, and spleen, but the mechanism by which this occurs requires more study.

Beaded-chain collars: A new method to radiotag kangaroo rats for short-term studies

USGS Publications Warehouse

Harker, M.B.; Rathbun, G.B.; Langtimm, C.A.

1999-01-01

To study burrow use by small mammals, we needed to develop a simple, non-invasive radiotag for the endangered giant kangaroo rat (Dipodomys ingens). We designed and tested a radiocollar made of beaded-chain on 4 captive Heermann's kangaroo rats (D. heermanii). Attachment of the collar required no anesthesia, the collar was easily fitted in 1-2 minutes, and it caused minimal stress to the animals. Once the collar design and attachment technique were perfected on the surrogate animals, we fitted radiocollars on 48 giant kangaroo rats for about 15 days. Upon recapture, 12 animals showed some minor fur or skin abrasion on the neck. Overall, the attachment performed as expected and proved to be a reliable method to radiotrack kangaroo rats during our short-term field study.

Emotional reactivity and cognitive performance in aversively motivated tasks: a comparison between four rat strains.

PubMed

van der Staay, F Josef; Schuurman, Teun; van Reenen, Cornelis G; Korte, S Mechiel

2009-12-15

Cognitive function might be affected by the subjects' emotional reactivity. We assessed whether behavior in different tests of emotional reactivity is correlated with performance in aversively motivated learning tasks, using four strains of rats generally considered to have a different emotional reactivity. The performance of male Brown Norway, Lewis, Fischer 344, and Wistar Kyoto rats in open field (OF), elevated plus-maze (EPM), and circular light-dark preference box (cLDB) tasks, which are believed to provide measures of emotional reactivity, was evaluated. Spatial working and reference memory were assessed in two aversively motivated learning and memory tasks: the standard and the "repeated acquisition" versions of the Morris water maze escape task, respectively. All rats were also tested in a passive avoidance task. At the end of the study, levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid, and 5-HT turnover in the hippocampus and frontal cortex were determined. Strain differences showed a complex pattern across behavioral tests and serotonergic measures. Fischer 344 rats had the poorest performance in both versions of the Morris water escape task, whereas Brown Norway rats performed these tasks very well but the passive avoidance task poorly. Neither correlation analysis nor principal component analysis provided convincing support for the notion that OF, EPM, and cLDB tasks measure the same underlying trait. Our findings do not support the hypothesis that the level of emotional reactivity modulates cognitive performance in aversively motivated tasks. Concepts such as "emotional reactivity" and "learning and memory" cannot adequately be tapped with only one behavioral test. Our results emphasize the need for multiple testing.

Behavioral and neurochemical effects of alpha lipoic acid associated with omega-3 in tardive dyskinesia induced by chronic haloperidol in rats.

PubMed

de Araújo, Dayane Pessoa; Camboim, Thaisa Gracielle Martins; Silva, Ana Patrícia Magalhães; Silva, Caio da Fonseca; de Sousa, Rebeca Canuto; Barbosa, Mabson Delâno Alves; Oliveira, Lucidio Clebeson; Cavalcanti, José Rodolfo Lopes de Paiva; Lucena, Eudes Euler de Souza; Guzen, Fausto Pierdoná

2017-07-01

Tardive dyskinesia (TD) is characterized by involuntary movements of the lower portion of the face being related to typical antipsychotic therapy. TD is associated with the oxidative imbalance in the basal ganglia. Lipoic acid (LA) and omega-3 (ω-3) are antioxidants acting as enzyme cofactors, regenerating antioxidant enzymes. This study aimed to investigate behavioral and neurochemical effects of supplementation with LA (100 mg/kg) and ω-3 (1 g/kg) in the treatment of TD induced by chronic use of haloperidol (HAL) (1 mg/kg) in rats. Wistar male rats were used, weighing between 180-200 g. The animals were treated chronically (31 days) with LA alone or associated with HAL or ω-3. Motor behavior was assessed by open-field test, the catalepsy test, and evaluation of orofacial dyskinesia. Oxidative stress was accessed by determination of lipid peroxidation and concentration of nitrite. LA and ω-3 alone or associated caused an improvement in motor performance by increasing locomotor activity in the open-field test and decreased the permanence time on the bar in the catalepsy test and decreased the orofacial dyskinesia. LA and ω-3 showed antioxidant effects, decreasing lipid peroxidation and nitrite levels. Thus, the use of LA associated with ω-3 reduced the extrapyramidal effects produced by chronic use of HAL.

Acute withdrawal but not long-term withdrawal from methamphetamine affects sexual behavior in female rats.

PubMed

Thibodeau, Rachel B; Ornelas, Laura C; Romero, Jordan; Memos, Nicoletta; Scheible, Matthew; Avila, Alfred; Schumacher, Abby; Navarro, April; Zimmermann, Karen; Cuenod, Bethany A; Frohardt, Russell J; Guarraci, Fay A

2013-02-01

The present study was designed to investigate the long-term effects of repeated methamphetamine (MA) exposure on sexual motivation in female rats tested after a period of drug abstinence. In Experiment 1, female subjects received three injections of MA (1.0mg/kg/day, every other day) or saline and were tested for paced mating behavior (where females could control the receipt of sexual stimulation from one male rat) 21 days after their last injection. In Experiment 2, female subjects received 12 consecutive injections of MA (1.0mg/kg/day) or saline and were tested for mate choice (where females could control the receipt of sexual stimulation from two male rats simultaneously) 6 days after their last injection. Experiment 3 was identical to Experiment 2 except that female subjects received no baseline mating test and were tested for mate choice 24h and 6 days after their last injection. Open field tests were conducted in each experiment to measure locomotor activity after repeated exposure to MA. Although repeated MA exposure increased locomotor activity, mating behavior was not facilitated after either a short (6 days) or long (21 days) period of drug abstinence. Nevertheless, sexual behavior was disrupted during the 24h acute withdrawal period. Therefore, although the present study found no evidence of cross-sensitization between female sexual behavior and MA after either a short or a long period of drug abstinence, sexual behavior in sexually naïve female rats is sensitive to the depressive state associated with acute withdrawal from MA. In conclusion, the results of the present study suggest that MA acts differently from other psychomotor stimulants, and that the effects of MA withdrawal on sexual behavior differ between male and female rats. Copyright © 2012 Elsevier Inc. All rights reserved.

The effects of heavy particle irradiation on exploration and response to environmental change

NASA Astrophysics Data System (ADS)

Casadesus, G.; Shukitt-Hale, B.; Cantuti-Castelvetri, I.; Rabin, B. M.; Joseph, J. A.

2004-01-01

Free radicals produced by exposure to heavy particles have been found to produce motor and cognitive behavioral toxicity effects in rats similar to those found during aging. The present research was designed to investigate the effects of exposure to 56Fe particles on the ability of male Sprague-Dawley rats to detect novel arrangements in a given environment. Using a test of spatial memory previously demonstrated to be sensitive to aging, open field activity and reaction to spatial and non-spatial changes were measured in a group that received a dose of 1.5 Gy ( n=10) of 56Fe heavy particle radiation or in non-radiated controls ( n=10). Animals irradiated with 1.5 Gy of 56Fe particles exhibited some age-like effects in rats tested, even though they were, for the most part, subtle. Animals took longer to enter, visited less and spent significantly less time in the middle and the center portions of the open field, independently of total frequency and duration of activity of both groups. Likewise, irradiated subjects spend significantly more time exploring novel objects placed in the open field than did controls. However, irradiated subjects did not vary from controls in their exploration patterns when objects in the open field were spatially rearranged. Thus, irradiation with a dose of 1.5 Gy of 56Fe high-energy particle radiation elicited age-like effects in general open field exploratory behavior, but did not elicit age-like effects during the spatial and non-spatial rearrangement tasks.

The effects of heavy particle irradiation on exploration and response to environmental change

NASA Technical Reports Server (NTRS)

Casadesus, G.; Shukitt-Hale, B.; Cantuti-Castelvetri, I.; Rabin, B. M.; Joseph, J. A.

2004-01-01

Free radicals produced by exposure to heavy particles have been found to produce motor and cognitive behavioral toxicity effects in rats similar to those found during aging. The present research was designed to investigate the effects of exposure to 56Fe particles on the ability of male Sprague-Dawley rats to detect novel arrangements in a given environment. Using a test of spatial memory previously demonstrated to be sensitive to aging, open field activity and reaction to spatial and non-spatial changes were measured in a group that received a dose of 1.5 Gy (n=10) of 56Fe heavy particle radiation or in non-radiated controls (n=10). Animals irradiated with 1.5 Gy of 56Fe particles exhibited some age-like effects in rats tested, even though they were, for the most part, subtle. Animals took longer to enter, visited less and spent significantly less time in the middle and the center portions of the open field, independently of total frequency and duration of activity of both groups. Likewise, irradiated subjects spend significantly more time exploring novel objects placed in the open field than did controls. However, irradiated subjects did not vary from controls in their exploration patterns when objects in the open field were spatially rearranged. Thus, irradiation with a dose of 1.5 Gy of 56Fe high-energy particle radiation elicited age-like effects in general open field exploratory behavior, but did not elicit age-like effects during the spatial and non-spatial rearrangement tasks. Published by Elsevier Ltd on behalf of COSPAR.

Altered behavior in experimental cortical dysplasia.

PubMed

Zhou, Fu-Wen; Rani, Asha; Martinez-Diaz, Hildabelis; Foster, Thomas C; Roper, Steven N

2011-12-01

Developmental delay and cognitive impairment are common comorbidities in people with epilepsy associated with malformations of cortical development (MCDs). We studied cognition and behavior in an animal model of diffuse cortical dysplasia (CD), in utero irradiation, using a battery of behavioral tests for neuromuscular and cognitive function. Fetal rats were exposed to 2.25 Gy external radiation on embryonic day 17 (E17). At 1 month of age they were tested using an open field task, a grip strength task, a grid walk task, inhibitory avoidance, an object recognition task, and the Morris water maze task. Rats with CD showed reduced nonlocomotor activity in the open field task and impaired motor coordination for grid walking but normal grip strength. They showed a reduced tendency to recognize novel objects and reduced retention in an inhibitory avoidance task. Water maze testing showed that learning and memory were impaired in irradiated rats for both cue discrimination and spatially oriented tasks. These results demonstrate significant deficits in cortex- and hippocampus-dependent cognitive functions associated with the diffuse abnormalities of cortical and hippocampal development that have been documented in this model. This study documents multimodal cognitive deficits associated with CD and can serve as the foundation for future investigations into the mechanisms of and possible therapeutic interventions for this problem. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Effects of Chailong Jieyu Pill on Behavior, Monoamine Neurotransmitters, and Corticosteroid Receptors in a Rat Model of Anxiety Disorder.

PubMed

Feng, Guang-Kui; Ma, Xian-Jun; Chen, Yin-Yi; Bian, Guang-Rong; Yang, Chao; Gu, Bao-Dong

2018-01-01

Chailong Jieyu Pill (CJP) is composed of Radix Bupleuri, Radix Scutellariae, Rhizoma Pinelliae Preparata, Radix Codonopsis, Radix Glycyrrhizae preparata , keel, Concha Ostreae, Concha Margaritifera Usta, Rhizoma Zingiberis Recens , and Fructus Jujubae . CJP has shown good clinical effects on improving anxiety disorders. However, as the mechanism underlying such benefits remains unclear, the aim of this study was to investigate the mechanism of action for CJP on anxiety-related behaviors in a rat model of anxiety disorder. After establishing a rat model of anxiety disorder using uncertain empty bottle stimulation, rats were divided into control, model, citalopram, low-dose CJP, and high-dose CJP groups. After 1 month of administration, effects of treatments on rat appearance, body weight, and open-field test scores were observed. In addition, hippocampal monoamine neurotransmitter (5-hydroxytryptamine, dopamine, and norepinephrine) contents were measured with an enzyme-linked immunosorbent assay, and mRNA expression of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) were measured with reverse transcription-polymerase chain reaction. CJP increased rat weight, and this effect was increased in the high-dose CJP group compared with the citalopram group ( P < 0.05). CJP also elevated open-field test scores compared with the citalopram group ( P < 0.05). While CJP decreased monoamine neurotransmitter contents in rat hippocampus, the regulatory effect of CJP on 5-hydroxytryptamine was reduced compared with citalopram ( P < 0.01). CJP upregulated GR mRNA expression in both low-dose ( P < 0.05) and high-dose ( P < 0.01) CJP groups, but only the latter significantly downregulated MR mRNA expression and showed enhanced effects compared with citalopram ( P < 0.05). Thus, CJP likely exerted its significant antianxiety effect by diminishing monoamine neurotransmitters and regulating mRNA expression of MR and GR in the hippocampus of our rat model of anxiety disorder.

Western-style diet induces insulin insensitivity and hyperactivity in adolescent male rats.

PubMed

Marwitz, Shannon E; Woodie, Lauren N; Blythe, Sarah N

2015-11-01

The prevalence of obesity in children and adolescents has increased rapidly over the past 30 years, as has the incidence of attention deficit hyperactivity disorder (ADHD). In 2012, it was found that overweight children have a twofold higher chance of developing ADHD than their normal weight counterparts. Previous work has documented learning and memory impairments linked to consumption of an energy-dense diet in rats, but the relationship between diet and ADHD-like behaviors has yet to be explored using animal models. Therefore, the purpose of this study was to explore the role of diet in the etiology of attention and hyperactivity disorders using a rat model of diet-induced obesity. Male Sprague-Dawley rats were fed either a control diet or a Western-style diet (WSD) for ten weeks, and specific physiological and behavioral effects were examined. Tail blood samples were collected to measure fasting blood glucose and insulin levels in order to assess insulin insensitivity. Rats also performed several behavioral tasks, including the open field task, novel object recognition test, and attentional set-shifting task. Rats exposed to a WSD had significantly higher fasting insulin levels than controls, but both groups had similar glucose levels. The quantitative insulin sensitivity check index (QUICKI) indicated the development of insulin resistance in WSD rats. Performance in the open field test indicated that WSD induced pronounced hyperactivity and impulsivity. Further, control diet animals were able to discriminate between old and novel objects, but the WSD animals were significantly impaired in object recognition. However, regardless of dietary condition, rats were able to perform the attentional set-shifting paradigm. While WSD impaired episodic memory and induced hyperactivity, attentional set-shifting capabilities are unaffected. With the increasing prevalence of both obesity and ADHD, understanding the potential links between the two conditions is of clinical relevance. Copyright © 2015 Elsevier Inc. All rights reserved.

[Focal cerebral ischemia in rats with estrogen deficiency and endothelial dysfunction].

PubMed

Litvinov, A A; Volotova, E V; Kurkin, D V; Logvinova, E O; Darmanyan, A P; Tyurenkov, I N

2017-01-01

To assess an effect of ovariectomy (OE) on the cerebral blood flow, endothelium-dependent vasodilation, neurological, cognitive and locomotor deficit as markers of brain damage after focal ischemia in rats. The study was conducted in 48 female Wistar rats. Ovariectomy was performed with ovaries and uterine body extirpation, cerebral ischemia was performed by middle cerebral artery occlusion (MCAO) in rats. To assess brain damage, Combs and Garcia scores, 'open field' test (OFT), 'extrapolatory escape test' (EET), 'passive avoidance test' (PAT), 'beam-walking test' were used. Cerebral blood flow was measured using ultrasonic flowmetry. After 7 days of MCAO, the cerebral blood flow in ovarioectomized animals was reduced by 20% compared to sham-ovariectomized animals. Ovariectomized animals with MCAO showed a three-fold endothelium-dependent vasodilation reduction (the reaction of cerebral vessels to the introduction of acetylcholine and N-L-arginine), indicating the presence of severe endothelial dysfunction. In ovarioectomized animals, the cerebral blood flow was reduced by 34% compared to sham-operated animals. MCAO and OE taken together resulted in more than 2-fold increase in neurological, motor disturbances, 3-fold decrease in motor activity of the animals in the OP test. Focal ischemia in ovarioectomized animals with endothelial dysfunction led to memory decrease by 1/5 fold in PAT and by 2-fold in EET.

[Effects of quercetin on the learning and memory ability of neonatal rats with hypoxic-ischemic brain damage].

PubMed

Huang, Jing-Jing; Liu, Xuan; Wang, Xing-Qi; Yang, Li-Hua; Qi, Da-Shi; Yao, Rui-Qin

2012-06-01

To study the effects of quercetin, a flavonoid, on the learning and memory ability of 3-day-old neonatal rats with hypoxic-ischemic brain white matter damage (WMD). Sixty 3-day-old Sprague-Dawley rats were randomly divided into four groups: control, WMD model,and quercetin treatment groups (20 and 40 mg/kg). There were 15 rats in each group. Rats in the WMD model and the two quercetin treatment groups were subjected to right common carotid artery ligation followed by 2 hrs of exposure to 8% O2 to induce periventricular white matter injury. After the operation quercetin was administered daily in the two quercetin treatment groups for 6 weeks. Six weeks later, Morris water maze and open-field tests were carried out to test memory and learning ability as well as behavior and cognition. From the second day of training, escape latency in the Morris water maze test was more prolonged in the WMD model group than in the control group (P<0.01). The escape latency in the two quercetin treatment groups was shortened significantly compared with the WMD model group (P<0.05). The WMD model group crossed the original platform fewer times compared with the control and quercetin treatment groups (P<0.05). The open-field test indicated that the number of rearings increased and time spent in the centre was extended in the WMD model group compared with the control group. Compared with the WMD model group, the number of rearings was significantly reduced (P<0.05) and time spent in the centre was significantly shortened in the quercetin treatment groups (P<0.05). Quercetin treatment can improve memory and learning ability as well as cognitive ability in neonates with WMD, suggesting that quercetin protects against WMD resulting from hypoxia-ischemia.

The effect of neonatal handling on adult feeding behavior is not an anxiety-like behavior.

PubMed

Silveira, P P; Portella, A K; Clemente, Z; Gamaro, G D; Dalmaz, C

2005-02-01

Brief periods of handling during the neonatal period have been shown to have profound and long-lasting physiological consequences. Previous studies performed in our laboratory have demonstrated that handling the pups during the neonatal period leads to increased sweet food ingestion in adult life. The objective of this study is to verify if this effect could be explained by the enhanced anxiety levels in these animals. Litters were divided in: (1) intact; (2) handled (10 min in an incubator/day) and (3) handled + tactile stimulation (10 min/day). Procedures were performed on days 1-10 after birth. When adults, rats were tested in the elevated plus maze apparatus, light dark exploration test and open field test. They were also tested for sweet food ingestion, being injected with 2 mg/kg diazepam or vehicle 60 min before the test. Handling and handling + tactile stimulation do not alter performance in the plus maze test, but handled rats presented more crossings in the light/dark exploration test and open field (two-way ANOVA). Females also spent more % time in the open arms in the plus maze and more time in the lit compartment in the light/dark test, presenting more crossings in both tests. Both treated rats (handled and handled + tactile stimulation groups) consumed more sweet food than intact ones (two-way ANOVA). When diazepam was injected prior to the measurement of sweet food ingestion, there was no effect of the drug. We suggest that handling during the neonatal period leads to plastic alterations in the central nervous system of these animals, causing an increased ingestion of palatable food in adult life, and this alteration does not express an anxiety-like behavior.

Venlafaxine inhibits apoptosis of hippocampal neurons by up-regulating brain-derived neurotrophic factor in a rat depression model

PubMed Central

Huang, Xiao; Mao, Yue-Shi; Li, Chao; Wang, Hao; Ji, Jian-Lin

2014-01-01

Objective: To study the effect of venlafaxine on the expression of brain-derived neurotrophic factor (BDNF) in rat hippocampal neurons, as well as its inhibitory effect on apoptosis of hippocampal neurons. Methods: Differences in behavioral ability between the depression model group and the Venlafaxine treatment group were observed using behavioral, sucrose-water and open field tests. The rat hippocampal tissue was sliced, stained and observed for BDNF distribution by immunohistochemistry. Apoptosis of hippocampal neurons was detected by TUNEL. BDNF expression in the hippocampal tissue was detected by Western blot. Injury and apoptosis of the hippocampal tissue were observed by electron microscopy. Results: Behavioral test showed that venlafaxine effectively improved the behavioral abilities of depressed rats. Immunohistochemistry showed that venlafaxine markedly increased the BDNF expression in the rat hippocampus. TUNEL showed that venlafaxine markedly inhibited apoptosis of hippocampal neurons, which was also confirmed by electron microscopic observation of the pathologic sections. Conclusion: Venlafaxine improved the expression of BDNF through working on PI3k/PKB/eNOS pathway and repressed the apoptosis of hippocampal neurons. PMID:25197330

Hypobaric Hypoxia Induces Depression-like Behavior in Female Sprague-Dawley Rats, but not in Males

PubMed Central

Bogdanova, Olena V.; Olson, Paul R.; Sung, Young-Hoon; D'Anci, Kristen E.; Renshaw, Perry F.

2015-01-01

Abstract Kanekar, Shami, Olena V. Bogdanova, Paul R. Olson, Young-Hoon Sung, Kristen E. D'Anci, and Perry F. Renshaw. Hypobaric hypoxia induces depression-like behavior in female Sprague-Dawley rats, but not males. High Alt Med Biol 16:52–60, 2015—Rates of depression and suicide are higher in people living at altitude, and in those with chronic hypoxic disorders like asthma, chronic obstructive pulmonary disorder (COPD), and smoking. Living at altitude exposes people to hypobaric hypoxia, which can lower rat brain serotonin levels, and impair brain bioenergetics in both humans and rats. We therefore examined the effect of hypobaric hypoxia on depression-like behavior in rats. After a week of housing at simulated altitudes of 20,000 ft, 10,000 ft, or sea level, or at local conditions of 4500 ft (Salt Lake City, UT), Sprague Dawley rats were tested for depression-like behavior in the forced swim test (FST). Time spent swimming, climbing, or immobile, and latency to immobility were measured. Female rats housed at altitude display more depression-like behavior in the FST, with significantly more immobility, less swimming, and lower latency to immobility than those at sea level. In contrast, males in all four altitude groups were similar in their FST behavior. Locomotor behavior in the open field test did not change with altitude, thus validating immobility in the FST as depression-like behavior. Hypobaric hypoxia exposure therefore induces depression-like behavior in female rats, but not in males. PMID:25803141

A novel herbal treatment reduces depressive-like behaviors and increases brain-derived neurotrophic factor levels in the brain of type 2 diabetic rats.

PubMed

Luo, Chun; Ke, Yuting; Yuan, Yanyan; Zhao, Ming; Wang, Fuyan; Zhang, Yisheng; Bu, Shizhong

2016-01-01

Radix Puerariae and hawthorn fruit have been demonstrated to treat diabetes. They offer potential benefits for preventing depression in diabetes. The aim of this study was to investigate whether the combination of Radix Puerariae and hawthorn fruit (CRPHF) could prevent depression in a diabetic rat model generated by feeding the rats with a high-fat diet and a low-dose streptozotocin (STZ). The CRPHF was provided by the Shanghai Chinese Traditional Medical University. Twenty-four rats were randomly divided into four groups: normal control, normal-given-CRPHF (NC), diabetic control, and diabetic-given-CRPHF (DC) groups. The type 2 diabetic model was created by feeding the rats with a high-fat diet for 4 weeks followed by injection of 25 mg/kg STZ. CRPHF was given at 2 g/kg/d to the rats of NC and DC groups by intragastric gavage daily for 4 weeks after the type 2 diabetic model was successfully created. Body weight, random blood glucose (RBG), oral glucose tolerance test, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured during the study. Depressive-like behavior was evaluated at the end of the treatment by using the open field test (OFT), the elevated plus-maze test (EPMT), locomotor activity test (LAT), and forced swimming test (FST). Levels of extracellular signal-regulated protein kinase (ERK) and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex were evaluated by using Western blot. 1) CRPHF reduced RBG and improved glucose tolerance in diabetic rats; 2) CRPHF reduced TC and TG but did not significantly change HDL-C or LDL-C in diabetic rats; 3) CRPHF reversed the loss in body weights observed in diabetic rats; 4) CRPHF reduced depressive-like behavior as measured by OFT, EPMT, LAT, and FST; 5) BDNF was upregulated, and ERK was activated in the prefrontal cortex of diabetic rats treated with CRPHF. CRPHF has the potential of preventing depression in patients with diabetes.

Studies into the anxiolytic actions of agomelatine in social isolation reared rats: Role of corticosterone and sex.

PubMed

Regenass, Wilmie; Möller, Marisa; Harvey, Brian H

2018-02-01

Anxiety disorders are severely disabling, while current pharmacological treatments are complicated by delayed onset, low remission rates and side-effects. Sex is also noted to contribute towards illness severity and treatment response. Agomelatine is a melatonin (MT 1 /MT 2 ) agonist and serotonin (5-HT 2C ) antagonist purported to be anxiolytic in clinical and some pre-clinical studies. We undertook a detailed analysis of agomelatine's anxiolytic activity in a neurodevelopmental model of anxiety, the social isolation reared rat. Rats received sub-chronic treatment with vehicle or agomelatine (40 mg/kg per day intraperitoneally at 16:00 h for 16 days), with behaviour analysed in the open field test, social interaction test and elevated plus maze. The contribution of corticosterone and sex was also studied. Social isolation rearing increased locomotor activity and reduced social interaction in the social interaction test, and was anxiogenic in the elevated plus maze in males and females. Agomelatine reversed these behaviours. Male and female social isolation reared rats developed anxiety-like behaviours to a similar degree, although response to agomelatine was superior in male rats. Social isolation rearing decreased plasma corticosterone in both sexes and tended to higher levels in females, although agomelatine did not affect corticosterone in either sex. Concluding, agomelatine is anxiolytic in SIR rats, although correcting altered corticosterone could not be implicated. Sex-related differences in the response to agomelatine are evident.

Effects of chronic forced-swim stress on behavioral properties in rats with neonatal repeated MK-801 treatment.

PubMed

Kawabe, Kouichi

2017-08-01

The two-hit hypothesis has been used to explain the onset mechanism of schizophrenia. It assumes that predisposition to schizophrenia is originally attributed to vulnerability in the brain which stems from genetic or early developmental factors, and that onset is triggered by exposure to later detrimental factors such as stress in adolescence or adulthood. Based on this hypothesis, the present study examined whether rats that had received neonatal repeated treatment with an N-methyl-d-aspartate (NMDA) receptor antagonist (MK-801), an animal model of schizophrenia, were vulnerable to chronic stress. Rats were treated with MK-801 (0.2mg/kg) or saline twice daily on postnatal days 7-20, and animals in the stress subgroups were subjected to 20days (5days/week×4weeks) of forced-swim stress in adulthood. Following this, behavioral tests (prepulse inhibition, spontaneous alternation, open-field, and forced-swim tests) were carried out. The results indicate that neonatal repeated MK-801 treatment in rats inhibits an increase in immobility in the forced-swim test after they have experienced chronic forced-swim stress. This suggests that rats that have undergone chronic neonatal repeated NMDA receptor blockade could have a reduced ability to habituate or adapt to a stressful situation, and supports the hypothesis that these rats are sensitive or vulnerable to stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes in the pattern of exploratory behavior are associated with the emergence of social dominance relationships in male rats.

PubMed

Arakawa, Hiroyuki

2006-01-01

This study examined the effect of the establishment of dominance relationships and subordination on exploratory behavior for both postpubertal and adult male rats. Prior to an open field test, subjects were housed either in isolation (IS) or in littermate pairs (PS) with mild dominance relationships without overt victory or defeat, or in pairs with clear hierarchical relationships as dominants (DOM) or subordinates (SUB). Stretch-attend postures and entries into the center area of the open-field were measured as an index of passive and active exploratory behavior, respectively, and crossings in the peripheral area were counted as activity. SUB rats, both postpubertal and adult, displayed less activity and lower levels of active exploratory behavior, whereas adult IS rats showed higher levels of active exploratory behavior compared to the other groups. Furthermore, both DOM and PS rats exhibited a more passive pattern of exploratory behavior in adulthood than in postpuberty. Thus the results show that an increase in the active exploratory pattern is inhibited by the establishment of social relationships among adult rats, while a decrease in activity is a primarily effect of subordination. The capacity to change exploratory patterns following subordination is found even in the postpubertal stage when adultlike social relationships have not yet appeared. Copyright 2005 Wiley Periodicals, Inc.

The effect of chronic stimulation of serotonin receptor type 7 on recognition, passive avoidance memory, hippocampal long-term potentiation, and neuronal apoptosis in the amyloid β protein treated rat.

PubMed

Shahidi, Siamak; Asl, Sara Soleimani; Komaki, Alireza; Hashemi-Firouzi, Nasrin

2018-05-01

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory impairment, neuronal death, and synaptic loss in the hippocampus. Long-term potentiation (LTP), a type of synaptic plasticity, occurs during learning and memory. Serotonin receptor type 7 (5-HTR7) activation is suggested as a possible therapeutic target for AD. The aim of the present study was to examine the effects of chronic treatment with the 5-HTR7 agonist, AS19, on cognitive function, memory, hippocampal plasticity, amyloid beta (Aβ) plaque accumulation, and apoptosis in an adult rat model of AD. AD was induced in rats using Aβ (single 1 μg/μL intracerebroventricular (icv) injection during surgery). The following experimental groups were included: control, sham-operated, Aβ + saline (1 μL icv for 30 days), and Aβ + AS19 (1 μg/μL icv for 30 days) groups. The animals were tested for cognition and memory performance using the novel object recognition and passive avoidance tests, respectively. Next, anesthetized rats were placed in a stereotaxic apparatus for electrode implantation, and field potentials were recorded in the hippocampal dentate gyrus. Lastly, brains were removed and Aβ plaques and neuronal apoptosis were evaluated using Congo red staining and TUNEL assay, respectively. Administration of AS19 in the Aβ rats increased the discrimination index of the novel object recognition test. Furthermore, AS19 treatment decreased time spent in the dark compartment during the passive avoidance test. AS19 also enhanced both the population spike (PS) amplitude and the field excitatory postsynaptic potential (fEPSP) slope evoked potentials of the LTP components. Aβ plaques and neuronal apoptosis were decreased in the AS19-treated Aβ rats. These results indicate that chronic treatment with a 5-HTR7 agonist can prevent Aβ-related impairments in cognition and memory performance by alleviating Aβ plaque accumulation and neuronal apoptosis, hence improving neuronal plasticity. AS19 may be useful as a therapeutic agent for AD.

Effect of tribulus terrestris saponins on behavior and neuroendocrine in chronic mild stress depression rats.

PubMed

Wang, Zhe; Zhang, Dongdong; Hui, Shan; Zhang, Yingjin; Hu, Suiyu

2013-04-01

To observe the effect of tribulus terrestris saponins (TTS) on behavior and neuroendocrine of chronic mild stress (CMS) depression rats. Thirty male Sprague-Dawley rats were randomly allocated to six groups: vehicle group, CMS group, CMS + fluoxetine group and CMS + TTS of low-dosage (0.375 g/kg), medium-dosage (0.75 g/kg) and high-dosage (2.25 g/kg) groups. All rats except the vehicle group singly housed and exposed an unpredicted sequence of mild stressors. The behavior of rats was detected by open-field test (OFT) and sucrose preference test (SPT). The concentration of corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH) in serum of the rats were detected by radioimmunoassay. The concentration of cortisol (CORT) in serum was detected by enzyme immunoassay. CMS procedure not only significantly decreased the scores of crossing, rears and grooming in OFT and the sucrose preference in SPT (all P < 0.01), but also markedly increased serum CRH and CORT levels (both P < 0.05). Treatment with TTS (0.75 and 2.25 g/kg) could significantly prevent all of these abnormalities induced by CMS (P < 0.05, P < 0.01). CMS can affect rat behavior and neuroendocrine and cause depression. TTS has the antagonism on CMS and produce antidepressive effects.

Five on one side: personal and social information in spatial choice.

PubMed

Brown, Michael F; Saxon, Marie E; Bisbing, Teagan; Evans, Jessica; Ruff, Jennifer; Stokesbury, Andrew

2015-03-01

To examine whether the outcome of a rat's own choices ("personal information") and the choice behavior of another rat ("social information") can jointly control spatial choices, rats were tested in an open field task in which they searched for food. For the rats of primary interest (Subject Rats), the baited locations were all on one side of the arena, but the specific locations baited and the side on which they occurred varied over trials. The Subject Rats were sometimes tested together with an informed "Model" rat that had learned to find food in the same five locations (all on the same side of the arena) on every trial. Unintended perceptual cues apparently controlled spatial choices at first, but when perceptual cues to food location were not available, choices were controlled by both personal information (allowing the baited side of the arena to be determined) and social information (allowing baited locations to be determined more precisely). This shows that control by personal and social information are not mutually exclusive and supports the view that these two kinds of information can be used flexibly and adaptively to guide spatial choices. This article is part of a Special Issue entitled: tribute to Tom Zentall. Copyright © 2015 Elsevier B.V. All rights reserved.

Chronic Co-species Housing Mice and Rats Increased the Competitiveness of Male Mice.

PubMed

Liu, Ying-Juan; Li, Lai-Fu; Zhang, Yao-Hua; Guo, Hui-Fen; Xia, Min; Zhang, Meng-Wei; Jing, Xiao-Yuan; Zhang, Jing-Hua; Zhang, Jian-Xu

2017-03-01

Rats are predators of mice in nature. Nevertheless, it is a common practice to house mice and rats in a same room in some laboratories. In this study, we investigated the behavioral and physiological responsively of mice in long-term co-species housing conditions. Twenty-four male mice were randomly assigned to their original raising room (control) or a rat room (co-species-housed) for more than 6 weeks. In the open-field and light-dark box tests, the behaviors of the co-species-housed mice and controls were not different. In a 2-choice test of paired urine odors [rabbit urine (as a novel odor) vs. rat urine, cat urine (as a natural predator-scent) vs. rabbit urine, and cat urine vs. rat urine], the co-species-housed mice were more ready to investigate the rat urine odor compared with the controls and may have adapted to it. In an encounter test, the rat-room-exposed mice exhibited increased aggression levels, and their urines were more attractive to females. Correspondingly, the levels of major urinary proteins were increased in the co-species-housed mouse urine, along with some volatile pheromones. The serum testosterone levels were also enhanced in the co-species-housed mice, whereas the corticosterone levels were not different. The norepinephrine, dopamine, and 5-HT levels in the right hippocampus and striatum were not different between the 2. Our findings indicate that chronic co-species housing results in adaptation in male mice; furthermore, it appears that long-term rat-odor stimuli enhance the competitiveness of mice, which suggests that appropriate predator-odor stimuli may be important to the fitness of prey animals. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Adult emotionality and neural plasticity as a function of adolescent nutrient supplementation in male rats.

PubMed

McCall, Nora; Mahadevia, Darshini; Corriveau, Jennifer A; Glenn, Melissa J

2015-03-14

The present study explored the effects of supplementing male rats with either choline, omega-3 fatty acids, or phytoestrogens, from weaning into early adulthood, on emotionality and hippocampal plasticity. Because of the neuroprotective properties of these nutrients, we hypothesized that they would positively affect both behavior and hippocampal function when compared to non-supplemented control rats. To test this hypothesis, male Sprague Dawley rats were assigned to one of four nutrient conditions after weaning: 1) control (normal rat chow); 2) choline (supplemented in drinking water); 3) omega 3 fatty acids (daily oral supplements); or 4) phytoestrogens (supplemented in chow). After 4weeks on their respective diets, a subset of rats began 3weeks of behavioral testing, while the remaining behaviorally naïve rats were sacrificed after 6weeks on the diets to assess numbers of adult-born hippocampal neurons using the immature neuron marker, doublecortin. The results revealed that choline supplementation affected emotional functioning; compared to rats in other diet conditions, rats in this group were less anxious in an open field and after exposure to predator odor and showed less behavioral despair after forced swimming. Similar behavioral findings were evident following supplementation with omega-3 fatty acids and phytoestrogen supplementation, though not on all tests and not to the same magnitude. Histological findings followed a pattern consistent with the behavioral findings: choline supplementation, followed by omega-3 fatty acid supplementation, but not phytoestrogen supplementation, significantly increased the numbers of new-born hippocampal neurons. Choline and omega-3 fatty acids have similar biological functions-affecting cell membranes, growth factor levels, and epigenetically altering gene transcription. Thus, the present findings suggest that targeting nutrients with these effects may be a viable strategy to combat adult psychopathologies. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of comfort food on food intake, anxiety-like behavior and the stress response in rats.

PubMed

Ortolani, D; Oyama, L M; Ferrari, E M; Melo, L L; Spadari-Bratfisch, R C

2011-07-06

It has been suggested that access to high caloric food attenuates stress response. The present paper investigates whether access to commercial chow enriched with glucose and fat, here referred to as comfort food alters behavioral, metabolic, and hormonal parameters of rats submitted to three daily sessions of foot-shock stress. Food intake, anxiety-like behaviors, and serum levels of insulin, leptin, corticosterone, glucose and triglycerides were determined. The rats submitted to stress decreased the intake of commercial chow, but kept unaltered the intake of comfort food. During the elevated plus maze (EPM) test, stressed rats increased the number of head dipping, entries into the open arms, as well as the time spent there, and decreased the number of stretched-attend posture and risk assessment. These effects of stress were independent of the type of food consumed. Non-stressed rats ingesting comfort food decreased risk assessment as well. Stress and comfort food increased time spent in the center of the open field and delayed the first crossing to a new quadrant. Stress increased the plasma level of glucose and insulin, and reduced triglycerides, although consumption of comfort food increases glucose, triglyceride and leptin levels; no effect on leptin level was associated to stress. The stress induced increase in serum corticosterone was attenuated when rats had access to comfort food. It was concluded that foot-shock stress has an anorexigenic effect that is independent of leptin and prevented upon access to comfort food. Foot-shock stress also has an anxiolytic effect that is potentiated by the ingestion of comfort food and that is evidenced by both EPM and open field tests. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of continuous vs. cycling estrogen replacement on the acquisition, retention and expression of place- and response-learning in the open-field tower maze.

PubMed

Lipatova, Olga; Byrd, Dennis; Green, John T; Toufexis, Donna J

2014-10-01

Estrogen has been shown to either enhance or impair learning and memory in female rats. The use of different experimental paradigms or estrogen treatment regimens may contribute to these disparate findings. In order to assess the effect of different estradiol (E2) treatments on several aspects of cognition, we trained ovariectomized female rats with either continuous, cycling, or vehicle E2 replacement, in an open-field tower maze task (OFTM) designed to test reference memory in a low-stress environment. In addition, in order to compare two distinct learning and memory systems, rats were trained to use either a dorsolateral striatum-based response type learning or a hippocampal-based place type learning to solve the maze. Results showed that cyclic, but not continuous, E2 replacement facilitated the acquisition of spatial memory in place-learners. Neither E2 regimen affected acquisition in response-learners. Additionally, when all experimental groups were performing at asymptote, rats were evaluated for performance stability by changing the location of their start position in the OFTM. Both regimens of E2 disrupted the expression of spatial memory in place-learners following the novel start position. However, E2 replacement protected ovariectomized female rats from the disruption of memory expression following a start position change in response-learners. Additionally all experimental groups performed equally well when tested following a 21-day period during which rats were absent from the maze. These results suggest that E2 fluctuation is particularly important in the acquisition of hippocampal-mediated spatial learning, and that hippocampal-based memory may be subject to disruption following environmental change, while striatum-based memory is subject to protection. Copyright © 2014 Elsevier Inc. All rights reserved.

Intracranial pancreatic islet transplantation increases islet hormone expression in the rat brain and attenuates behavioral dysfunctions induced by MK-801 (dizocilpine).

PubMed

Bloch, Konstantin; Gil-Ad, Irit; Tarasenko, Igor; Vanichkin, Alexey; Taler, Michal; Hornfeld, Shay Henry; Vardi, Pnina; Weizman, Abraham

2015-06-01

The treatment of rodents with non-competitive antagonist of the N-Methyl-D-aspartate (NMDA) receptor, MK-801 (dizocilpine), induces symptoms of psychosis, deficits in spatial memory and impairment of synaptic plasticity. Recent studies have suggested that insulin administration might attenuate the cognitive dysfunctions through the modulatory effect on the expression of NMDA receptors and on the brain insulin signaling. Intrahepatic pancreatic islet transplantation is known as an efficient tool for correcting impaired insulin signaling. We examined the capacity of syngeneic islets grafted into the cranial subarachnoid cavity to attenuate behavioral dysfunctions in rats exposed to MK-801. Animals were examined in the open field (OF) and the Morris Water Maze (MWM) tests following acute or subchronic administration of MK-801. We found well-vascularized grafted islets expressing insulin, glucagon and somatostatin onto the olfactory bulb and prefrontal cortex. Significantly higher levels of insulin were detected in the hippocampus and prefrontal cortex of transplanted animals compared to the non-transplanted rats. All animals expressed normal peripheral glucose homeostasis for two months after transplantation. OF tests revealed that rats exposed to MK-801 treatment, showed hyper-responsiveness in motility parameters and augmented center field exploration compared to intact controls and these effects were attenuated by the grafted islets. Moreover, in the MWM, the rats treated with MK-801 showed impairment of spatial memory that were partially corrected by the grafted islets. In conclusion, intracranial islet transplantation leads to the expression of islet hormones in the brain and attenuates behavioral and cognitive dysfunctions in rats exposed to MK-801 administration without altering the peripheral glucose homeostasis. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of rock wool on the lungs evaluated by magnetometry and biopersistence test

PubMed Central

Kudo, Yuichiro; Kotani, Makoto; Tomita, Masayuki; Aizawa, Yoshiharu

2009-01-01

Background Asbestos has been reported to cause pulmonary fibrosis, and its use has been banned all over the world. The related industries are facing an urgent need to develop a safer fibrous substance. Rock wool (RW), a kind of asbestos substitute, is widely used in the construction industry. In order to evaluate the safety of RW, we performed a nose-only inhalation exposure study in rats. After one-month observation period, the potential of RW fibers to cause pulmonary toxicity was evaluated based on lung magnetometry findings, pulmonary biopersistence, and pneumopathology. Methods Using the nose-only inhalation exposure system, 6 male Fischer 344 rats (6 to 10 weeks old) were exposed to RW fibers at a target fiber concentration of 100 fibers/cm3 (length [L] > 20 μm) for 6 hours daily, for 5 consecutive days. As a magnetometric indicator, 3 mg of triiron tetraoxide suspended in 0.2 mL of physiological saline was intratracheally administered after RW exposure to these rats and 6 unexposed rats (controls). During one second magnetization in 50 mT external magnetic field, all magnetic particles were aligned, and immediately afterwards the strength of their remanent magnetic field in the rat lungs was measured in both groups. Magnetization and measurement of the decay (relaxation) of this remanent magnetic field was performed over 40 minutes on 1, 3, 14, and 28 days after RW exposure, and reflected cytoskeleton dependent intracellular transport within macrophages in the lung. Similarly, 24 and 12 male Fisher 344-rats were used for biopersistence test and pathologic evaluation, respectively. Results In the lung magnetometric evaluation, biopersistence test and pathological evaluation, the arithmetic mean value of the total fiber concentration was 650.2, 344.7 and 390.7 fibers/cm3, respectively, and 156.6, 93.1 and 95.0 fibers/cm3 for fibers with L > 20 μm, respectively. The lung magnetometric evaluation revealed that impaired relaxation indicating cytoskeletal toxicity did not occur in the RW exposure group. In addition, clearance of the magnetic tracer particles was not significantly affected by the RW exposure. No effects on lung pathology were noted after RW exposure. Conclusion These findings indicate that RW exposure is unlikely to cause pulmonary toxicity within four weeks period. Lung magnetometry studies involving long-term exposure and observation will be necessary to ensure the safety of RW. PMID:19323845

Desert Rats 2011 Mission Simulation: Effects of Microgravity Operational Modes on Fields Geology Capabilities

NASA Technical Reports Server (NTRS)

Bleacher, Jacob E.; Hurtado, J. M., Jr.; Meyer, J. A.

2012-01-01

Desert Research and Technology Studies (DRATS) is a multi-year series of NASA tests that deploy planetary surface hardware and exercise mission and science operations in difficult conditions to advance human and robotic exploration capabilities. DRATS 2011 (Aug. 30-Sept. 9, 2011) tested strategies for human exploration of microgravity targets such as near-Earth asteroids (NEAs). Here we report the crew perspective on the impact of simulated microgravity operations on our capability to conduct field geology.

Comparing the impact of chronic energy restriction and vitamin E supplementation on the behavior of adult rats.

PubMed

Diniz, Derlange B; de Oliveira, Suzana L; Melo, Liana L; Amaya-Farfan, Jaime

2009-09-01

The purpose of this work was to investigate the influence of energy restriction and vitamin E supplementation on memory, learning, anxiety and spontaneous locomotion in adult rats. Three-month-old male Wistar rats were grouped according to diet: Control (AIN 93-M; n=18), Supplemented (AIN 93-M + 1425 IU all-rac-alpha-tocopheryl acetate/kg diet; n=22) and Restricted (AIN 93-M with 30% reduction in carbohydrate energy; n=23). Sixteen weeks after, the passive avoidance (PA), elevated plus-maze (EPM) and open field (OF) tests were applied. In the EPM test, the behavioral profile of the supplemented group was characterized by a lower frequency of entries into the open arms (P < 0,026), whereas the restricted group showed a lower frequency of head dipping (P < 0,003). The ratio between the time span of the shocks and the number of attempts were larger for the supplemented than for the non-supplemented animals (P = 0,0474), thus suggesting a delay in learning in the PA test. Taken together, these results suggest that a long-term combination of carbohydrate energy restriction in rats should not cause negative behavioral alterations. Compared with vitamin E supplementation, the restricted diet performed equally or better in rats as an alternate antioxidant diet.

Prohedonic Effect of Cannabidiol in a Rat Model of Depression.

PubMed

Shoval, Gal; Shbiro, Liat; Hershkovitz, Liron; Hazut, Noa; Zalsman, Gil; Mechoulam, Raphael; Weller, Aron

2016-01-01

Accumulating evidence suggests that cannabidiol (CBD) may be an effective and safe anxiolytic agent and potentially also an antidepressant. The objective of this study was to further examine these properties of CBD using the 'depressive-like' Wistar-Kyoto (WKY) rat, focusing on the drug's effect on anhedonia-like behaviors. Forty-eight WKY and 48 control Wistar adult male rats were pretreated orally with CBD (15, 30 and 45 mg/kg) or vehicle. The saccharin preference test (SPT), the elevated plus maze (EPM) test and the novel object exploration (NOE) test were used. CBD showed a prohedonic effect on the WKY rats at 30 mg/kg in the SPT. In the NOE, CBD increased exploration of the novel object and locomotion at 45 mg/kg and increased locomotion at 15 mg/kg, indicating an improvement in the characteristically low motivation of WKY rats to explore. There was no similar effect at any dose in the EPM or in open-field behavior in the habituation to the NOE. These findings extend the limited knowledge on the antidepressant effect of CBD, now shown for the first time in a genetic animal model of depression. These results suggest that CBD may be beneficial for the treatment of clinical depression and other states with prominent anhedonia. © 2016 S. Karger AG, Basel.

Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

PubMed Central

Homberg, Judith R.; Olivier, Jocelien D. A.; Blom, Tom; Arentsen, Tim; van Brunschot, Chantal; Schipper, Pieter; Korte-Bouws, Gerdien; van Luijtelaar, Gilles; Reneman, Liesbeth

2011-01-01

The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg) at postnatal day (PND) 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7–14 days after the last injection when (nor)fluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (nor)fluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling) immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential fluoxetine-induced neuroplasticity in the amygdala. PMID:21304948

Noopept reduces the postischemic functional and metabolic disorders in the brain of rats with different sensitivity to hypoxia.

PubMed

Zarubina, I V; Shabanov, P D

2009-03-01

Chronic cerebral ischemia was induced by ligation of both common carotid arteries in Wistar rats, divided by sensitivity to hypoxia into highly sensitive and low-sensitive. Noopept (peptide preparation), injected (0.5 mg/kg) during 7 days after occlusion of the carotid arteries, reduced the neurological disorders in rats with high and low sensitivity to hypoxia and improved their survival during the postischemic period. Noopept normalized behavior disordered by cerebral ischemia (according to the open field and elevated plus maze tests), prevented accumulation of LPO products and inhibition of antioxidant systems in the brain of rats with high and low sensitivity to hypoxia. Hence, noopept exhibited a neuroprotective effect in cerebral ischemia.

Antidepressant-like deliverables from the sea: evidence on the efficacy of three different brown seaweeds via involvement of monoaminergic system.

PubMed

Siddiqui, Pirzada Jamal Ahmed; Khan, Adnan; Uddin, Nizam; Khaliq, Saima; Rasheed, Munawwer; Nawaz, Shazia; Hanif, Muhammad; Dar, Ahsana

2017-07-01

Brown seaweeds exhibit several health benefits in treating and managing wide array of ailments. In this study, the antidepressant-like effect of methaolic extracts from Sargassum swartzii (SS), Stoechospermum marginatum (SM), and Nizamuddinia zanardinii (NZ) was examined in forced swimming test (FST), in rats. Oral administration of SS, SM, and NZ extract (30-60 mg/kg) exhibited antidepressant-like activity in FST by reducing immobility time as compared to control group, without inducing significant change in ambulatory behavior in open field test. In order to evaluate the involvement of monoaminergic system, rats were pretreated with the inhibitor of brain serotonin stores p-chlorophenylalanin (PCPA), dopamine (SCH23390 and sulpiride), and adrenoceptor (prazosin and propranolol) antagonists. Rats receiving treatment for 28 days were decapitated and brains were analyzed for monoamine levels. It may be concluded that the extracts of SS, SM, and NZ produces antidepressant-like activity via modulation of brain monoaminergic system in a rat model.

Digital Learning Network Education Events for the Desert Research and Technology Studies

NASA Technical Reports Server (NTRS)

Paul, Heather L.; Guillory, Erika R.

2007-01-01

NASA s Digital Learning Network (DLN) reaches out to thousands of students each year through video conferencing and webcasting. As part of NASA s Strategic Plan to reach the next generation of space explorers, the DLN develops and delivers educational programs that reinforce principles in the areas of science, technology, engineering and mathematics. The DLN has created a series of live education videoconferences connecting the Desert Research and Technology Studies (RATS) field test to students across the United States. The programs are also extended to students around the world via live webcasting. The primary focus of the events is the Vision for Space Exploration. During the programs, Desert RATS engineers and scientists inform and inspire students about the importance of exploration and share the importance of the field test as it correlates with plans to return to the Moon and explore Mars. This paper describes the events that took place in September 2006.

Differences in Monoamine Oxidase Activity in the Brain of Wistar and August Rats with High and Low Locomotor Activity: A Cytochemical Study.

PubMed

Sergutina, A V; Rakhmanova, V I

2016-06-01

Monoamine oxidase activity was quantitatively assessed by cytochemical method in brain structures (layers III and V of the sensorimotor cortex, caudate nucleus, nucleus accumbens, hippocampal CA3 field) of rats of August line and Wistar population with high and low locomotor activity in the open fi eld test. Monoamine oxidase activity (substrate tryptamine) predominated in the nucleus accumbens of Wistar rats with high motor activity in comparison with rats with low locomotor activity. In August rats, enzyme activity (substrates tryptamine and serotonin) predominated in the hippocampus of animals with high motor activity. Comparison of August rats with low locomotor activity and Wistar rats with high motor activity (i.e. animals demonstrating maximum differences in motor function) revealed significantly higher activity of the enzyme (substrates tryptamine and serotonin) in the hippocampus of Wistar rats. The study demonstrates clear-cut morphochemical specificity of monoaminergic metabolism based on the differences in the cytochemical parameter "monoamine oxidase activity", in the studied brain structures, responsible for the formation and realization of goal-directed behavior in Wistar and August rats.

Dexmedetomidine and propofol sedation requirements in an autistic rat model.

PubMed

Elmorsy, Soha A; Soliman, Ghada F; Rashed, Laila A; Elgendy, Hamed

2018-05-30

Autism is a challenging neurodevelopmental disorder. Previous clinical observations suggest altered sedation requirements for autistic children. Our study aimed to test this observation experimentally with an animal model and, to explore its possible mechanisms. Eight adult pregnant female Sprague Dawley rats were randomly selected into two groups. Four were injected with intraperitoneal sodium valproate on the gestational day 12 and four were injected with normal saline. On post-natal day 28 the newborn male rats were subjected to an open field test to confirm autistic features. Each rat was injected intraperitoneally with a single dose of propofol (50 mg/kg) or dexmedetomidine (0.2 mg/kg). Times to Loss of Righting Reflex (LORR) and to Return of Righting Reflex (RORR) were recorded. On the next day, all rats were re-sedated and their EEGs were recorded. The rats were sacrificed and hippocampal GABAA and glutamate NMDA receptor gene expression were assessed. Autistic rats showed significantly longer time to LORR and a shorter time to RORR compared to controls (Median time to LORR: 12.0 versus 5.0 for dexmedetomidine and 22.0 and 8.0 for propofol; p < 0.05). EEG showed a low frequency, high amplitude wave pattern two minutes after LORR in control rats. Autistic rats showed a high frequency, low amplitude awake pattern. Hippocampal GABAA receptor gene expression was significantly less in autistic rats and NMDA gene expression was greater. This study in rat supports the clinical observations of increased anesthetic sedative requirements in autistic children and proposes a mechanism for it.

The identification of metabolic disturbances in the prefrontal cortex of the chronic restraint stress rat model of depression.

PubMed

Liu, Lanxiang; Zhou, Xinyu; Zhang, Yuqing; Liu, Yiyun; Yang, Lining; Pu, Juncai; Zhu, Dan; Zhou, Chanjuan; Xie, Peng

2016-05-15

Major depressive disorder, with serious impairment in cognitive and social functioning, is a complex psychiatric disorder characterized by pervasive and persistent low mood and a loss of interest or pleasure. However, the underlying molecular mechanisms of depression remain largely unknown. In this study, we used a non-targeted metabolomics approach based on gas chromatography-mass spectrometry of the prefrontal cortex in chronic restraint stress (CRS)-treated rats. CRS was induced in the stress group by restraining rats in a plastic restrainer for 6h every day. This stress paradigm continued for 21 days. Body weight measurement and behavior tests were applied, including the sucrose preference test for anhedonia, the forced swimming test for despair-like behavior, and open field test and the elevated plus-maze to test for anxiety-like behaviors in rats after CRS. Differentially expressed metabolites associated with CRS-treated rats were identified by combining multivariate and univariate statistical analysis and corrected for multiple testing using the Benjamini-Hochberg procedure. A heat map of differential metabolites was constructed using Matlab. Ingenuity Pathways Analysis was applied to identify the predicted pathways and biological functions relevant to the bio-molecules of interest. Our findings showed that CRS induces depression-like behaviors and not anxiety-like behaviors. Thirty-six metabolites were identified as potential depression biomarkers involved in amino acid metabolism, energy metabolism and lipid metabolism, as well as a disturbance in neurotransmitters. Consequently, this study provides useful insights into the molecular mechanisms of depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Anti-inflammatory and neuroprotective effect of a phytoestrogen compound on rat microglia.

PubMed

Marotta, F; Mao, G S; Liu, T; Chui, D H; Lorenzetti, A; Xiao, Y; Marandola, P

2006-11-01

Ovariectomized Wistar rats received orally 15 mg/kg of a phytoestrogen compound (genistein, daidzein, glycitein, black cohosh, angelica sin., licorice, vitex agnus) for 2 weeks to test its ability to modulate inflammatory microglia response. Microglial proliferation was tested by trypan blue and by absorbance. Serial supernatant sampling was performed for 24 h to check TNF-alpha, IL-beta, IL-6, and TGF-beta. LPS caused a time course increase of all cytokines, with IL-beta and TNF-alpha peaking at the 12th hour, whereas IL-6 and TGF-beta peaked at the 24 h observation. Rats fed with the phytoestrogen displayed a significantly lower level of proinflammatory cytokines and a higher level of TGF-beta, as shown also by Western blot analysis. This finding may offer promise in the field of nutraceutical intervention.

Rats with congenital learned helplessness respond less to sucrose but show no deficits in activity or learning.

PubMed

Vollmayr, Barbara; Bachteler, Daniel; Vengeliene, Valentina; Gass, Peter; Spanagel, Rainer; Henn, Fritz

2004-04-02

Inbred rat strains for congenital learned helplessness (cLH) and for congenital resistance to learned helplessness (cNLH) were investigated as a model to study genetic predisposition to major depression. Congenitally helpless rats respond less to sucrose under a progressive ratio schedule. This is not confounded by locomotor hypoactivity: in contrast, cLH rats show a slight hyperactivity during the first 5 min of an open field test. cLH rats acquire operant responding to sucrose as readily as cNLH rats and exhibit normal memory acquisition and retrieval in the Morris water maze, thus ruling out general learning deficits as the cause of the decreased response to sucrose. Reduced total responses and reduced breaking points for sucrose in the cLH strain argue for anhedonia, which is an analogue to loss of pleasure essential for the diagnosis of major depressive episodes, and thus confirm the validity of congenitally learned helpless rats as a model of major depression.

Comparing performances of logistic regression and neural networks for predicting melatonin excretion patterns in the rat exposed to ELF magnetic fields.

PubMed

Jahandideh, Samad; Abdolmaleki, Parviz; Movahedi, Mohammad Mehdi

2010-02-01

Various studies have been reported on the bioeffects of magnetic field exposure; however, no consensus or guideline is available for experimental designs relating to exposure conditions as yet. In this study, logistic regression (LR) and artificial neural networks (ANNs) were used in order to analyze and predict the melatonin excretion patterns in the rat exposed to extremely low frequency magnetic fields (ELF-MF). Subsequently, on a database containing 33 experiments, performances of LR and ANNs were compared through resubstitution and jackknife tests. Predictor variables were more effective parameters and included frequency, polarization, exposure duration, and strength of magnetic fields. Also, five performance measures including accuracy, sensitivity, specificity, Matthew's Correlation Coefficient (MCC) and normalized percentage, better than random (S) were used to evaluate the performance of models. The LR as a conventional model obtained poor prediction performance. Nonetheless, LR distinguished the duration of magnetic fields as a statistically significant parameter. Also, horizontal polarization of magnetic fields with the highest logit coefficient (or parameter estimate) with negative sign was found to be the strongest indicator for experimental designs relating to exposure conditions. This means that each experiment with horizontal polarization of magnetic fields has a higher probability to result in "not changed melatonin level" pattern. On the other hand, ANNs, a more powerful model which has not been introduced in predicting melatonin excretion patterns in the rat exposed to ELF-MF, showed high performance measure values and higher reliability, especially obtaining 0.55 value of MCC through jackknife tests. Obtained results showed that such predictor models are promising and may play a useful role in defining guidelines for experimental designs relating to exposure conditions. In conclusion, analysis of the bioelectromagnetic data could result in finding a relationship between electromagnetic fields and different biological processes. (c) 2009 Wiley-Liss, Inc.

Anxiolytic-like effect of Aronia melanocarpa fruit juice in rats.

PubMed

Valcheva-Kuzmanova, S; Zhelyazkova-Savova, M

2009-12-01

The main biologically active constituents of Aronia melanocarpa fruit juice (AMFJ) are polyphenolics, amongst them flavonoids, mainly anthocyanins. The aim of the present study was to investigate the effects of AMFJ (5 and 10 mL/kg) on anxiety using the social interaction test, on locomotor activity in the open field test and on working memory in the object recognition test in rats. AMFJ showed an anxiolytic-like effect which was demonstrated by a dose-dependent increase in the time of active social contacts between the test partners. The effects of both AMFJ doses were comparable to the effect of diazepam (1 mg/kg). AMFJ neither changed significantly horizontal and vertical locomotor activity, nor did it adversely affect working memory. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

Emotional reactivity and cognitive performance in aversively motivated tasks: a comparison between four rat strains

PubMed Central

2009-01-01

Background Cognitive function might be affected by the subjects' emotional reactivity. We assessed whether behavior in different tests of emotional reactivity is correlated with performance in aversively motivated learning tasks, using four strains of rats generally considered to have a different emotional reactivity. Methods The performance of male Brown Norway, Lewis, Fischer 344, and Wistar Kyoto rats in open field (OF), elevated plus-maze (EPM), and circular light-dark preference box (cLDB) tasks, which are believed to provide measures of emotional reactivity, was evaluated. Spatial working and reference memory were assessed in two aversively motivated learning and memory tasks: the standard and the "repeated acquisition" versions of the Morris water maze escape task, respectively. All rats were also tested in a passive avoidance task. At the end of the study, levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid, and 5-HT turnover in the hippocampus and frontal cortex were determined. Results Strain differences showed a complex pattern across behavioral tests and serotonergic measures. Fischer 344 rats had the poorest performance in both versions of the Morris water escape task, whereas Brown Norway rats performed these tasks very well but the passive avoidance task poorly. Neither correlation analysis nor principal component analysis provided convincing support for the notion that OF, EPM, and cLDB tasks measure the same underlying trait. Conclusions Our findings do not support the hypothesis that the level of emotional reactivity modulates cognitive performance in aversively motivated tasks. Concepts such as "emotional reactivity" and "learning and memory" cannot adequately be tapped with only one behavioral test. Our results emphasize the need for multiple testing. PMID:20003525

Saikosaponin D relieves unpredictable chronic mild stress induced depressive-like behavior in rats: involvement of HPA axis and hippocampal neurogenesis.

PubMed

Li, Hong-Yan; Zhao, Ying-Hua; Zeng, Min-Jie; Fang, Fang; Li, Min; Qin, Ting-Ting; Ye, Lu-Yu; Li, Hong-Wei; Qu, Rong; Ma, Shi-Ping

2017-11-01

Saikosaponin D (SSD), a major bioactive component isolated from Radix Bupleuri, has been reported to exert neuroprotective properties. The present study was designed to investigate the anti-depressant-like effects and the potential mechanisms of SSD. Behavioural tests including sucrose preference test (SPT), open field test (OFT) and forced swim test (FST) were performed to study the antidepressant-like effects of SSD. In addition, we examined corticosterone and glucocorticoid receptor (GR) levels to evaluate hypothalamic-pituitary-adrenal (HPA) axis function. Furthermore, hippocampal neurogenesis was assessed by testing doublecortin (DCX) levels, and neurotrophic molecule levels were also investigated in the hippocampus of rats. We found that unpredictable chronic mild stress (UCMS) rats displayed lost body weight, decreased sucrose consumption in SPT, reduced locomotive activity in OFT, and increased immobility time in FST. Chronic treatment with SSD (0.75, 1.50 mg/kg) remarkably ameliorated the behavioral deficiency induced by UCMS procedure. SSD administration downregulated elevated serum corticosterone levels, as well as alleviated the suppression of GR expression and nuclear translocation caused by UCMS, suggesting that SSD is able to remit the dysfunction of HPA axis. In addition, Western blot and immunohistochemistry analysis showed that SSD treatment significantly increased the generation of neurons in the hippocampus of UCMS rats indicated by elevated DCX levels. Moreover, hippocampal neurotrophic molecule levels of UCMS rats such as phosphorylated cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were raised after SSD treatment. Together, Our results suggest that SSD opposed UCMS-induced depressive behaviors in rats, which was mediated, partially, by the enhancement of HPA axis function and consolidation of hippocampal neurogenesis.

Effects of heat stress on endocrine functions & behaviour in the pre-pubertal rat

PubMed Central

Mete, Fatih; Kilic, Ertugrul; Somay, Adnan; Yilmaz, Bayram

2012-01-01

Background & objectives: Heat stress related hyperthermia may cause damage to various organ systems. There are very few studies on the effects of hyperthermia on the endocrine system. We therefore, investigated effects of exogenously induced hyperthermia on adrenal, testicular and thyroid functions and behavioural alterations in pre-pubertal male Sprague-Dawley rats. Methods: Three groups of 30-day old rats (n=7 per group) were used. Body temperature was increased to 39°C (Group I) and 41°C (Group II) in a hyperthermia induction chamber for 30 min. The rats in the Group III served as control (36 °C). All animals received saline and were decapitated 48 h after the experiments. Serum free triiodothyronin (fT3), free thyroxine (fT4), total testosterone and dehydroepiandrosterone sulphate (DHEA-S) levels were determined by chemiluminescence assay, and corticosterone by enzyme immunoassay. Testes, pituitary and adrenal glands were dissected out and processed for histopathological examination. To assess activity and anxiety of the animals, the open field test and elevated-0-maze test, respectively, were used in all groups 24 h before (day 29) and after (day 31) hyperthermia induction. Results: Serum corticosterone levels (3.22±1.3) were significantly reduced in the 39°C (1.3±0.9) and 41°C (1.09±0.7) hyperthermia groups (P<0.01) compared to controls. Serum levels of thyroid hormones did not significantly differ among the groups. DHEA-S and testosterone values were below the limit of detection in all groups. Histopathological examination revealed that there was mild hydropic degeneration in the pituitary and adrenal glands. Apoptotic germ cells were seen in the seminiferous tubules of pre-pubertal male rats exposed to hyperthermia (41°C). Progression time in the open field test was significantly decreased and anxiety test scores increased in animals exposed to 39°C compared to the control group (P<0.01). These parameters were more pronounced in the 41°C hyperthermia group. Interpretation & conclusions: Our results show that heat exposure-induced stress may cause delayed reduction in serum corticosterone levels which may be associated with behavioural deficits in pre-pubertal male rats. PMID:22446867

Juvenile Taiep rats have shorter dendritic trees in the dorsal field of the hippocampus without spatial learning disabilities.

PubMed

Silva-Gómez, Adriana B; Bravo-Duran, Dolores A; Eguibar, Jose R; Cortes, Carmen

2018-06-01

Myelin mutant taiep rats show a progressive demyelination in the central nervous system due to an abnormal accumulation of microtubules in the cytoplasm and the processes on their oligodendrocytes. Demyelination is associated with electrophysiological alterations and the mutant had a progressive astrocytosis. The illness is associated with change in cytokine levels and in the expression of different nitric oxide synthase and concomitantly lipoperoxidation in several areas of the brain. However, until now there has been no detailed anatomical analysis of neurons in this mutant. The aim of this study was to analyze the dendritic morphology in the hippocampus using Golgi-Cox staining and spatial memory through Morris water maze test in young adult (3 months old) taiep rats and compare them with normal Sprague-Dawley. Our results showed that taiep rats have altered dendritic tree morphology in pyramidal neurons in the CA1 field of the hippocampus, but not in the CA3 region. These morphological changes did not produce a concomitant deficit in spatial memory acquisition or recall at this early stage of the disease. Our results suggest that impairment of dendritic morphology in the CA1 field of the hippocampus is a landmark of the pathology of this progressive multiple sclerosis model. © 2018 Wiley Periodicals, Inc.

Immediate and Long-Term Outcome of Acute H2S Intoxication Induced Coma in Unanesthetized Rats: Effects of Methylene Blue

PubMed Central

Sonobe, Takashi; Chenuel, Bruno; Cooper, Timothy K.; Haouzi, Philippe

2015-01-01

Background Acute hydrogen sulfide (H2S) poisoning produces a coma, the outcome of which ranges from full recovery to severe neurological deficits. The aim of our study was to 1- describe the immediate and long-term neurological effects following H2S-induced coma in un-anesthetized rats, and 2- determine the potential benefit of methylene blue (MB), a compound we previously found to counteract acute sulfide cardiac toxicity. Methods NaHS was administered IP in un-sedated rats to produce a coma (n = 34). One minute into coma, the rats received MB (4 mg/kg IV) or saline. The surviving rats were followed clinically and assigned to Morris water maze (MWM) and open field testing then sacrificed at day 7. Results Sixty percent of the non-treated comatose rats died by pulseless electrical activity. Nine percent recovered with neurological deficits requiring euthanasia, their brain examination revealed major neuronal necrosis of the superficial and middle layers of the cerebral cortex and the posterior thalamus, with variable necrosis of the caudate putamen, but no lesions of the hippocampus or the cerebellum, in contrast to the typical distribution of post-ischemic lesions. The remaining animals displayed, on average, a significantly less effective search strategy than the control rats (n = 21) during MWM testing. Meanwhile, 75% of rats that received MB survived and could perform the MWM test (P<0.05 vs non-treated animals). The treated animals displayed a significantly higher occurrence of spatial search than the non-treated animals. However, a similar proportion of cortical necrosis was observed in both groups, with a milder clinical presentation following MB. Conclusion In conclusion, in rats surviving H2S induced coma, spatial search patterns were used less frequently than in control animals. A small percentage of rats presented necrotic neuronal lesions, which distribution differed from post-ischemic lesions. MB dramatically improved the immediate survival and spatial search strategy in the surviving rats. PMID:26115032

Immediate and Long-Term Outcome of Acute H2S Intoxication Induced Coma in Unanesthetized Rats: Effects of Methylene Blue.

PubMed

Sonobe, Takashi; Chenuel, Bruno; Cooper, Timothy K; Haouzi, Philippe

2015-01-01

Acute hydrogen sulfide (H2S) poisoning produces a coma, the outcome of which ranges from full recovery to severe neurological deficits. The aim of our study was to 1--describe the immediate and long-term neurological effects following H2S-induced coma in un-anesthetized rats, and 2--determine the potential benefit of methylene blue (MB), a compound we previously found to counteract acute sulfide cardiac toxicity. NaHS was administered IP in un-sedated rats to produce a coma (n = 34). One minute into coma, the rats received MB (4 mg/kg i.v.) or saline. The surviving rats were followed clinically and assigned to Morris water maze (MWM) and open field testing then sacrificed at day 7. Sixty percent of the non-treated comatose rats died by pulseless electrical activity. Nine percent recovered with neurological deficits requiring euthanasia, their brain examination revealed major neuronal necrosis of the superficial and middle layers of the cerebral cortex and the posterior thalamus, with variable necrosis of the caudate putamen, but no lesions of the hippocampus or the cerebellum, in contrast to the typical distribution of post-ischemic lesions. The remaining animals displayed, on average, a significantly less effective search strategy than the control rats (n = 21) during MWM testing. Meanwhile, 75% of rats that received MB survived and could perform the MWM test (P<0.05 vs non-treated animals). The treated animals displayed a significantly higher occurrence of spatial search than the non-treated animals. However, a similar proportion of cortical necrosis was observed in both groups, with a milder clinical presentation following MB. In conclusion, in rats surviving H2S induced coma, spatial search patterns were used less frequently than in control animals. A small percentage of rats presented necrotic neuronal lesions, which distribution differed from post-ischemic lesions. MB dramatically improved the immediate survival and spatial search strategy in the surviving rats.

Establishment of a schizophrenic animal model through chronic administration of MK-801 in infancy and social isolation in childhood.

PubMed

Liu, Weiqing; Wang, Xiuyan; Hong, Wenjuan; Wang, Dong; Chen, Xiaogang

2017-02-01

Although an increasing amount of evidence supports a "two-hit" hypothesis for the neurodevelopmental model of schizophrenia, there has been no development in animal models to test this hypothesis. An animal model was established by chronic administration of 0.1, 0.3, and 0.5mg/kg MK-801 in P7-P21 rats followed by four weeks of social isolation in childhood and then five days of social housing. Animal behaviors were measured by the open field (OF) test, the novel object recognition (NOR) test, the prepulse inhibition (PPI) test, and the elevated plus maze (EPM) test. We found a significant decrease in the NOR index in adolescent rats compared to saline control rats when administering 0.5mg/kg of MK-801 (P=0.02). We found that social isolation had no significant effect on NOR index, though social isolation significantly increased the total distance traveled and significantly decreased the resting time in adolescent rats in the OF test (P<0.001 and P=0.003, respectively). In contrast, we observed that MK-801 administration showed no significant effects on either total distance traveled or resting time. Both MK-801 administration and social isolation had no significant effect on the percent of PPI and startle amplitudes in adolescent rats. Social isolation significantly reduced the open arm entries in adolescent rats in the EPM test (P=0.023), but it did not reduce the ratio to enter the open arms and the stay time in open arm. Administration of MK-801 showed no significant effect on the indexes of entering the open arms in the EPM test on adolescent rats. MK-801 intervention in infancy is associated with the damage of long-term visual memory, whereas social isolation in childhood is associated with the increased spontaneous activity and anxiety levels. Administration of MK-801 in infancy and social isolation in childhood are two independent factors on the neurodevelopmental defects. Copyright © 2017 Elsevier Inc. All rights reserved.

Chronopharmacological effects of growth hormone on the executive function and oxidative stress response in rats.

PubMed

Ferrari, Carlos K B; França, Eduardo L; Monteiro, Luciane A; Santos, Bruno L; Pereira-Junior, Alfredo; Honorio-França, Adenilda C

2017-01-01

To investigate the chronopharmacological effects of growth hormone on executive function and the oxidative stress response in rats. Fifty male Wistar rats (36-40 weeks old) had ad libitum access to water and food and were separated into four groups: diurnal control, nocturnal control, diurnal GH-treated, and nocturnal GH-treated animals. Levels of Cu, Zn superoxide dismutase (Cu, Zn-SOD), and superoxide release by spleen macrophages were evaluated. For memory testing, adaptation and walking in an open field platform was used. GH-treated animals demonstrated better performance in exploratory and spatial open-field tests. The latency time in both GH-treated groups was significantly lower compared with the latency time of the control groups. The diurnal GH treatment did not stimulate superoxide release but increased the CuZn-SOD enzyme levels. The nocturnal GH treatment did not influence the superoxide release and CuZn-SOD concentration. GH treatment also resulted in heart atrophy and lung hypertrophy. Growth hormone treatment improved the performance of executive functions at the cost of oxidative stress triggering, and this effect was dependent on the circadian period of hormone administration. However, GH treatment caused damaging effects such as lung hypertrophy and heart atrophy.

Chlorpyrifos induces anxiety-like behavior in offspring rats exposed during pregnancy.

PubMed

Silva, Jonas G; Boareto, Ana C; Schreiber, Anne K; Redivo, Daiany D B; Gambeta, Eder; Vergara, Fernanda; Morais, Helen; Zanoveli, Janaína M; Dalsenter, Paulo R

2017-02-22

Chlorpyrifos is a pesticide, member of the organophosphate class, widely used in several countries to manage insect pests on many agricultural crops. Currently, chlorpyrifos health risks are being reevaluated due to possible adverse effects, especially on the central nervous system. The aim of this study was to investigate the possible action of this pesticide on the behaviors related to anxiety and depression of offspring rats exposed during pregnancy. Wistar rats were treated orally with chlorpyrifos (0.01, 0.1, 1 and 10mg/kg/day) on gestational days 14-20. Male offspring behavior was evaluated on post-natal days 21 and 70 by the elevated plus-maze test, open field test and forced swimming test. The results demonstrated that exposure to 0.1, 1 or 10mg/kg/day of chlorpyrifos could induce anxiogenic-like, but not depressive-like behavior at post-natal day 21, without causing fetal toxicity. This effect was reversed on post-natal day 70. Copyright © 2017 Elsevier B.V. All rights reserved.

Magnolol treatment reversed the glial pathology in an unpredictable chronic mild stress-induced rat model of depression.

PubMed

Li, Lu-Fan; Yang, Jie; Ma, Shi-Ping; Qu, Rong

2013-07-05

Growing evidence indicates that glia atrophy contributes to the pathophysiology and the pathogenesis of major depressive disorder. Magnolol is the main constituent identified in the bark of Magnolia officinalis, which has been used for the treatment of mental disorders, including depression, in Asian countries. In this study, we investigated the antidepressant-like effect and the possible mechanisms of magnolol in rats subjected to unpredictable chronic mild stress (UCMS). The ameliorative effect of magnolol on depression symptoms was investigated through behavior tests, including sucrose preference test, open-field test and forced-swimming test. In addition, the levels of glial fibrillary acidic protein (GFAP), an astrocyte marker, in the hippocampus and prefrontal cortex were determined by immunohistochemistry, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR). Exposure to UCMS resulted in a decrease of behavioral activity, whereas magnolol (20, 40 mg/kg) and fluoxetine (20mg/kg) administration significantly reversed the depressive-like behaviors (P<0.05).Moreover, treatment with magnolol effectively increased GFAP mRNA and protein levels in UCMS rats. These results confirmed the antidepressant-like effect of magnolol, which maybe primarily mediated by reversing the glial atrophy in the UCMS rat brain. Copyright © 2013 Elsevier B.V. All rights reserved.

Cigarette Smoke and Nicotine Effects on Brain Proinflammatory Responses and Behavioral and Motor Function in HIV-1 Transgenic Rats

PubMed Central

Royal, Walter; Can, Adem; Gould, Todd D.; Guo, Ming; Huse, Jared; Jackson, Myles; Davis, Harry; Bryant, Joseph

2018-01-01

Cognitive impairment in HIV-1 infection is associated with the induction of chronic proinflammatory responses in the brains of infected individuals. The risk of HIV-related cognitive impairment is increased by cigarette smoking, which induces brain inflammation in rodent models. To better understand the role of smoking and the associated immune response on behavioral and motor function in HIV infection, wild-type F344 and HIV-1 transgenic (HIV1Tg) rats were exposed to either smoke from nicotine-containing (regular) cigarettes, smoke from nicotine-free cigarettes, or to nicotine alone. The animals were then tested using the rotarod test (RRT), the novel object recognition test (NORT), and the open field test (OFT). Subsequently, brain frontal cortex from the rats was analyzed for levels of TNF-α, IL-1, and IL-6. On the RRT, impairment was noted for F344 rats exposed to either nicotine-free cigarette smoke or nicotine alone and for F344 and HIV1Tg rats exposed to regular cigarette smoke. Effects from the exposures on the OFT were seen only for HIV1Tg rats, for which function was worse following exposure to regular cigarette smoke as compared to exposure to nicotine alone. Expression levels for all three cytokines were overall higher for HIV1Tg than for F344 rats. For HIV1Tg rats, TNF-α, IL-1, and IL-6 gene expression levels for all exposure groups were higher than for control rats. All F344 rat exposure groups also showed significantly increased TNF-α expression levels. However, for F344 rats, IL-1 expression levels were higher only for rats exposed to nicotine-free and nicotine-containing CS, and no increase in IL-6 gene expression was noted with any of the exposures as compared to controls. These studies, therefore, demonstrate that F344 and HIV1Tg rats show differential behavioral and immune effects from these exposures. These effects may potentially reflect differences in the responsiveness of the various brain regions in the two animal species as well as the result of direct toxicity mediated by the proinflammatory cytokines that are produced by HIV proteins and by other factors that are present in regular cigarette smoke. PMID:29644536

Rats with hippocampal lesion show impaired learning and memory in the ziggurat task: a new task to evaluate spatial behavior.

PubMed

Faraji, Jamshid; Lehmann, Hugo; Metz, Gerlinde A; Sutherland, Robert J

2008-05-16

Spatial tasks are widely used to determine the function of limbic system structures in rats. The present study used a new task designed to evaluate spatial behavior, the ziggurat task (ZT), to examine the performance of rats with widespread hippocampal damage induced by N-methyl-d-aspartic acid (NMDA). The task consisted of an open field containing 16 identical ziggurats (pyramid shaped towers) arranged at equal distances. One of the ziggurats was baited with a food reward. The task required rats to navigate through the open field by using a combination of distal and/or proximal cues in order to locate the food reward. The ability to acquire and recall the location of the goal (baited) ziggurat was tested in consecutive training sessions of eight trials per day for 10 days. The location of the goal ziggurat was changed every second day, requiring the rats to learn a total of five different locations. Several parameters, including latency to find the target, distance traveled, the number of visits to non-baited ziggurats (errors), and the number of returns were used as indices of learning and memory. Control rats showed a significant decrease in distance traveled and reduced latency in locating the goal ziggurat across trials and days, suggesting that they learned and remembered the location of the goal ziggurat. Interestingly, the hippocampal-damaged group moved significantly faster, and traveled longer distances compared to the control group. Significant differences were observed between these groups with respect to the number of errors and returns on test days. Day 11 served as probe day, in which no food reward was given. The controls spent more time searching for the food in the previous training quadrant compared to the hippocampal group. The findings demonstrate that the ZT is a sensitive and efficient dry task for measuring hippocampus-dependent spatial performance in rats requiring little training and not associated with some of the disadvantages of water tasks.

A role for galanin N-terminal fragment (1-15) in anxiety- and depression-related behaviors in rats.

PubMed

Millón, Carmelo; Flores-Burgess, Antonio; Narváez, Manuel; Borroto-Escuela, Dasiel O; Santín, Luis; Parrado, Concepción; Narváez, José Angel; Fuxe, Kjell; Díaz-Cabiale, Zaida

2014-10-31

Galanin (GAL) plays a role in mood regulation. In this study we analyzed the action of the active N-terminal fragment [GAL(1-15)] in anxiety- and depression-related behavioral tests in rats. The effect of GAL(1-15) was analyzed in the forced swimming test, tail suspension test, open field test, and light/dark test. The proximity of GAL1 and GAL2 receptors was examined with the proximity ligation assay (PLA). We tested the GAL receptors involved in GAL(1-15) effects with the GAL2 receptor antagonist M871 and with an in vivo model of siRNA GAL2 receptor knockdown or siRNA GAL1 receptor knockdown rats. The effects of GAL(1-15) were also studied in the cell line RN33B. GAL(1-15) induced strong depression-like and anxiogenic-like effects in all the tests. These effects were stronger than the ones induced by GAL. The involvement of the GAL2 receptor was demonstrated with M871 and with the siRNA GAL2 receptor knockdown rats. The PLA indicated the possible existence of GAL1 and GAL2 heteroreceptor complexes in the dorsal hippocampus and especially in the dorsal raphe nucleus. In the siRNA GAL1 receptor knockdown rats the behavioral actions of GAL(1-15) disappeared, and in the siRNA GAL2 receptor knockdown rats the reductions of the behavioral actions of GAL(1-15) was linked to a disappearance of PLA. In the cell line RN33B, GAL(1-15) decreased 5-HT immunoreactivity more strongly than GAL. Our results indicate that GAL(1-15) exerts strong depression-related and anxiogenic-like effects and may give the basis for the development of drugs targeting GAL1 and GAL2 heteroreceptor complexes in the raphe-limbic system for the treatment of depression and anxiety. © The Author 2015. Published by Oxford University Press on behalf of CINP.

A Role for Galanin N-Terminal Fragment (1–15) in Anxiety- and Depression-Related Behaviors in Rats

PubMed Central

Millón, Carmelo; Flores-Burgess, Antonio; Narváez, Manuel; Borroto-Escuela, Dasiel O.; Santín, Luis; Parrado, Concepción; Narváez, José Angel; Fuxe, Kjell

2015-01-01

Background: Galanin (GAL) plays a role in mood regulation. In this study we analyzed the action of the active N-terminal fragment [GAL(1–15)] in anxiety- and depression-related behavioral tests in rats. Methods: The effect of GAL(1–15) was analyzed in the forced swimming test, tail suspension test, open field test, and light/dark test. The proximity of GAL1 and GAL2 receptors was examined with the proximity ligation assay (PLA). We tested the GAL receptors involved in GAL(1–15) effects with the GAL2 receptor antagonist M871 and with an in vivo model of siRNA GAL2 receptor knockdown or siRNA GAL1 receptor knockdown rats. The effects of GAL(1–15) were also studied in the cell line RN33B. Results: GAL(1–15) induced strong depression-like and anxiogenic-like effects in all the tests. These effects were stronger than the ones induced by GAL. The involvement of the GAL2 receptor was demonstrated with M871 and with the siRNA GAL2 receptor knockdown rats. The PLA indicated the possible existence of GAL1 and GAL2 heteroreceptor complexes in the dorsal hippocampus and especially in the dorsal raphe nucleus. In the siRNA GAL1 receptor knockdown rats the behavioral actions of GAL(1–15) disappeared, and in the siRNA GAL2 receptor knockdown rats the reductions of the behavioral actions of GAL(1–15) was linked to a disappearance of PLA. In the cell line RN33B, GAL(1–15) decreased 5-HT immunoreactivity more strongly than GAL. Conclusions: Our results indicate that GAL(1–15) exerts strong depression-related and anxiogenic-like effects and may give the basis for the development of drugs targeting GAL1 and GAL2 heteroreceptor complexes in the raphe-limbic system for the treatment of depression and anxiety. PMID:25522404

Hyperforin alleviates mood deficits of adult rats suffered from early separation.

PubMed

Zhu, Minghui; Liu, Chunhua; Qin, Xuan; Yang, Zhuo

2015-11-03

In this study, we aimed to explore the effect of hyperforin (Hyp) on adult rats suffered from early separation. Wistar infant rats were randomly divided into three groups: control group (CON), early separation from parents group (ESP), and early separation from parents+treatment with 3mg/kg/day Hyp group (ESP+Hyp). Postnatal rats of ESP group and ESP+Hyp group were separated from their mothers for 6h every day on the 14th day after birth, and this separation lasted for 3 weeks, while rats of CON group had no separation. Hyperforin was intragastric administrated on the 21th day after birth, and lasted for 2 weeks in ESP+Hyp group. After separation, adult rats were evaluated by using the open field test (OFT), novelty suppressed feeding test (NSF) and forced swimming test (FST). In OFT, time spent in central grids was much shorter in ESP group compared with that of CON group. After treatment with hyperforin, time spent in central area was much longer compared with that of ESP group. In NSF, the feeding latency of ESP group was much longer than that of CON group. After treatment with hyperforin, the feeding latency was shorter compared with that of ESP group. In FST, score of ESP group was markedly higher than that of CON group. Interestingly, the score was obviously lower in ESP+Hyp group than that of ESP group. In conclusion, these results suggest that hyperforin is able to alleviate anxiety and remit depression in ESP rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Social defeat stress causes depression-like behavior with metabolite changes in the prefrontal cortex of rats.

PubMed

Liu, Yi-Yun; Zhou, Xin-Yu; Yang, Li-Ning; Wang, Hai-Yang; Zhang, Yu-Qing; Pu, Jun-Cai; Liu, Lan-Xiang; Gui, Si-Wen; Zeng, Li; Chen, Jian-Jun; Zhou, Chan-Juan; Xie, Peng

2017-01-01

Major depressive disorder is a serious mental disorder with high morbidity and mortality. The role of social stress in the development of depression remains unclear. Here, we used the social defeat stress paradigm to induce depression-like behavior in rats, then evaluated the behavior of the rats and measured metabolic changes in the prefrontal cortex using gas chromatography-mass spectrometry. Within the first week after the social defeat procedure, the sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM) and forced swim test (FST) were conducted to examine the depressive-like and anxiety-like behaviors. For our metabolite analysis, multivariate statistics were applied to observe the distribution of all samples and to differentiate the socially defeated group from the control group. Ingenuity pathway analysis was used to find the potential relationships among the differential metabolites. In the OFT and EPM, there were no significant differences between the two experimental groups. In the SPT and FST, socially defeated rats showed less sucrose intake and longer immobility time compared with control rats. Metabolic profiling identified 25 significant variables with good predictability. Ingenuity pathways analysis revealed that "Hereditary Disorder, Neurological Disease, Lipid Metabolism" was the most significantly altered network. Stress-induced alterations of low molecular weight metabolites were observed in the prefrontal cortex of rats. Particularly, lipid metabolism, amino acid metabolism, and energy metabolism were significantly perturbed. The results of this study suggest that repeated social defeat can lead to metabolic changes and depression-like behavior in rats.

White matter atrophy and myelinated fiber disruption in a rat model of depression.

PubMed

Gao, Yuan; Ma, Jing; Tang, Jing; Liang, Xin; Huang, Chun-Xia; Wang, San-Rong; Chen, Lin-Mu; Wang, Fei-Fei; Tan, Chuan-Xue; Chao, Feng-Lei; Zhang, Lei; Qiu, Xuan; Luo, Yan-Min; Xiao, Qian; Du, Lian; Xiao, Qian; Tang, Yong

2017-06-01

Brain imaging and postmortem studies have indicated that white matter abnormalities may contribute to the pathology and pathogenesis of depression. However, until now, no study has quantitatively investigated white matter changes in depression in rats. The current study used the chronic unpredictable stress (CUS) model of depression. Body weight and sucrose preference test (SPT) scores were assessed weekly. Upon successfully establishing the CUS animal model, all animals were tested using the SPT and the open field test (OFT). Then, transmission electron microscopy and unbiased stereological methods were used to investigate white matter changes in the rats. Compared with the control group, the body weight and sucrose preference of the CUS rats were significantly decreased (p < .001, p < .001, respectively). In the OFT, the total time spent and the total distance traveled in the inner area by the CUS rats were significantly lower than those of the control group (p = .002, p = .001, respectively). The stereological results revealed that white matter volume, the total volume, and the total length and mean diameter of myelinated fibers in the white matter of the CUS rats were significantly decreased compared to the control rats (p = .042, p = .038, p = .035, p = .019, respectively). The results of this study suggested that white matter atrophy and disruption of myelinated fibers in the white matter may contribute to the pathophysiology underlying depression, which might provide new targets for the development of novel therapeutic interventions for depression. © 2017 Wiley Periodicals, Inc.

Activation of adenosine A(1) receptors alters behavioral and biochemical parameters in hyperthyroid rats.

PubMed

Bruno, Alessandra Nejar; Fontella, Fernanda Urruth; Bonan, Carla Denise; Barreto-Chaves, Maria Luiza M; Dalmaz, Carla; Sarkis, João José Freitas

2006-02-28

Adenosine acting on A(1) receptors has been related with neuroprotective and neuromodulatory actions, protection against oxidative stress and decrease of anxiety and nociceptive signaling. Previous studies demonstrated an inhibition of the enzymes that hydrolyze ATP to adenosine in the rat central nervous system after hyperthyroidism induction. Manifestations of hyperthyroidism include increased anxiety, nervousness, high O(2) consumption and physical hyperactivity. Here, we investigated the effects of administration of a specific agonist of adenosine A(1) receptor (N(6)-cyclopentyladenosine; CPA) on nociception, anxiety, exploratory response, locomotion and brain oxidative stress of hyperthyroid rats. Hyperthyroidism was induced by daily intraperitoneal injections of l-thyroxine (T4) for 14 days. Nociception was assessed with a tail-flick apparatus and exploratory behavior, locomotion and anxiety were analyzed by open-field and plus-maze tests. We verified the total antioxidant reactivity (TAR), lipid peroxide levels by the thiobarbituric acid reactive species (TBARS) reaction and the free radicals content by the DCF test. Our results demonstrated that CPA reverted the hyperalgesia induced by hyperthyroidism and decreased the exploratory behavior, locomotion and anxiety in hyperthyroid rats. Furthermore, CPA decreased lipid peroxidation in hippocampus and cerebral cortex of control rats and in cerebral cortex of hyperthyroid rats. CPA also increased the total antioxidant reactivity in hippocampus and cerebral cortex of control and hyperthyroid rats, but the production of free radicals verified by the DCF test was changed only in cerebral cortex. These results suggest that some of the hyperthyroidism effects are subjected to regulation by adenosine A(1) receptor, demonstrating the involvement of the adenosinergic system in this pathology.

Impulsive Choice, Alcohol Consumption, and Pre-Exposure to Delayed Rewards: II. Potential Mechanisms

PubMed Central

Stein, Jeffrey S.; Renda, C. Renee; Hinnenkamp, Jay E.; Madden, Gregory J.

2014-01-01

In a prior study (Stein et al., 2013), we reported that rats pre-exposed to delayed rewards made fewer impulsive choices, but consumed more alcohol (12% wt/vol), than rats pre-exposed to immediate rewards. To understand the mechanisms that produced these findings, we again pre-exposed rats to either delayed (17.5 s; n = 32) or immediate (n = 30) rewards. In post-tests, delay-exposed rats made significantly fewer impulsive choices at both 15- and 30-s delays to a larger, later food reward than the immediacy-exposed comparison group. Behavior in an open-field test provided little evidence of differential stress exposure between groups. Further, consumption of either 12% alcohol or isocaloric sucrose in subsequent tests did not differ between groups. Because Stein et al. introduced alcohol concentration gradually (3–12%), we speculate that their group differences in 12% alcohol consumption were not determined by alcohol’s pharmacological effects, but by another variable (e.g., taste) that was preserved as an artifact from lower concentrations. We conclude that pre-exposure to delayed rewards generalizes beyond the pre-exposure delay; however, this same experimental variable does not robustly influence alcohol consumption. PMID:25418607

[Sucrose reward promotes rats' motivation for cocaine].

PubMed

Li, Yan-Qing; LE, Qiu-Min; Yu, Xiang-Chen; Ma, Lan; Wang, Fei-Fei

2016-06-25

Caloric diet, such as fat and sugar intake, has rewarding effects, and has been indicated to affect the responses to addictive substances in animal experiments. However, the possible association between sucrose reward and the motivation for addictive drugs remains to be elucidated. Thus, we carried out behavioral tests after sucrose self-administration training to determine the effects of sucrose experience on rats' motivation for cocaine, locomotor sensitivity to cocaine, basal locomotor activity, anxiety level, and associative learning ability. The sucrose-experienced (sucrose) group exhibited higher lever press, cocaine infusion and break point, as well as upshift of cocaine dose-response curve in cocaine self-administration test, as compared with the control (chow) group. Additionally, despite similar locomotor activity in open field test and comparable score in cocaine-induced conditioned place preference, the sucrose group showed higher cocaine-induced locomotor sensitivity as compared with the chow group. The anxiety level and the performance in vocal-cue induced fear memory were similar between these two groups in elevated plus maze and fear conditioning tests, respectively. Taken together, our work indicates that sucrose experience promotes the rats' motivation for cocaine.

Managing Science Operations during Planetary Surface Operations at Long Light Delay-Time Targets: The 2011 Desert RATS Test

NASA Technical Reports Server (NTRS)

Eppler, D. B.

2012-01-01

Desert Research and Technology Studies (Desert RATS) is a multi-year series of hardware and operations tests carried out annually in the high desert of Arizona in the San Francisco Volcanic Field. Conducted since 1997, these activities are designed to exercise planetary surface hardware and operations in conditions where multi-day tests are achievable. Desert RATS 2011 Science Operations Test simulated the management of crewed science operations at targets that were beyond the light delay time experienced during Low-Earth Orbit (LEO) and lunar surface missions, such as a mission to a Near-Earth Object (NEO) or the martian surface. Operations at targets at these distances are likely to be the norm as humans move out of the Earth-Moon system. Operating at these distances places significant challenges on mission operations, as the imposed light-delay time makes normal, two-way conversations extremely inefficient. Consequently, the operations approach for space missions that has been exercised during the first half-century of human space operations is no longer viable, and new approaches must be devised.

Anxiety-like behaviour in adult rats perinatally exposed to maternal calorie restriction.

PubMed

Levay, Elizabeth A; Paolini, Antonio G; Govic, Antonina; Hazi, Agnes; Penman, Jim; Kent, Stephen

2008-08-22

Environmental stimuli such as caloric availability during the perinatal period exert a profound influence on the development of an organism. Studies in this domain have focused on the effects of under- and malnutrition while the effects of more mild levels of restriction have not been delineated. Rat dams and their offspring were subjected to one of five dietary regimens: control, CR50% for 3 days preconception, CR25% during gestation, CR25% during lactation, and CR25% during gestation, lactation, and post-weaning (lifelong). The pup retrieval test and maternal observations were conducted during lactation to quantify maternal care. In the pup retrieval test, dams that were concurrently experiencing CR (i.e., from the lactation and lifelong groups) displayed shorter latencies to retrieve all pups than the control and preconception groups and the lactation group constructed better nests than all groups. Adult offspring were tested in three tests of anxiety: the elevated plus maze, open field, and emergence test. No differences were observed in the elevated plus maze; however, in the open field preconception animals made fewer entries and spent more time in the central zone than controls. In addition, preconception offspring exhibited longer latencies to full body emergence, spent less time fully emerged, and spent more time engaged in risk assessment behaviours than all other groups. Offspring from the preconception group were also on average 11% heavier than control rats throughout life and displayed 37% higher serum leptin concentrations than controls. A potential role for leptin in the anxiogenic effect of preconception CR is discussed.

The antidepressant effects of rosiglitazone on rats with depression induced by neuropathic pain.

PubMed

Zong, Jian; Liao, Xingzhi; Ren, Bingxu; Wang, Zhiping

2018-06-15

A growing number of studies reported that rosiglitazone (a PPARgamma agonist) could ameliorate the painful state and prevent stress-induced depression. However, whether rosiglitazone can prevent pain-induced depression is unclear. This study aimed to explore the antidepressant effects of rosiglitazone in L5 spinal nerve transection (SNT) induced neuropathic pain rats. In addition, AMPK inhibitor (Compound C) and autophagic antagonist (3-methyladenine, 3-MA) were applied to investigate the underlying therapeutic mechanisms. L5 SNT-induced neuropathic pain symptoms and depressive like-behaviors were detected by paw pressure threshold test (PPT), open-field test (OFT), forced swimming test (FST), tail suspension test (TST), sucrose preference test (SPT). Rosiglitazone could ameliorate L5 SNT-induced neuropathic pain symptoms and depressive like-behaviors and the effect could be reversed by Compound C or 3-MA. Compared with the sham group, the levels of BDNF, AMPK, Beclin-1 and LC3B in rats hippocampus significantly decreased in L5 SNT group. On the contrary, rosiglitazone administration significantly up-regulated the levels of AMPK, BDNF, Beclin-1 and LC3B in rats hippocampus. Compared with sham group, the levels of TNF-α, IL-1β, superoxide dismutase (SOD) and malondialdehyde (MDA) in rat hippocampus significantly increased in L5 SNT group. Besides, rosiglitazone administration significantly decreased the levels of TNF-α, IL-1β, SOD and MDA in hippocampus. Compared with rosiglitazone group, 3-MA administration, but not Compound C administration, significantly increased the levels of TNF-α, IL-1β, SOD and MDA in hippocampus. In conclusion, rosiglitazone can counteract down-regulation of AMPK and BDNF induced by L5 SNT rats in hippocampus, and activate autophagic pathway. These effects may contribute to the antidepressant effect of rosiglitazone on the rats with depression induced by L5 SNT. Copyright © 2018 Elsevier Inc. All rights reserved.

Metabolomics identifies perturbations in amino acid metabolism in the prefrontal cortex of the learned helplessness rat model of depression.

PubMed

Zhou, Xinyu; Liu, Lanxiang; Zhang, Yuqing; Pu, Juncai; Yang, Lining; Zhou, Chanjuan; Yuan, Shuai; Zhang, Hanping; Xie, Peng

2017-02-20

Major depressive disorder is a serious psychiatric condition associated with high rates of suicide and is a leading cause of health burden worldwide. However, the underlying molecular mechanisms of major depression are still essentially unclear. In our study, a non-targeted gas chromatography-mass spectrometry-based metabolomics approach was used to investigate metabolic changes in the prefrontal cortex of the learned helplessness (LH) rat model of depression. Body-weight measurements and behavioral tests including the active escape test, sucrose preference test, forced swimming test, elevated plus-maze and open field test were used to assess changes in the behavioral spectrum after inescapable footshock stress. Rats in the stress group exhibited significant learned helpless and depression-like behaviors, while without any significant change in anxiety-like behaviors. Using multivariate and univariate statistical analysis, a total of 18 differential metabolites were identified after the footshock stress protocol. Ingenuity Pathways Analysis and MetaboAnalyst were applied for predicted pathways and biological functions analysis. "Amino Acid Metabolism, Molecule Transport, Small Molecule Biochemistry" was the most significantly altered network in the LH model. Amino acid metabolism, particularly glutamate metabolism, cysteine and methionine metabolism, arginine and proline metabolism, was significantly perturbed in the prefrontal cortex of LH rats. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of maternal separation on the neurobehavioral development of newborn Wistar rats.

PubMed

Farkas, Jozsef; Reglodi, Dora; Gaszner, Balazs; Szogyi, Donat; Horvath, Gabor; Lubics, Andrea; Tamas, Andrea; Frank, Falko; Besirevic, Dario; Kiss, Peter

2009-05-29

Animal models of neonatal stress, like maternal separation, may provide important correlation with human stress-related disorders. Early maternal deprivation has been shown to cause several short- and long-term neurochemical and behavioral deficits. Little is known about the early neurobehavioral development after postnatal stress. The aim of the present study was to investigate the development of reflexes and motor coordination in male and female pups subjected to maternal deprivation. Pups were removed from their mothers from postnatal day 1-14, for 3h daily. Somatic development (weight gain, eye opening, ear unfolding, incisor eruption) and reflex development was tested during the first 3 weeks. The appearance of the following reflexes was investigated: crossed extensor, grasping, placing, gait, righting and sensory reflexes, and negative geotaxis. Timely performance of negative geotaxis, righting and gait were also tested daily during the first 3 weeks. Motor coordination and open-field tests were performed on postnatal weeks 3-5 (rotarod, elevated grid-walk, footfault, rope suspension, inclined board and walk initiation tests). The results revealed that a 3-h-long daily maternal separation did not lead to a marked delay or enhancement in reflex development and motor coordination. A subtle enhancement was observed in the appearance of hindlimb grasp and gait reflexes, and a better performance in footfault test in male rats suffering from maternal deprivation. In contrast, female maternally deprived (MD) rats displayed a slight delay in forelimb grasp and air righting reflex appearance, and surface righting performance. Open-field activity was not changed in maternally deprived rats. In summary, our present observations indicate that maternal deprivation does not induce drastic changes in early neurodevelopment, therefore, further research is needed to determine the onset of behavioral alterations in subject with maternal deprivation history. Gender differences described in this study could help to understand how gender-specific differences in early life experience-induced stress-related disorders appear in adult life.

The Effects of rhBMP-2 Used for Spinal Fusion on Spinal Cord Pathology After Traumatic Injury

DTIC Science & Technology

2009-07-29

1219-1224; discussion 1225. Basso DM , Beattie MS, Bresnahan JC (1995) A sensitive and reliable locomotor rating scale for open field testing in rats...usage of rhBMP-2 in the anterior cervical spine. Spine 31:2813-2819. Stuesse SL, Crisp T, McBurney DL, Schechter JB, Lovell JA, Cruce WL (2001...250-256. Stuesse SL, Crisp T, McBurney DL, Schechter JB, Lovell JA, Cruce WL (2001) Neuropathic pain in aged rats: behavioral responses and

Metabolomic Changes in Rat Model of Cauda Equina Injury.

PubMed

Liu, Yang; Yang, Rui; Kong, Qingjie; Wang, Yuan; Zhang, Bin; Sun, Jingchuan; Yang, Yong; Zheng, Bing; Yuan, Hongbin; Shi, Jiangang

2017-06-01

To show the differences of metabolomic changes in a rat model of cauda equina injury (CEI) and find potent metabolic biomarkers of CEI. A total of 28 Sprague-Dawley rats were used in this study. After the rats were given anesthesia and fixed in a prone position, a piece of silicone block was placed into the epidural space below the lamina. Behavior tests including the Basso, Beattie, and Bresnahan open field locomotor scale and an inclined plane test were conducted 1 day and 2 days after surgery. The cauda equina tissue was collected 12 hours, 1 day, and 2 days after surgery. Ultraperformance liquid chromatography coupled with quadruple time-of-flight mass spectrometry was used for a quantitative analysis of cauda equine metabolic changes in rats from different groups. The differences between the metabolic profiles of the rats in 4 groups were analyzed using partial least squares discriminant analysis. In behavior tests and histologic analyses given 2 days after surgery, the animals showed remarkable organ dysfunction and pathologic damage. Metabolic profiles showed remarkable differences between the control and model groups. Thirty-four potential CEI metabolite biomarkers were identified between the control group and different time-point model groups. These potential biomarkers appeared in 15 metabolic pathways. Our results may improve the cause of CEI and provide a basis for clinical diagnosis and locating biomarkers in the early stages of the pathologic process of CEI. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurodegeneration caused by expression of human truncated tau leads to progressive neurobehavioural impairment in transgenic rats.

PubMed

Hrnkova, Miroslava; Zilka, Norbert; Minichova, Zuzana; Koson, Peter; Novak, Michal

2007-01-26

Human truncated tau protein is an active constituent of the neurofibrillary degeneration in sporadic Alzheimer's disease. We have shown that modified tau protein, when expressed as a transgene in rats, induced AD characteristic tau cascade consisting of tau hyperphosphorylation, formation of argyrophilic tangles and sarcosyl-insoluble tau complexes. These pathological changes led to the functional impairment characterized by a variety of neurobehavioural symptoms. In the present study we have focused on the behavioural alterations induced by transgenic expression of human truncated tau. Transgenic rats underwent a battery of behavioural tests involving cognitive- and sensorimotor-dependent tasks accompanied with neurological assessment at the age of 4.5, 6 and 9 months. Behavioural examination of these rats showed altered spatial navigation in Morris water maze resulting in less time spent in target quadrant (p<0.05) and fewer crossings over previous platform position (p<0.05) during probe trial. Spontaneous locomotor activity and anxiety in open field was not influenced by transgene expression. However beam walking test revealed that transgenic rats developed progressive sensorimotor disturbances related to the age of tested animals. The disturbances were most pronounced at the age of 9 months (p<0.01). Neurological alterations indicating impaired reflex responses were other added features of behavioural phenotype of this novel transgenic rat. These results allow us to suggest that neurodegeneration, caused by the non-mutated human truncated tau derived from sporadic human AD, result in the neuronal dysfunction consequently leading to the progressive neurobehavioural impairment.

Artificial reproduction of magnetic fields produced by a natural geomagnetic storm increases systolic blood pressure in rats.

PubMed

Martínez-Bretón, J L; Mendoza, B; Miranda-Anaya, M; Durán, P; Flores-Chávez, P L

2016-11-01

The incidence of geomagnetic storms may be associated with changes in circulatory physiology. The way in which the natural variations of the geomagnetic field due to solar activity affects the blood pressure are poorly understood and require further study in controlled experimental designs in animal models. In the present study, we tested whether the systolic arterial pressure (AP) in adult rats is affected by simulated magnetic fields resembling the natural changes of a geomagnetic storm. We exposed adult rats to a linear magnetic profile that simulates the average changes associated to some well-known geomagnetic storm phases: the sudden commencement and principal phase. Magnetic stimulus was provided by a coil inductor and regulated by a microcontroller. The experiments were conducted in the electromagnetically isolated environment of a semi-anechoic chamber. After exposure, AP was determined with a non-invasive method through the pulse on the rat's tail. Animals were used as their own control. Our results indicate that there was no statistically significant effect in AP when the artificial profile was applied, neither in the sudden commencement nor in the principal phases. However, during the experimental period, a natural geomagnetic storm occurred, and we did observe statistically significant AP increase during the sudden commencement phase. Furthermore, when this storm phase was artificially replicated with a non-linear profile, we noticed a 7 to 9 % increase of the rats' AP in relation to a reference value. We suggested that the changes in the geomagnetic field associated with a geomagnetic storm in its first day could produce a measurable and reproducible physiological response in AP.

Geologic Investigations Spurred by Analog Testing at the 7504 Cone-SP Mountain Area of the San Francisco Volcanic Field

NASA Technical Reports Server (NTRS)

Eppler, Dean B.

2015-01-01

The SP Mountain area of the San Francisco Volcanic Field, AZ, has been used as an analog mission development site for NASA since 1998. This area consists of basaltic cinder cones, lava flows and maar craters that have been active since mid-Miocene, with the youngest events occurring within the last 10,000 years. The area has been used because its geologic and topographic resemblance to lunar and Martian terrains provides an ideal venue for testing hardware and science operations practices that might be employed on planetary surfaces, as well as training astronauts in field geology. Analog operations have often led to insights that spurred new scientific investigations. Most recently, an investigation of the 7504 cone was initiated due to perceptions that Apollo-style traverse plans executed during the Desert RATS 2010 mission had characterized the area incorrectly, leading to concerns that the Apollo traverse planning process was scientifically flawed. This investigation revealed a complex history of fissure eruptions of lava and cinders, cinder cone development, a cone-fill-and-spill episode, extensive rheomorphic lava flow initiation and emplacement, and cone sector collapse that led to a final lava flow. This history was not discernible on pre-RATS mission photogeology, although independent analysis of RATS 2010 data and samples develped a "75% complete solution" that validated the pre-RATS mission planning and Apollo traverse planning and execution. The study also pointed out that the development of scientific knowledge with time in a given field area is not linear, but may follow a functional form that rises steeply in the early period of an investigation but flattens out in the later period, asymptotically approaching a theoretical "complete knowledge" point that probably cannot be achieved. This implies that future human missions must be prepared to shift geographic areas of investigation regularly if significant science returns are to be forthcoming.

Geologic Investigations Spurred by Analog Testing at the 7504 Cone-Sp Mountain Area of the San Francisco Volcanic Field

NASA Astrophysics Data System (ADS)

Bleacher, J. E.; Eppler, D. B.; Needham, D. H.; Evans, C. A.; Skinner, J. A.; Feng, W.

2015-12-01

The SP Mountain area of the San Francisco Volcanic Field, AZ, has been used as an analog mission development site for NASA since 1998. This area consists of basaltic cinder cones, lava flows and maar craters that have been active since mid-Miocene, with the youngest events occurring within the last 10,000 years. The area has been used because its geologic and topographic resemblance to lunar and Martian terrains provides an ideal venue for testing hardware and science operations practices that might be employed on planetary surfaces, as well as training astronauts in field geology. Analog operations have often led to insights that spurred new scientific investigations. Most recently, an investigation of the 7504 cone was initiated due to perceptions that Apollo-style traverse plans executed during the Desert RATS 2010 mission had characterized the area incorrectly, leading to concerns that the Apollo traverse planning process was scientifically flawed. This investigation revealed a complex history of fissure eruptions of lava and cinders, cinder cone development, a cone-fill-and-spill episode, extensive rheomorphic lava flow initiation and emplacement, and cone sector collapse that led to a final lava flow. This history was not discernible on pre-RATS mission photogeology, although independent analysis of RATS 2010 data and samples develped a "75% complete solution" that validated the pre-RATS mission planning and Apollo traverse planning and execution. The study also pointed out that the development of scientific knowledge with time in a given field area is not linear, but may follow a functional form that rises steeply in the early period of an investigation but flattens out in the later period, asymptotically approaching a theoretical "complete knowledge" point that probably cannot be achieved. This implies that future human missions must be prepared to shift geographic areas of investigation regularly if significant science returns are to be forthcoming.

Physical exercise prevents motor disorders and striatal oxidative imbalance after cerebral ischemia-reperfusion.

PubMed

Sosa, P M; Schimidt, H L; Altermann, C; Vieira, A S; Cibin, F W S; Carpes, F P; Mello-Carpes, P B

2015-09-01

Stroke is the third most common cause of death worldwide, and most stroke survivors present some functional impairment. We assessed the striatal oxidative balance and motor alterations resulting from stroke in a rat model to investigate the neuroprotective role of physical exercise. Forty male Wistar rats were assigned to 4 groups: a) control, b) ischemia, c) physical exercise, and d) physical exercise and ischemia. Physical exercise was conducted using a treadmill for 8 weeks. Ischemia-reperfusion surgery involved transient bilateral occlusion of the common carotid arteries for 30 min. Neuromotor performance (open-field and rotarod performance tests) and pain sensitivity were evaluated beginning at 24 h after the surgery. Rats were euthanized and the corpora striata was removed for assay of reactive oxygen species, lipoperoxidation activity, and antioxidant markers. Ischemia-reperfusion caused changes in motor activity. The ischemia-induced alterations observed in the open-field test were fully reversed, and those observed in the rotarod test were partially reversed, by physical exercise. Pain sensitivity was similar among all groups. Levels of reactive oxygen species and lipoperoxidation increased after ischemia; physical exercise decreased reactive oxygen species levels. None of the treatments altered the levels of antioxidant markers. In summary, ischemia-reperfusion resulted in motor impairment and altered striatal oxidative balance in this animal model, but those changes were moderated by physical exercise.

Common variations in the pretest environment influence genotypic comparisons in models of anxiety.

PubMed

Izídio, G S; Lopes, D M; Spricigo, L; Ramos, A

2005-10-01

The behavioral characterization of rodent strains in different studies and laboratories can provide unreplicable results even when genotypes are kept constant and environmental control is maximized. In the present study, the influence of common laboratory environmental variables and their interaction with genotype on the results of behavioral tests of anxiety/emotionality were investigated. To this end, the inbred rat strains Lewis (LEW) and spontaneously hypertensive rats (SHR), which are known to differ for numerous emotionality-related behaviors, were tested in the open field (OF), elevated plus maze (EPM) and black/white box (BWB), while three environmental factors were systematically controlled and analyzed: (1) the experimenter handling the animal (familiar or unfamiliar); (2) the position of the home cage (top or bottom shelf of the rack) and (3) the behavioral state of the animal immediately before the test (arousal or rest). Experimenter familiarity did not alter the behavior of rats in the OF. Cage position, on the other hand, influenced the behavior in the OF and BWB, with rats housed in top cages appearing less anxious than those housed in the bottom. In the BWB (but not in the OF), these effects were genotype dependent. Finally, the behavioral state of the animals prior to testing altered the results of the EPM in a strain-dependent manner, with some anxiety-related genotypic differences being found only among rats that were aroused in their home cages. This study showed that common variations in the laboratory environment interact with genotype in behavioral tests of anxiety/emotionality. Recognizing and understanding such variations can help in the design of more effective experiments.

Progestin Concentrations Are Increased following Paced Mating in Midbrain, Hippocampus, Diencephalon, and Cortex of Rats in Behavioral Estrus, but Only in Midbrain of Diestrous Rats

PubMed Central

Frye, Cheryl A.; Rhodes, Madeline E.

2013-01-01

Background The progesterone (P4 ) metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), acts in the midbrain ventral tegmental area (VTA) to modulate the intensity and duration of lordosis. 3α,5α-THP can also have anti-anxiety and anti-stress effects in part through actions in the hippocampus. Separate reports indicate that manipulating 3α,5α-THP levels in the VTA or hippocampus respectively can influence lordosis and affective behavior. 3α,5α-THP levels can also be altered by behavioral experiences, such as mating or swim stress. Whether endogenous levels of 3α,5α-THP modulate and/or are increased in response to affective and/or reproductively-relevant behaviors was investigated. Methods In Experiment 1, rats in behavioral estrus or diestrus were individually tested sequentially in the open field, elevated plus maze, partner preference, social interaction, and paced mating tasks and levels of 17 β-estradiol (E2), P4, dihydroprogesterone (DHP), and 3α,5α-THP in serum, midbrain, hippocampus, diencephalon, and cortex were examined. In Experiments 2 and 3, rats in behavioral estrus or diestrus, were individually tested in the battery indicated above, with, or without, paced mating and tissues were collected immediately after testing for later assessment of endocrine measures. Results In Experiment 1, behavioral estrous, compared to diestrous, rats demonstrated more exploratory, anti-anxiety, social, and reproductive behaviors, and had higher levels of E2 and progestins in serum, midbrain, hippocampus, diencephalon, and cortex. In Experiment 2, in midbrain and hippocampus, levels of 3α,5α-THP and its precursor DHP were increased among rats in behavioral estrus that were mated. In diencephalon, and cortex, DHP levels were increased by mating. In Experiment 3, in midbrain, levels of 3α,5α-THP and its precursor DHP were increased among diestrous rats that were tested in the behavioral battery with mating as compared to those tested in the behavioral battery without mating. Conclusions Increased levels of 3α,5α-THP in behavioral estrus versus diestrous rats are associated with enhanced exploratory, anti-anxiety, social, and reproductive behaviors. Rats in behavioral estrus that are mated have further increases in 3α,5α-THP and/or DHP levels in midbrain, hippocampus, diencephalon, and cortex than do non-mated rats in behavioral estrus, whereas diestrous rats only show 3α,5α-THP increases in midbrain in response to behavioral testing that included mating. PMID:17028418

Different effects of vitamin D hormone treatment on depression-like behavior in the adult ovariectomized female rats.

PubMed

Fedotova, Julia; Dudnichenko, Tatyana; Kruzliak, Peter; Puchavskaya, Zhanna

2016-12-01

Vitamine D (VD) has important functions in the human brain and may play a role in affective-related disorders. VD receptors are expressed in multiple brain regions associated with depressive disorders. The aim of the preclinical study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0mg/kg/day,s.c., once daily, for 14days) on the depression-like behavior and corticosterone levels in the blood samples following ovariectomy in female rats. Cholecalciferol was administered to the ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol (17β-E 2 , 0.5μg/rat,s.c., once daily, for 14days). Depression-like behavior and spontaneous locomotor activity were assessed in the forced swimming test (FST) and the open field test (OFT), respectively. The corticosterone levels in the blood serum before and after FST were measured in all experimental groups. Treatment with cholecalciferol in high dose (5.0mg/kg/day,s.c.) significantly decreased the immobility time of OVX rats in the FST. Co-administration of cholecalciferol in high dose with 17β-E 2 exerted a markedly synergistic antidepressant-like effect in the OVX rats on the same model of depression-like behavior testing. Cholecalciferol in high dose (5.0mg/kg/day,s.c.) administered alone or together with 17β-E 2 significantly enhanced frequency of grooming for the OVX rats in the OFT. Moreover, cholecalciferol in high dose administered alone or together with 17β-E 2 significantly decreased the elevated corticosterone levels in the blood serum of OVX rats following the FST. These results indicate that Cholecalciferol in high dose has a marked antidepressant-like effect in the adult female rats with low levels of estrogen. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A multi-slot surface coil for MRI of dual-rat imaging at 4 T

NASA Astrophysics Data System (ADS)

Solis, S. E.; Wang, R.; Tomasi, D.; Rodriguez, A. O.

2011-06-01

A slotted surface coil inspired by the hole-and-slot cavity magnetron was developed for magnetic resonance imaging of obese rats at 4 T. Full-wave analysis of the magnetic field was carried out at 170 MHz for both the slotted and circular-shaped coils. The noise figure values of two coils were investigated via the numerical calculation of the quality factors. Fat simulated phantoms to mimic overweight rats were included in the analysis with weights ranging from 300 to 900 g. The noise figures were 1.2 dB for the slotted coil and 2.4 dB for the circular coil when loaded with 600 g of simulated phantom. A slotted surface coil with eight circular slots and a circular coil with similar dimensions were built and operated in the transceiver mode, and their performances were experimentally compared. The imaging tests in phantoms demonstrated that the slotted surface coil has a deeper RF-sensitivity and better field uniformity than the single-loop RF-coil. High quality images of two overweight Zucker rats were acquired simultaneously with the slotted surface coil using standard spin-echo pulse sequences. Experimental results showed that the slotted surface coil outperformed the circular coil for imaging considerably overweight rats. Thus, the slotted surface coil can be a good tool for MRI experiments in rats on a human whole-body 4 T scanner.

INFORMATIONAL STRESS AS A DEPRESSION INDUCING FACTOR (EXPERIMENTAL STUDY).

PubMed

Matitaishvili, T; Domianidze, T; Burdjanadze, G; Nadareishvili, D; Khananashvili, M

2017-01-01

Chronic psychogenic stress represents the major initiating agent of psychoneural diseases including depression. We used informational stress model for the purpose of modelling chronic psychogenic stress and depression. The aim of the research was to study behavior of dominant and submissive rats at different stages of informational stress and during depression state. In order to study anxiety and depressive behavior of rats we used "forced swim", "elevated cross maze" and "open-field" tests. The obtained results showed that chronic stressing procedure performed on rats by using the mentioned "informational" stress model led to the development of depression both in dominant and submissive rats. Stressing procedure caused sharp increase of serotonin concentration in hypothalamus of dominant and submissive rats. Under behavioral depression background, sharp increase of serotonin concentration in hypothalamus has been revealed which is caused by the peculiarities of stress model (by uncontrollable stressor. Specifically, by inevitable electric painful irritation).

Depressive-like symptoms in a reserpine-induced model of fibromyalgia in rats.

PubMed

Blasco-Serra, Arantxa; Escrihuela-Vidal, Francesc; González-Soler, Eva M; Martínez-Expósito, Fernando; Blasco-Ausina, M Carmen; Martínez-Bellver, Sergio; Cervera-Ferri, Ana; Teruel-Martí, Vicent; Valverde-Navarro, Alfonso A

2015-11-01

Since the pathogenesis of fibromyalgia is unknown, treatment options are limited, ineffective and in fact based on symptom relief. A recently proposed rat model of fibromyalgia is based on central depletion of monamines caused by reserpine administration. This model showed widespread musculoskeletal pain and depressive-like symptoms, but the methodology used to measure such symptoms has been criticized. Evidence relates the high prevalence of pain and depression in fibromyalgia to common pathogenic pathways, most probably focused on the monoaminergic system. The present study aims at a validation of the reserpine model of fibromyalgia. For this purpose, rats undergoing this model have been tested for depressive-like symptoms with a Novelty-Suppressed Feeding Test adaptation. Animals administered with reserpine and subjected to forced food deprivation performed a smaller number of incursions to the center of the open field, evidenced by a decrease in the per-minute rate of the rats' approaching, smelling or touching the food. They also took more time to eat from the central food than control rats. These NSFT findings suggest the presence of depressive-like disorders in this animal model of fibromyalgia. Copyright © 2015 Elsevier Inc. All rights reserved.

Behavioral sensitization to amphetamine induced by a single i.p. dose of oxotremorine in the rat.

PubMed

Gralewicz, Sławomir

2002-01-01

Earlier experiments have revealed that rats treated with a single dose of chlorphenvinphos (CVP), an irreversible acetylcholinesterase inhibitor, are hyposensitive to amphetamine (AMPH) given three weeks after CVP. Exposure to CVP results in an excess of acetylcholine with subsequent overactivation of the nicotinic as well as muscarinic cholinergic receptors. The purpose of the present experiment was to find out whether a selective activation of muscarinic receptors could induce behavioral hyposensitivity to AMPH. To attain this purpose, male rats were pretreated once with 0.00, 0.135, 0.27 or 0.55 mg/kg of oxotremorine, a muscarinic agonist, and challenged 15 days later with 1.0 mg/kg dose of AMPH. The pre- and postinjection open-field behavior of the rats was tested with the use of a computerized set of activity meters. The testing revealed that in oxotremorine pretreated animals the behavioral response to AMPH, i.e. increase in the ambulatory activity, was not diminished but, to the contrary, it was augmented. This effect was dose-dependent, being most pronounced in rats given the 0.55 mg/kg of oxotremorine. The possible cause of the difference between the effect of CVP and oxotremorine is discussed.

Angiotensin II enhancement during pregnancy influences the emotionality of rat offspring (Rattus norvegicus) in adulthood. Potential use of the Rat Grimace Scale.

PubMed

Senko, Tomas; Olexova, Lucia; Mokosakova, Miroslava; Kršková, Lucia

2017-05-01

One of the systems, which can be prenatally reprogrammed, is the renin-angiotensin-aldosterone system (RAAS). The aim of our experiment was to determine how prenatal activation of RAAS via exposure to elevated levels of angiotensin II (Ang II) influences the rat offspring's emotionality. Pregnant female rats were implanted with osmotic minipumps that continually released Ang II and oval object of the same shape and size was implanted into control dams. The adult offspring (AngII and control groups) were tested in rat grimace scale (RGS), open field test (OF) and elevated plus maze (EPM). Psychological stress increased the RGS score in both groups of animals. AngII animals had significantly lower RGS score (i.e. less negative emotions) in the home cage but higher index of emotional reactivity in RGS. AngII animals had also significantly lower frequency of defecation in OF and had no effect on changes in anxiety-like behaviour. We concluded that maternal activation of RAAS modified some aspect of emotionality of experimental animals and led to an enhanced emotional response to stress situation.

Effects of combined administration of 5-HT1A and/or 5-HT1B receptor antagonists and paroxetine or fluoxetine in the forced swimming test in rats.

PubMed

Tatarczyńska, Ewa; Kłodzińska, Aleksandra; Chojnacka-Wójcik, Ewa

2002-01-01

Clinical data suggest that coadministration of pindolol, a 5-HT1A/5-HT1B/beta-adrenoceptor antagonist, and selective serotonin reuptake inhibitors (SSRIs) may shorten the time of onset of a clinical action and may increase beneficial effects of the therapy of drug-resistant depression. Effects of combined administration of SSRIs and 5-HT receptor ligands are currently evaluated in animal models for the detection of an antidepressant-like activity; however, the obtained results turned out to be inconsistent. The aim of the present study was to investigate effects of a 5-HT1A antagonist (WAY 100635), 5-HT1B antagonists (SB 216641 and GR 127935) or pindolol, given in combination with paroxetine or fluoxetine (SSRIs), in the forced swimming test in rats (Porsolt test). When given alone, paroxetine (10 and 20 mg/kg), fluoxetine (10 and 20 mg/kg), WAY 100635 (0.1 and 1 mg/kg), SB 216641 (2 mg/kg), GR 127935 (10 and 20 mg/kg) and pindolol (4 and 8 mg/kg) did not shorten the immobility time of rats in that test. Interestingly, SB 216641 administered alone at a dose of 4 mg/kg produced a significant reduction of the immobility time in that test. A combination of paroxetine (20 mg/kg) and WAY 100635 or pindolol failed to reveal a significant interaction; on the other hand, when paroxetine was given jointly with SB 216641 (2 mg/kg) or GR 127935 (10 and 20 mg/kg), that combination showed a significant antiimmobility action in the forced swimming test in rats. The active behaviors in that test did not reflect increased general activity because combined administration of both the 5-HT1B antagonists and paroxetine failed to alter the locomotor activity of rats, measured in the open field test. Coadministration of fluoxetine and all the antagonists used did not affect the behavior of rats in the forced swimming test. The obtained results seem to indicate that blockade of 5-HT1B receptors, but not 5-HT1A ones, can facilitate the antidepressant-like effect of paroxetine in the forced swimming test in rats. No interaction was observed between fluoxetine and 5-HT1A/5-HT1B receptor antagonists.

Sex Differences in the Physiological and Behavioral Effects of Chronic Oral Methylphenidate Treatment in Rats

PubMed Central

Robison, Lisa S.; Michaelos, Michalis; Gandhi, Jason; Fricke, Dennis; Miao, Erick; Lam, Chiu-Yim; Mauceri, Anthony; Vitale, Melissa; Lee, Junho; Paeng, Soyeh; Komatsu, David E.; Hadjiargyrou, Michael; Thanos, Panayotis K.

2017-01-01

Methylphenidate (MP) is a psychostimulant prescribed for Attention Deficit Hyperactivity Disorder. Previously, we developed a dual bottle 8-h-limited-access-drinking-paradigm for oral MP treatment of rats that mimics the pharmacokinetic profile of treated patients. This study assessed sex differences in response to this treatment. Male and female Sprague Dawley rats were assigned to one of three treatment groups at 4 weeks of age (n = 12/group): Control (water), low dose (LD) MP, and high dose (HD) MP. Rats drank 4 mg/kg MP (LD) or 30 mg/kg MP (HD) during the first hour, and 10 mg/kg (LD) or 60 mg/kg MP (HD) for the remaining 7 h each day. Throughout 3 months of treatment, rats were monitored for body weight, food intake, and fluid intake; as well as tested for open field behavior, circadian activity, novel object recognition, and social interaction. Chronic MP treated rats exhibited reduced fluid intake during distinct treatment weeks to a greater extent in males, and reduced total fluid intake in males only. HD MP treatment decreased body weight in both sexes, while HD MP increased total food intake in females only, likely to offset energy deficits resulting from MP-induced hyperactivity. LD and HD MP increased locomotor activity in the open field, particularly in females and during later treatment weeks. MP dose-dependently increased activity during the dark cycle of circadian testing in females, while in males hyperactivity was only exhibited by HD rats. HD MP increased center activity to a greater extent in males, while MP increased rearing behavior in females only. MP had no effect on social behavior or novel object recognition in either sex. This study concludes that chronic oral MP treatment at clinically-relevant dosages has significant effects on food intake, body weight, open field behavior, and wake cycle activity. Particularly marked sex differences were apparent for locomotor activity, with females being significantly more sensitive to the hyperactivating effects of the drug. These findings suggest that chronic MP exposure beginning in adolescence can have significant behavioral effects that are both dose- and sex-dependent, and raise concerns regarding the reversibility of these effects post-discontinuation of treatment. PMID:28400722

Natural and synthetic vocalizations of brown rat pups, Rattus norvegicus, enhance attractiveness of bait boxes in laboratory and field experiments.

PubMed

Takács, Stephen; Kowalski, Pawel; Gries, Gerhard

2016-10-01

Rats are often neophobic and thus do not readily enter trap boxes which are mandated in rodent management to help reduce the risk of accidental poisoning or capture of non-target animals. Working with brown rats, Rattus norvegicus, as a model species, our overall objective was to test whether sound cues from pups could be developed as a means to enhance captures of rats in trap boxes. Recording vocalizations from three-day-old pups after removal from their natal nest with both sonic and ultrasonic microphones revealed frequency components in the sonic range (1.8-7.5 kHz) and ultrasonic range (18-24 kHz, 33-55 kHz, 60-96 kHz). In two-choice laboratory bioassays, playback recordings of these vocalizations induced significant phonotactic and arrestment responses by juvenile, subadult and adult female and male rats. The effectiveness of engineered 'synthetic' rat pup sounds was dependent upon their frequency components, sound durations and the sound delivery system. Unlike other speakers, a piezoelectric transducer emitting sound bursts of 21 kHz with a 63-KHz harmonic, and persisting for 20-300 ms, proved highly effective in attracting and arresting adult female rats. In a field experiment, a battery-powered electronic device fitted with a piezoelectric transducer and driven by an algorithm that randomly generated sound cues resembling those recorded from rat pups and varying in fundamental frequency (19-23 kHz), duration (20-300 ms) and intermittent silence (300-5000 ms) significantly enhanced captures of rats in trap boxes baited with a food lure and soiled bedding material of adult female rats. Our study provides proof of concept that rat-specific sound cues or signals can be effectively reproduced and deployed as a means to enhance capture of wild rats. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Supplemental dietary choline during development exerts antidepressant-like effects in adult female rats.

PubMed

Glenn, Melissa J; Adams, Raven S; McClurg, Lauren

2012-03-14

Perinatal choline supplementation in rats is neuroprotective against insults such as fetal alcohol exposure, seizures, and advanced age. In the present study we explored whether dietary choline supplementation may also confer protection from psychological challenges, like stress, and act as a natural buffer against stress-linked psychological disorders, like depression. We previously found that choline supplementation increased adult hippocampal neurogenesis, a function compromised by stress, lowered in depression, and boosted by antidepressants; and increased levels of growth factors linked to depression, like brain-derived neurotrophic factor. Together, these were compelling reasons to study the role of choline in depressed mood. To do this, we treated rats with a choline supplemented diet (5 mg/kg choline chloride in AIN76A) prenatally on embryonic days 10-22, on postnatal days (PD) 25-50, or as adults from PD75 onward. Outside of these treatment periods rats were fed a standard diet (1.1 mg/kg choline chloride in AIN76A); control rats consumed only this diet throughout the study. Starting on PD100 rats' anxiety-like responses to an open field, learning in a water maze, and reactivity to forced swimming were assessed. Rats given choline supplementation during pre- or post-natal development, but not adult-treated rats, were less anxious in the open field and less immobile in the forced swim test than control rats. These effects were not mediated by a learning deficit as all groups performed comparably and well in the water maze. Thus, we offer compelling support for the hypothesis that supplemental dietary choline, at least when given during development, may inoculate an individual against stress and major psychological disorders, like depression. Copyright © 2012 Elsevier B.V. All rights reserved.

Desert RATS 2011: Near-Earth Asteroid Human Exploration Operations

NASA Technical Reports Server (NTRS)

Abercromby, Andrew; Gernhardt, Michael L.; Chappel, Steve

2012-01-01

The Desert Research and Technology Studies (D-RATS) 2011 field test involved the planning and execution of a series of exploration scenarios under operational conditions similar to those that would be expected during a human exploration mission to a near-Earth asteroid (NEA). The focus was on understanding the operations tempo during simulated NEA exploration and the implications of communications latency and limited data bandwidth. Anchoring technologies and sampling techniques were not evaluated due to the immaturity of those technologies and the inability to meaningfully test them at D-RATS. Reduced gravity analogs and simulations are being used to fully evaluate Multi-Mission Space Exploration Vehicle (MMSEV) and extravehicular (EVA) operations and interactions in near-weightlessness at a NEA as part of NASA s integrated analogs program. Hypotheses were tested by planning and performing a series of 1-day simulated exploration excursions comparing test conditions all of which involved a single Deep Space Habitat (DSH) and either zero, one, or two MMSEVs; three or four crewmembers; one of two different communications bandwidths; and a 100-second roundtrip communications latency between the field site and Houston. Excursions were executed at the Black Point Lava Flow test site with a Mission Control Center and Science Support Room at Johnson Space Center (JSC) being operated with 100-second roundtrip communication latency to the field. Crews were composed of astronauts and professional field geologists and teams of Mission Operations, Science, and Education & Public Outreach (EPO) experts also supported the mission simulations each day. Data were collected separately from the Crew, Mission Operations, Science, and EPO teams to assess the test conditions from multiple perspectives. For the operations tested, data indicates practically significant benefits may be realized by including at least one MMSEV and by including 4 versus 3 crewmembers in the NEA exploration architecture as measured by increased Scientific Data Quality, EVA Exploration Time, Capability Assessment Ratings, and Overall Acceptability ratings by Crew, Mission Operations, Science, and Education & Public Outreach teams. A combination of text and voice was used to effectively communicate over the 100-second roundtrip communications latency and increased communication bandwidth yielded a small but practically significant improvement in Overall Acceptability as rated by the Science team, although the impact of bandwidth on scientific strategic planning was not assessed. No effect of increased bandwidth was observed with respect to Crew, Mission Operations, or EPO team ratings of Overall Acceptability.

Effects of prenatal exposure to a 900 MHz electromagnetic field on 60-day-old rat testis and epididymal sperm quality.

PubMed

Odacı, E; Hancı, H; Yuluğ, E; Türedi, S; Aliyazıcıoğlu, Y; Kaya, H; Çolakoğlu, S

2016-01-01

We investigated the effects of exposure in utero to a 900 megahertz (MHz) electromagnetic field (EMF) on 60-day-old rat testis and epididymis. Pregnant rats were divided into control (CG; no treatment) and EMF (EMFG) groups. The EMFG was exposed to 900 MHz EMF for 1 h each day during days 13 - 21 of pregnancy. Newborn rats were either newborn CG (NCG) or newborn EMF groups (NEMFG). On postnatal day 60, a testis and epididymis were removed from each animal. Epididymal semen quality, and lipid and DNA oxidation levels, apoptotic index and histopathological damage to the testis were compared. We found a higher apoptotic index, greater DNA oxidation levels and lower sperm motility and vitality in the NEMFG compared to controls. Immature germ cells in the seminiferous tubule lumen, and altered seminiferous tubule epithelium and seminiferous tubule structure also were observed in hematoxylin and eosin stained sections of NEMFG testis. Nuclear changes that indicated apoptosis were identified in TUNEL stained sections and large numbers of apoptotic cells were observed in most of the seminiferous tubule epithelium in the NEMFG. Sixty-day-old rat testes exposed to 900 MHz EMF exhibited altered sperm quality and biochemical characteristics.

Suppression of Neuroinflammatory and Apoptotic Signaling Cascade by Curcumin Alone and in Combination with Piperine in Rat Model of Olfactory Bulbectomy Induced Depression

PubMed Central

Rinwa, Puneet; Kumar, Anil; Garg, Sukant

2013-01-01

Objectives Bilateral destruction of the olfactory bulbs is known to cause behavioral changes analogous to symptoms of depression. Curcumin, a traditional Indian spice is currently being investigated in different psychiatric problems including depression. Dietary phytochemicals are currently used as an adjuvant therapy to accelerate their therapeutic efficacy. Therefore, the present study is an attempt to elucidate the neuroprotective mechanism of curcumin and its co-administration with piperine against olfactory bulbectomy induced depression in rats. Methods Rats undergone olfactory bulbs ablations were analyzed after post-surgical rehabilitation period of 2 weeks. Animals were then treated with different doses of curcumin (100, 200 and 400 mg/kg; p.o.), piperine (20 mg/kg; p.o.) and their combination daily for another 2 weeks. Imipramine (10 mg/kg; i.p.) served as a standard control. Various behavioral tests like forced swim test (FST), open field behaviour and sucrose preference test (SPT) were performed, followed by estimation of biochemical, mitochondrial, molecular and histopathological parameters in rat brain. Results Ablation of olfactory bulbs caused depression-like symptoms as evidenced by increased immobility time in FST, hyperactivity in open field arena, and anhedonic like response in SPT along with alterations in mitochondrial enzyme complexes, increased serum corticosterone levels and oxidative damage. These deficits were integrated with increased inflammatory cytokines (TNF-α) and apoptotic factor (caspase-3) levels along with a marked reduction in neurogenesis factor (BDNF) in the brain of olfactory bulbectomized (OBX) rats. Curcumin treatment significantly and dose-dependently restored all these behavioral, biochemical, mitochondrial, molecular and histopathological alterations associated with OBX induced depression. Further, co-administration of piperine with curcumin significantly potentiated their neuroprotective effects as compared to their effects alone. Conclusions The present study highlights that curcumin along with piperine exhibits neuroprotection against olfactory bulbectomy induced depression possibly by modulating oxidative-nitrosative stress induced neuroinflammation and apoptosis. PMID:23613781

Structural and functional effects of social isolation on the hippocampus of rats with traumatic brain injury.

PubMed

Khodaie, Babak; Lotfinia, Ahmad Ali; Ahmadi, Milad; Lotfinia, Mahmoud; Jafarian, Maryam; Karimzadeh, Fariba; Coulon, Philippe; Gorji, Ali

2015-02-01

Social isolation has significant long-term psychological and physiological consequences. Both social isolation and traumatic brain injury (TBI) alter normal brain function and structure. However, the influence of social isolation on recovery from TBI is unclear. This study aims to evaluate if social isolation exacerbates the anatomical and functional deficits after TBI in young rats. Juvenile male rats were divided into four groups; sham operated control with social contacts, sham control with social isolation, TBI with social contacts, and TBI with social isolation. During four weeks after brain injury in juvenile rats, we evaluated the animal behaviors by T-maze and open-field tests, recorded brain activity with electrocorticograms and assessed structural changes by histological procedures in the hippocampal dentate gyrus, CA1, and CA3 areas. Our findings revealed significant memory impairments and hyperactivity conditions in rats with TBI and social isolation compared to the other groups. Histological assessments showed an increase of the mean number of dark neurons, apoptotic cells, and caspase-3 positive cells in all tested areas of the hippocampus in TBI rats with and without social isolation compared to sham rats. Furthermore, social isolation significantly increased the number of dark cells, apoptotic neurons, and caspase-3 positive cells in the hippocampal CA3 region in rats with TBI. This study indicates the harmful effect of social isolation on anatomical and functional deficits induced by TBI in juvenile rats. Prevention of social isolation may improve the outcome of TBI. Copyright © 2014 Elsevier B.V. All rights reserved.

Sex differences and sex hormones in anxiety-like behavior of aging rats.

PubMed

Domonkos, Emese; Borbélyová, Veronika; Csongová, Melinda; Bosý, Martin; Kačmárová, Mária; Ostatníková, Daniela; Hodosy, Július; Celec, Peter

2017-07-01

Sex differences in the prevalence of affective disorders might be attributable to different sex hormone milieu. The effects of short-term sex hormone deficiency on behavior, especially on anxiety have been studied in numerous animal experiments, mainly on young adult rats and mice. However, sex differences in aged animals and the effects of long-term hypogonadism are understudied. The aim of our study was to analyze sex differences in anxiety-like behavior in aged rats and to prove whether they can be attributed to endogenous sex hormone production in males. A battery of tests was performed to assess anxiety-like behavior in aged female, male and gonadectomized male rats castrated before puberty. In addition, the aged gonadectomized male rats were treated with a single injection of estradiol or testosterone or supplemented with estradiol for two-weeks. Female rats displayed a less anxious behavior than male rats in most of the conducted behavioral tests except the light-dark box. Long-term androgen deficiency decreased the sex difference in anxiety either partially (open field, PhenoTyper cage) or completely (elevated plus maze). Neither single injection of sex hormones, nor two-week supplementation of estradiol in gonadectomized aged male rats significantly affected their anxiety-like behavior in the elevated plus maze. In conclusion, our results confirm sex differences in anxiety in aged rats likely mediated by endogenous testosterone production in males. Whether long-term supplementation with exogenous sex hormones could affect anxiety-like behavior in elderly individuals remains to be elucidated. Copyright © 2017 Elsevier Inc. All rights reserved.

Long term treadmill exercise performed to chronic social isolated rats regulate anxiety behavior without improving learning.

PubMed

Cevik, Ozge Selin; Sahin, Leyla; Tamer, Lulufer

2018-05-01

The type and duration of exposure to stress is an important influence on emotional and cognitive functions. Learning is the adaptive response of the central nervous system that occurs in hippocampus which affects from environmental factors like exercise. In this study, we investigated effects of long term treadmill exercise on learning and behavior on chronic social isolated rat. Male Wistar rats (n = 32) randomly assigned into four groups: control, exercised, social isolation, social isolation + exercise during postnatal days (PNDs) 21-34. Social isolation protocol was applied during 14 days by placing rat in a cage one by one. Rats were exercised during 5 days, days were chosen randomly for overall 4 weeks (20, 30, 50, 60 min respectively). Finally, learning performance was evaluated by Morris water maze (MWM). Anxiety behavior was evaluated by Open field and elevated plus maze test. At the end of learning and behavior tests, the rats were decapitated to collect blood samples via intracardiac puncture and corticosterone analysis was performed with ELISA method. Animal weights and water consumption did not change significantly but food intake differed among groups. Corticosterone level did not change between groups. The frequency of entering to the target quadrant increased in exercised rat significantly. However, there was no difference in learning and memory in rats. Treadmill exercise reduced anxiety behavior significantly. Taken together these findings may point out that, long term treadmill exercise did not change learning and memory but reduced anxiety level of rat without changing corticosterone level. Copyright © 2018 Elsevier Inc. All rights reserved.

Maternal Deprivation of Lewis Rat Pups Increases the Severity of Experi-mental Periodontitis in Adulthood

PubMed Central

Breivik, Torbjørn; Gundersen, Yngvar; Murison, Robert; Turner, Jonathan D; Muller, Claude P; Gjermo, Per; Opstad, Kristian

2015-01-01

Background and Objective: Early life adverse events may influence susceptibility/resistance to chronic inflammatory diseases later in life by permanently dysregulating brain-controlled immune-regulatory systems. We have investigated the impact of infant-mother separation during early postnatal life on the severity of experimental periodontitis, as well as systemic stress and immune responses, in adulthood. Material and Methods: Pups of periodontitis resistant Lewis rats were separated from their mothers for 3 h daily during postnatal days 2-14 (termed maternal deprivation; MD), separated for 15 min daily during the same time period (termed handling; HD), or left undisturbed. As adults, their behaviour was tested in a novel stressful situation, and ligature-induced periodontitis applied for 21 days. Two h before sacrifice all rats were exposed to a gram-negative bacterial lipopolysaccharide (LPS) challenge to induce a robust immune and stress response. Results: Compared to undisturbed controls, MD rats developed significantly more periodontal bone loss as adults, whereas HD rats showed a tendency to less disease. MD and HD rats exhibited depression-like behaviour in a novel open field test, while MD rats showed higher glucocorticoid receptor (Gr) expression in the hippocampus, and HD rats had altered methylation of genes involved in the expression of hippocampal Gr. LPS provoked a significantly lower increase in circulating levels of the cytokine TGF-1β in MD and HD rats, but there were no significant differences in levels of the stress hormone corticosterone. Conclusion: Stressful environmental exposures in very early life may alter immune responses in a manner that influences susceptibility/resistance to periodontitis. PMID:25713634

Maternal Deprivation of Lewis Rat Pups Increases the Severity of Experi-mental Periodontitis in Adulthood.

PubMed

Breivik, Torbjørn; Gundersen, Yngvar; Murison, Robert; Turner, Jonathan D; Muller, Claude P; Gjermo, Per; Opstad, Kristian

2015-01-01

Early life adverse events may influence susceptibility/resistance to chronic inflammatory diseases later in life by permanently dysregulating brain-controlled immune-regulatory systems. We have investigated the impact of infant-mother separation during early postnatal life on the severity of experimental periodontitis, as well as systemic stress and immune responses, in adulthood. Pups of periodontitis resistant Lewis rats were separated from their mothers for 3 h daily during postnatal days 2-14 (termed maternal deprivation; MD), separated for 15 min daily during the same time period (termed handling; HD), or left undisturbed. As adults, their behaviour was tested in a novel stressful situation, and ligature-induced periodontitis applied for 21 days. Two h before sacrifice all rats were exposed to a gram-negative bacterial lipopolysaccharide (LPS) challenge to induce a robust immune and stress response. Compared to undisturbed controls, MD rats developed significantly more periodontal bone loss as adults, whereas HD rats showed a tendency to less disease. MD and HD rats exhibited depression-like behaviour in a novel open field test, while MD rats showed higher glucocorticoid receptor (Gr) expression in the hippocampus, and HD rats had altered methylation of genes involved in the expression of hippocampal Gr. LPS provoked a significantly lower increase in circulating levels of the cytokine TGF-1β in MD and HD rats, but there were no significant differences in levels of the stress hormone corticosterone. Stressful environmental exposures in very early life may alter immune responses in a manner that influences susceptibility/resistance to periodontitis.

Duration-dependence of the effect of treadmill exercise on hyperactivity in attention deficit hyperactivity disorder rats.

PubMed

Ji, Eun-Sang; Kim, Chang-Ju; Park, Jun Heon; Bahn, Geon Ho

2014-04-01

Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder, and its symptoms are hyperactivity and deficits in learning and memory. Physical exercise increases dopamine synthesis and neuronal activity in various brain regions. In the present study, we investigate the duration-dependence of the treadmill exercise on hyperactivity in relation with dopamine expression in ADHD. Spontaneously hypertensive rats were used for the ADHD rats and Wistar-Kyoto rats were used for the control rats. The rats in the exercise groups were forced to run on a treadmill for 10 min, 30 min, and 60 min once daily for 28 consecutive days. For this experiment, open field test and immunohistochemistry for tyrosine hydroxylase were conducted. The present results revealed that ADHD rats showed hyperactivity, and tyrosine hydroxylase expression in the striatum and substantia nigra were decreased in ADHD rats. Treadmill exercise alleviated hyperactivity and also increased TH expression in ADHD rats. Treadmill exercise for 30 min per day showed most potent suppressing effect on hyperactivity, and this dose of treadmill exercise also most potently inhibited tyrosine hydroxylase expression. The present study suggests that treadmill exercise for 30 min once a day is the most effective therapeutic intervention for ADHD patients.

Neural hyperactivity in the amygdala induced by chronic treatment of rats with analgesics may elucidate the mechanisms underlying psychiatric comorbidities associated with medication-overuse headache.

PubMed

Wanasuntronwong, Aree; Jansri, Ukkrit; Srikiatkhachorn, Anan

2017-01-03

Patients with medication-overuse headache suffer not only from chronic headache, but often from psychiatric comorbidities, such as anxiety and depression. The mechanisms underlying these comorbidities are unclear, but the amygdala is likely to be involved in their pathogenesis. To investigate the mechanisms underlying the comorbidities we used elevated plus maze and open field tests to assess anxiety-like behavior in rats chronically treated with analgesics. We measured the electrical properties of neurons in the amygdala, and examined the cortical spreading depression (CSD)-evoked expression of Fos in the trigeminal nucleus caudalis (TNC) and amygdala of rats chronically treated with analgesics. CSD, an analog of aura, evokes Fos expression in the TNC of rodents suggesting trigeminal nociception, considered to be a model of migraine. Increased anxiety-like behavior was seen both in elevated plus maze and open field tests in a model of medication overuse produced in male rats by chronic treatment with aspirin or acetaminophen. The time spent in the open arms of the maze by aspirin- or acetaminophen-treated rats (53 ± 36.1 and 37 ± 29.5 s, respectively) was significantly shorter than that spent by saline-treated vehicle control rats (138 ± 22.6 s, P < 0.001). Chronic treatment with the analgesics increased the excitability of neurons in the central nucleus of the amygdala as indicated by their more negative threshold for action potential generation (-54.6 ± 5.01 mV for aspirin-treated, -55.2 ± 0.97 mV for acetaminophen-treated, and -31.50 ± 5.34 mV for saline-treated rats, P < 0.001). Chronic treatment with analgesics increased the CSD-evoked expression of Fos in the TNC and amygdala [18 ± 10.2 Fos-immunoreactive (IR) neurons per slide in the amygdala of rats treated with aspirin, 11 ± 5.4 IR neurons per slide in rats treated with acetaminophen, and 4 ± 3.7 IR neurons per slide in saline-treated control rats, P < 0.001]. Chronic treatment with analgesics can increase the excitability of neurons in the amygdala, which could underlie the anxiety seen in patients with medication-overuse headache.

[Effect of selenium deficiency on the F344 inbred line offspring rats' neuro-behavior, ability of learning and memory].

PubMed

Hong, Liang-Li; Tian, Dong-Ping; Su, Min; Shen, Xiu-Na; Gao, Yuxia

2006-01-01

To establish the selenium (Se) deficient animal model on F344 inbred line rats and observe the effects of a long-term Se-deficiency on the offspring's neuro-behavior, abilities of learning and memory. Feeding F344 inbred line rats on Se-deficient diet to establish Se-deficient animal model. For the offspring, the body weight, physiological indexes nervous reflections for growth and development were monitored during the early postnatal period. The Se-deficient diet contained less than 0.01 mg/kg and the glutathione peroxidase (GSH-Px) activity in blood of the Se-deficient group rats is lower than the Se-normal group after feeding on Se-deficient diet for 4 weeks. For the offspring, the birth weight and the body weight of Se-deficient group were obviously lower than the Se-normal group before weaning. Se-deficient offspring rats differed from Se-normal controls in lower scores in surface righting reflex (RR) test at postnatal 4th day after delivery, cliff avoidance test at postnatal 7th day and auditory acuity trial at postnatal 10th day respectively. But these differences disappear after a few days in the same tests. In addition, no significant differences between two groups in suspending test and walking ability test at postnatal 12th and 14th day. In open field test, Se-deficient male offspring stayed less time in the middle grid and moved less. In Morris water maze test, the Se-deficient offspring spent more time to find the hidden platform at the 6th and 9th training tests in the place navigation trial. Furthermore, the Se-deficient group spent less time in target quadrant when giving the spatial probe trial. A Se-deficient animal model have been established on F344 inbred line rats successfully. A long-term Se deficiency could retard the development of the offspring in uterus and after delivery. Se deficiency also decreased the offspring's abilities of spatial learning and memory in Morris water maze test and resulted in the male offspring's nervousness to new stimulant.

Behavioral and neurochemical effects of repeated MDMA administration during late adolescence in the rat

PubMed Central

Cox, Brittney M.; Shah, Mrudang M.; Cichon, Teri; Tancer, Manuel E.; Galloway, Matthew P.; Thomas, David M.; Perrine, Shane A.

2015-01-01

Adolescents and young adults disproportionately abuse 3,4-methylenedioxymethamphetamine (MDMA; ‘Ecstasy’); however, since most MDMA research has concentrated on adults, the effects of MDMA on the developing brain remain obscure. Therefore, we evaluated place conditioning to MDMA (or saline) during late adolescence and assessed anxiety-like behavior and monoamine levels during abstinence. Rats were conditioned to associate 5 or 10 mg/kg MDMA or saline with contextual cues over 4 twice-daily sessions. Five days after conditioning, anxiety-like behavior was examined with the open field test and brain tissue was collected to assess serotonin (5-hydroxytryptamine, 5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the dorsal raphe, amygdala, and hippocampus by high-pressure liquid chromatography (HPLC). In a separate group of rats, anxiety-like and avoidant behaviors were measured using the light–dark box test under similar experimental conditions. MDMA conditioning caused a place aversion at 10, but not at 5, mg/kg, as well as increased anxiety-like behavior in the open field and avoidant behavior in light–dark box test at the same dose. Additionally, 10 mg/kg MDMA decreased 5-HT in the dorsal raphe, increased 5-HT and 5-HIAA in the amygdala, and did not alter levels in the hippocampus. Overall, we show that repeated high (10 mg/kg), but not low (5 mg/kg), dose MDMA during late adolescence in rats increases anxiety-like and avoidant behaviors, accompanied by region-specific alterations in 5-HT levels during abstinence. These results suggest that MDMA causes a region-specific dysregulation of the serotonin system during adolescence that may contribute to maladaptive behavior. PMID:24121061

Testing electromagnetic fields for potential carcinogenic activity: a critical review of animal models.

PubMed Central

McCann, J; Kavet, R; Rafferty, C N

1997-01-01

In order to assess the potential of electromagnetic fields (EMF) to influence the process of carcinogenesis, it will be necessary to supplement epidemiological studies with controlled laboratory studies in animals. There are now a number of suitable assays available that focus on different histopathological forms of cancer and on different stages of carcinogenesis--induction, promotion, progression. In this review we discuss eight major systems in the context of this generalized carcinogenesis paradigm. Our aim is to bring together what is currently known about the biology of carcinogenesis in these systems in order to provide a context for evaluating EMF results as they become available. We also critically discuss EMF test results that have so far been obtained in the animal models reviewed. Most of the 19 completed studies identified were negative. However, suggestive positive results were reported in three promotion assays (in rat mammary gland, in rat liver, and in mouse skin), and in one multigeneration study in mice. Results in the rat liver assay and in the multigeneration study have only been reported in abstract form and cannot be adequately evaluated. Positive results reported in both the rat mammary gland and the mouse skin systems are of weak statistical significance and have not been independently replicated. However, it may be of interest that effects in both systems appear primarily to involve the progression stage of carcinogenesis. We suggest that more definitive conclusions as to the carcinogenic potential of EMF may require expanded test protocols that reinforce traditional carcinogenesis end points with biochemical or other parameters reflective of biological processes known to be associated with carcinogenesis in the different systems. PMID:9114279

Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat.

PubMed

Pic-Taylor, Aline; da Motta, Luciana Gueiros; de Morais, Juliana Alves; Junior, Willian Melo; Santos, Alana de Fátima Andrade; Campos, Leandro Ambrósio; Mortari, Marcia Renata; von Zuben, Marcus Vinicius; Caldas, Eloisa Dutra

2015-09-01

Ayahuasca, a psychoactive beverage used by indigenous and religious groups, is generally prepared by the coction of Psychotria viridis and Banisteriopsis caapi plants containing N,N-dimethyltryptamine (DMT) and β-carboline alkaloids, respectively. To investigate the acute toxicity of ayahuasca, the infusion was administered by gavage to female Wistar rats at doses of 30X and 50X the dose taken during a religious ritual, and the animals observed for 14 days. Behavioural functions were investigated one hour after dosing at 15X and 30X using the open field, elevated plus maze, and forced swimming tests. Neuronal activation (c-fos marked neurons) and toxicity (Fluoro-Jade B and Nissl/Cresyl staining) were investigated in the dorsal raphe nuclei (DRN), amygdaloid nucleus, and hippocampal formation brain areas of rats treated with a 30X ayahuasca dose. The actual lethal oral dose in female Wistar rats could not be determined in this study, but was shown to be higher than the 50X (which corresponds to 15.1mg/kg bw DMT). The ayahuasca and fluoxetine treated groups showed a significant decrease in locomotion in the open field and elevated plus-maze tests compared to controls. In the forced swimming test, ayahuasca treated animals swam more than controls, a behaviour that was not significant in the fluoxetine group. Treated animals showed higher neuronal activation in all brain areas involved in serotoninergic neurotransmission. Although this led to some brain injury, no permanent damage was detected. These results suggest that ayahuasca has antidepressant properties in Wistar female at high doses, an effect that should be further investigated. Copyright © 2015 Elsevier B.V. All rights reserved.

Adolescent exposure to Bisphenol-A increases anxiety and sucrose preference but impairs spatial memory in rats independent of sex.

PubMed

Diaz Weinstein, Samantha; Villafane, Joseph J; Juliano, Nicole; Bowman, Rachel E

2013-09-05

The endocrine disruptor Bisphenol-A (BPA) has been shown to modulate estrogenic, androgenic, and anti-androgenic effects. The effects of BPA exposure during early organizational periods of development have been well documented. The current study focuses on the effects of short term, low-dose BPA exposure on anxiety, spatial memory and sucrose preference in adolescent rats. Seven week old Sprague Dawley rats (n=18 male, n=18 female) received daily subcutaneous injections (40 µg/kg body weight) of BPA or vehicle for 12 days. Starting on day 6 of injections, subjects were tested on the elevated plus maze which provides a measure of anxiety, the open field test which provides a measure of anxiety and locomotor activity, and object placement, a measure of spatial memory. On the twelfth day of BPA administration, sucrose preference was tested using a standard two-bottle choice (tap versus sucrose solution). All rats gained weight during the study; there was a main effect of sex, but not BPA treatment on body weight. The results indicate that BPA exposure, regardless of sex, increased anxiety on both the elevated plus maze and open field. Spatial memory was impaired on the object recognition task with BPA animals spending significant less time with the object in the novel location than controls. Finally, a significant increase in sucrose consumption for both male and female subjects exposed to BPA was observed. The current data shows that short term BPA exposure, below the current reference safe daily limit of 50 µg/kg day set by the United States Environmental Protection Agency, during adolescent development increases anxiety, impairs spatial memory, and increases sucrose consumption independent of sex. Copyright © 2013 Elsevier B.V. All rights reserved.

Adolescent fluoxetine exposure produces enduring, sex-specific alterations of visual discrimination and attention in rats.

PubMed

LaRoche, Ronee B; Morgan, Russell E

2007-01-01

Over the past two decades the use of selective serotonin reuptake inhibitors (SSRIs) to treat behavioral disorders in children has grown rapidly, despite little evidence regarding the safety and efficacy of these drugs for use in children. Utilizing a rat model, this study investigated whether post-weaning exposure to a prototype SSRI, fluoxetine (FLX), influenced performance on visual tasks designed to measure discrimination learning, sustained attention, inhibitory control, and reaction time. Additionally, sex differences in response to varying doses of fluoxetine were examined. In Experiment 1, female rats were administered (P.O.) fluoxetine (10 mg/kg ) or vehicle (apple juice) from PND 25 thru PND 49. After a 14 day washout period, subjects were trained to perform a simultaneous visual discrimination task. Subjects were then tested for 20 sessions on a visual attention task that consisted of varied stimulus delays (0, 3, 6, or 9 s) and cue durations (200, 400, or 700 ms). In Experiment 2, both male and female Long-Evans rats (24 F, 24 M) were administered fluoxetine (0, 5, 10, or 15 mg/kg) then tested in the same visual tasks used in Experiment 1, with the addition of open-field and elevated plus-maze testing. Few FLX-related differences were seen in the visual discrimination, open field, or plus-maze tasks. However, results from the visual attention task indicated a dose-dependent reduction in the performance of fluoxetine-treated males, whereas fluoxetine-treated females tended to improve over baseline. These findings indicate that enduring, behaviorally-relevant alterations of the CNS can occur following pharmacological manipulation of the serotonin system during postnatal development.

Behavioral and neurochemical effects of repeated MDMA administration during late adolescence in the rat.

PubMed

Cox, Brittney M; Shah, Mrudang M; Cichon, Teri; Tancer, Manuel E; Galloway, Matthew P; Thomas, David M; Perrine, Shane A

2014-01-03

Adolescents and young adults disproportionately abuse 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy'); however, since most MDMA research has concentrated on adults, the effects of MDMA on the developing brain remain obscure. Therefore, we evaluated place conditioning to MDMA (or saline) during late adolescence and assessed anxiety-like behavior and monoamine levels during abstinence. Rats were conditioned to associate 5 or 10mg/kg MDMA or saline with contextual cues over 4 twice-daily sessions. Five days after conditioning, anxiety-like behavior was examined with the open field test and brain tissue was collected to assess serotonin (5-hydroxytryptamine, 5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the dorsal raphe, amygdala, and hippocampus by high-pressure liquid chromatography (HPLC). In a separate group of rats, anxiety-like and avoidant behaviors were measured using the light-dark box test under similar experimental conditions. MDMA conditioning caused a place aversion at 10, but not at 5, mg/kg, as well as increased anxiety-like behavior in the open field and avoidant behavior in light-dark box test at the same dose. Additionally, 10mg/kg MDMA decreased 5-HT in the dorsal raphe, increased 5-HT and 5-HIAA in the amygdala, and did not alter levels in the hippocampus. Overall, we show that repeated high (10mg/kg), but not low (5mg/kg), dose MDMA during late adolescence in rats increases anxiety-like and avoidant behaviors, accompanied by region-specific alterations in 5-HT levels during abstinence. These results suggest that MDMA causes a region-specific dysregulation of the serotonin system during adolescence that may contribute to maladaptive behavior. © 2013.

Treatment with tianeptine induces antidepressive-like effects and alters the neurotrophin levels, mitochondrial respiratory chain and cycle Krebs enzymes in the brain of maternally deprived adult rats.

PubMed

Della, Franciela P; Abelaira, Helena M; Réus, Gislaine Z; Santos, Maria Augusta B dos; Tomaz, Débora B; Antunes, Altamir R; Scaini, Giselli; Morais, Meline O S; Streck, Emilio L; Quevedo, João

2013-03-01

Maternally deprived rats were treated with tianeptine (15 mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed using the forced swimming and open field tests. The BDNF, NGF and energy metabolism were assessed in the rat brain. Deprived rats increased the immobility time, but tianeptine reversed this effect and increased the swimming time; the BDNF levels were decreased in the amygdala of the deprived rats treated with saline and the BDNF levels were decreased in the nucleus accumbens within all groups; the NGF was found to have decreased in the hippocampus, amygdala and nucleus accumbens of the deprived rats; citrate synthase was increased in the hippocampus of non-deprived rats treated with tianeptine and the creatine kinase was decreased in the hippocampus and amygdala of the deprived rats; the mitochondrial complex I and II-III were inhibited, and tianeptine increased the mitochondrial complex II and IV in the hippocampus of the non-deprived rats; the succinate dehydrogenase was increased in the hippocampus of non-deprived rats treated with tianeptine. So, tianeptine showed antidepressant effects conducted on maternally deprived rats, and this can be attributed to its action on the neurochemical pathways related to depression.

[Morphometry of giant multipolar neurons of the brain stem reticular formation in rats on board the Kosmos-1667 biosatellite].

PubMed

Belichenko, P V; Leontovich, T A

1989-05-01

Giant multipolar neurons of nucleus reticularis gigantocellularis of rats which had been kept on board the biosatellite "Kosmos-1667" were morphometrically studied. There was a trend towards the increase in the cellular surface, the maximum diameter of dendritic field, the volume of the whole dendritic territory in the test group ad in the control experimental group kept on the earth. A reliable decrease in dendritic mass oriented to nucleus vestibularis and an increase in dendritic mass oriented to the midline were also found in test group, as compared to 3 control groups. Our data were discussed in the light of nervous tissue plasticity in adult mammals.

[Effect of space flight factors simulated in ground-based experiments on the behavior, discriminant learning, and exchange of monoamines in different brain structures of rats].

PubMed

Shtemberg, A S; Lebedeva-Georgievskaia, K V; Matveeva, M I; Kudrin, V S; Narkevich, V B; Klodt, P M; Bazian, A S

2014-01-01

Experimental treatment (long-term fractionated γ-irradiation, antiorthostatic hypodynamia, and the combination of these factors) simulating the effect of space flight in ground-based experiments rapidly restored the motor and orienting-investigative activity of animals (rats) in "open-field" tests. The study of the dynamics of discriminant learning of rats of experimental groups did not show significant differences from the control animals. It was found that the minor effect of these factors on the cognitive performance of animals correlated with slight changes in the concentration ofmonoamines in the brain structures responsible for the cognitive, emotional, and motivational functions.

Structural and ultrastructural study of rat testes influenced by electromagnetic radiation.

PubMed

Almášiová, Viera; Holovská, Katarína; Cigánková, Viera; Račeková, Enikö; Fabianová, Kamila; Martončíková, Marcela

2014-01-01

This study was conducted to investigate the influence of whole-body electromagnetic radiation (EMR) on testicular parenchyma of Wistar rats. Sexually mature rats were subjected to pulsed electromagnetic field at frequency of 2.45 GHz and mean power density 2.8 mW/cm(2) by 3-h daily applications for 3 wk. Tissue samples were obtained 3 h after the last irradiation and processed by histological techniques for light and transmission electron microscopy. Testes showed apparent degenerative changes of seminiferous epithelium. The seminiferous tubules were mostly irregular in shape, and seminiferous epithelium contained a number of empty spaces of different size. Subsequently, groups of sloughed epithelial cells were often found inside the lumina of tubules. Except for relatively unchanged Sertoli cells, some locations of basal compartment of seminiferous epithelium contained shriveled Sertoli cells with dark cytoplasm. These areas showed degenerative features including necrotizing and shriveled spermatogonia surrounded by empty irregular spaces, and undulating basement membrane. The intertubular spaces were enlarged but interstitial Leydig cells did not show any marked morphological changes. Evidence demonstrates the adverse effects of EMR on testicular parenchyma in rats.

Early application of tail nerve electrical stimulation-induced walking training promotes locomotor recovery in rats with spinal cord injury.

PubMed

Zhang, S-X; Huang, F; Gates, M; Shen, X; Holmberg, E G

2016-11-01

This is a randomized controlled prospective trial with two parallel groups. The objective of this study was to determine whether early application of tail nerve electrical stimulation (TANES)-induced walking training can improve the locomotor function. This study was conducted in SCS Research Center in Colorado, USA. A contusion injury to spinal cord T10 was produced using the New York University impactor device with a 25 -mm height setting in female, adult Long-Evans rats. Injured rats were randomly divided into two groups (n=12 per group). One group was subjected to TANES-induced walking training 2 weeks post injury, and the other group, as control, received no TANES-induced walking training. Restorations of behavior and conduction were assessed using the Basso, Beattie and Bresnahan open-field rating scale, horizontal ladder rung walking test and electrophysiological test (Hoffmann reflex). Early application of TANES-induced walking training significantly improved the recovery of locomotor function and benefited the restoration of Hoffmann reflex. TANES-induced walking training is a useful method to promote locomotor recovery in rats with spinal cord injury.

(-)Epigallocatechin-3-gallate prevents the reserpine-induced impairment of short-term social memory in rats.

PubMed

Tseng, Hsiang-Chien; Wang, Mao-Hsien; Soung, Hung-Sheng; Chang, Yi; Chang, Kuo-Chi

2015-12-01

Reserpine has been confirmed to induce cognitive dysfunction and increase brain neural oxidative stress. Green tea catechins, particularly (-)epigallocatechin-3-gallate (EGCG), have strong antioxidative properties and can protect against numerous oxidative damages. In this study, we examined the possible protective effects of EGCG on reserpine-induced impairment of short-term memory in rats. Reserpine (1 mg/kg, intraperitoneal)-induced memory impairment was assessed using the social recognition task method; locomotor activity and the olfactory discrimination ability were not altered as measured by an open-field test and an olfactory discrimination test, respectively. EGCG treatment (100 and 300 mg/kg, intraperitoneal, for 7 days, starting 6 days before the reserpine injection) could improve the worsened social memory of reserpine-treated rats. Also, EGCG treatment reduced reserpine-induced lipid peroxidation and enhanced the antioxidation power in the hippocampi of reserpine-treated rats. These results suggest a protective effect of EGCG in treating reserpine-induced impairment of memory, most probably through its powerful antioxidative activities. Accordingly, EGCG may hold a clinically relevant value in preventing reserpine-induced cognitive dysfunction.

Long-term electromagnetic pulse exposure induces Abeta deposition and cognitive dysfunction through oxidative stress and overexpression of APP and BACE1.

PubMed

Jiang, Da-Peng; Li, Jin-Hui; Zhang, Jie; Xu, Sheng-Long; Kuang, Fang; Lang, Hai-Yang; Wang, Ya-Feng; An, Guang-Zhou; Li, Jing; Guo, Guo-Zhen

2016-07-01

A progressively expanded literature has been devoted in the past years to the noxious or beneficial effects of electromagnetic field (EMF) to Alzheimer׳s disease (AD). This study concerns the relationship between electromagnetic pulse (EMP) exposure and the occurrence of AD in rats and the underlying mechanisms, focusing on the role of oxidative stress (OS). 55 healthy male Sprague Dawley (SD) rats were used and received continuous exposure for 8 months. Morris water maze (MWM) test was conducted to test the ability of cognitive and memory. The level of OS was detected by superoxide dismutase (SOD) activity and glutathione (GSH) content. We found that long-term EMP exposure induced cognitive damage in rats. The content of β-amyloid (Aβ) protein in hippocampus was increased after long-term EMP exposure. OS of hippocampal neuron was detected. Western blotting and immunohistochemistry (IHC) assay showed that the content of Aβ protein and its oligomers in EMP-exposed rats were higher than that of sham-exposed rats. The content of Beta Site App Cleaving Enzyme (BACE1) and microtubule-associated protein 1 light chain 3-II (LC3-II) in EMP-exposed rats hippocampus were also higher than that of sham-exposed rats. SOD activity and GSH content in EMP-exposed rats were lower than sham-exposed rats (p<0.05). Several mechanisms were proposed based on EMP exposure-induced OS, including increased amyloid precursor protein (APP) aberrant cleavage. Although further study is needed, the present results suggest that long-term EMP exposure is harmful to cognitive ability in rats and could induce AD-like pathological manifestation. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of in utero and lactational exposure to SbV on rat neurobehavioral development and fertility.

PubMed

Coelho, Deise R; De-Carvalho, Rosangela R; Rocha, Rafael C C; Saint'Pierre, Tatiana D; Paumgartten, Francisco J R

2014-12-01

Meglumine antimoniate (MA) is a pentavalent antimony drug used to treat leishmaniases. We investigated the neurobehavioral development, sexual maturation and fertility of the offspring of MA-treated rats. Dams were administered MA (0, 75, 150, 300 mg Sb(V)/kg body wt/d, sc) from gestation day 0, throughout parturition and lactation, until weaning. At the highest dose, MA reduced the birth weight and the number of viable newborns. In the male offspring, MA did not impair development (somatic, reflex maturation, weight gain, puberty onset, open field test), sperm count, or reproductive performance. Except for a minor effect on body weight gain and vertical exploration in the open field, MA also did not affect the development of female offspring. Measurements of the Sb levels (ICP-MS) in the blood of MA-treated female rats and their offspring demonstrated that Sb is transferred to the fetuses via the placenta and to the suckling pups via milk. Copyright © 2014 Elsevier Inc. All rights reserved.

Enhanced inhibitory effects of TBT chloride on the development of F1 rats.

PubMed

Asakawa, H; Tsunoda, M; Kaido, T; Hosokawa, M; Sugaya, C; Inoue, Y; Kudo, Y; Satoh, T; Katagiri, H; Akita, H; Saji, M; Wakasa, M; Negishi, T; Tashiro, T; Aizawa, Y

2010-05-01

Neurotoxicity is one of the major effects of tributyltin (TBT). The effects on the next generation of F(1) rats exposed to TBT via the placenta and their dams' milk may be stronger than those on adults. Pregnant Wister rats were exposed to TBT at 0 and 125 ppm in their food. Half of the female F(1) rats in both groups were exposed to TBT at 125 ppm in their food from 9 to 15 weeks of age. Female F(1) rats were divided into the following groups: the control-control (CC) group, with no exposure; the TBT-control (TC) group, exposed to TBT via the placenta and their dams' milk; the control-TBT (CT) group, exposed to TBT via their food from 9 to 15 weeks of age; and the TBT-TBT (TT) group, exposed to TBT via the placenta, their dams' milk, and their food (n = 10/group). After administration, an open-field test and prepulse inhibition (PPI) test were performed at 15 weeks of age. The mean body weights of the TC and TT groups were significantly lower than that of the CC group from 9 to 15 weeks of age. The mean relative thymus weight of the TC and TT groups was significantly lower than that of the CC group. In the open-field test, a marked decrease in the total locomotion distance was observed in the TT group. The mean values in the TT and TC groups were significantly lower than that in the CC group. For the locomotion distance between 15 and 20 min, the mean values in the CT, TC, and TT groups were significantly lower than that in the CC group. The mean locomotor distance between 25 and 30 min in the TT group was significantly lower than that in the CC and TC groups. The mean values of instances of wall rearing in the TC, CT, and TT groups were significantly lower than that in the CC group. The mean value of face washing or body washing in the TT group was significantly lower than that in the CT group. There were no significant differences in indexes of the PPI test. Exposure to TBT via the placenta and their dams' milk inhibited the development of F(1) rats, which continued after weaning. Inhibition of the rats' activity induced by exposure to TBT via the placenta and their dams' milk and/or via their food was suggested. The effects were most evident in the TT group.

Importance of neural mechanisms in colonic mucosal and muscular dysfunction in adult rats following neonatal colonic irritation.

PubMed

Chaloner, A; Rao, A; Al-Chaer, E D; Greenwood-Van Meerveld, B

2010-02-01

Previous studies have shown that early life trauma induced by maternal separation or colonic irritation leads to hypersensitivity to colorectal distension in adulthood. We tested the hypothesis that repetitive colorectal distension in neonates leads to abnormalities in colonic permeability and smooth muscle function in the adult rat. In neonatal rats, repetitive colorectal distension was performed on days 8, 10, and 12. As adults, stool consistency was graded from 0 (formed stool) to 3 (liquid stool). Colonic tissue was isolated for histology and myeloperoxidase levels. The colonic mucosa was placed in modified Ussing chambers for measurements of permeability and short-circuit current responses to forskolin, electrical field stimulation, and carbachol. Segments of colonic musculature were placed in organ baths and contractile response to potassium chloride, electrical field stimulation, and carbachol were determined. In adult rats that experienced neonatal colonic irritation, no significant changes in colonic histology or myeloperoxidase activity were observed; however, stool consistency scores were increased. Mucosal permeability, measured as an increase in basal conductance, was significantly increased but no changes in short-circuit current responses were observed. In adulthood, rats that underwent colorectal distension as neonates exhibited an elevated smooth muscle contractile response to potassium chloride, but no changes in response to electrical field stimulation or carbachol. In summary, neonatal colonic irritation, shown previously to produce colonic hypersensitivity, leads to significant alterations in colonic mucosal and smooth muscle function characterized by loose stools, increased mucosal permeability, and increased smooth muscle contractility in the absence of colon inflammation in adulthood. Published by Elsevier Ltd.

A Role for 2-Arachidonoylglycerol and Endocannabinoid Signaling in the Locomotor Response to Novelty Induced by Olfactory Bulbectomy

PubMed Central

Eisenstein, Sarah A.; Clapper, Joson R.; Holmes, Philip V.; Piomelli, Daniele; Hohmann, Andrea G.

2010-01-01

Bilateral olfactory bulbectomy (OBX) in rodents produces behavioral and neurochemical changes associated clinically with depression and schizophrenia. Most notably, OBX induces hyperlocomotion in response to the stress of exposure to a novel environment. We examined the role of the endocannabinoid system in regulating this locomotor response in OBX and sham-operated rats. In our study, OBX-induced hyperactivity was restricted to the first 3 min of the open field test, demonstrating the presence of novelty (0–3 min) and habituation (3–30 min) phases of the open field locomotor response. Levels of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide were decreased in the ventral striatum, a brain region deafferented by OBX, whereas cannabinoid receptor densities were unaltered. In sham-operated rats, 2-AG levels in the ventral striatum were negatively correlated with distance traveled during the novelty phase. Thus, low levels of 2-AG are reflected in a hyperactive open field response. This correlation was not observed in OBX rats. Conversely, 2-AG levels in endocannabinoid-compromised OBX rats correlated with distance traveled during the habituation phase. In OBX rats, pharmacological blockade of cannabinoid CB1 receptors with either AM251 (1 mg kg−1 i.p.) or rimonabant (1 mg kg−1 i.p.) increased distance traveled during the habituation phase. Thus, blockade of endocannabinoid signaling impairs habituation of the hyperlocomotor response in OBX, but not sham-operated, rats. By contrast, in sham-operated rats, effects of CB1 antagonism were restricted to the novelty phase. These findings suggest that dysregulation in the endocannabinoid system, and 2-AG in particular, is implicated in the hyperactive locomotor response induced by OBX. Our studies suggest that drugs that enhance 2-AG signaling, such as 2-AG degradation inhibitors, might be useful in human brain disorders modeled by OBX. PMID:20044005

Transmission of Guanarito and Pirital Viruses among Wild Rodents, Venezuela

PubMed Central

Milazzo, Mary L.; Cajimat, Maria N.B.; Duno, Gloria; Duno, Freddy; Utrera, Antonio

2011-01-01

Samples from rodents captured on a farm in Venezuela in February 1997 were tested for arenavirus, antibody against Guanarito virus (GTOV), and antibody against Pirital virus (PIRV). Thirty-one (48.4%) of 64 short-tailed cane mice (Zygodontomys brevicauda) were infected with GTOV, 1 Alston’s cotton rat (Sigmodon alstoni) was infected with GTOV, and 36 (64.3%) of 56 other Alston’s cotton rats were infected with PIRV. The results of analyses of field and laboratory data suggested that horizontal transmission is the dominant mode of GTOV transmission in Z. brevicauda mice and that vertical transmission is an important mode of PIRV transmission in S. alstoni rats. The results also suggested that bodily secretions and excretions from most GTOV-infected short-tailed cane mice and most PIRV-infected Alston’s cotton rats may transmit the viruses to humans. PMID:22172205

Post-training scopolamine treatment induced maladaptive behavior in open field habituation task in rats.

PubMed

Popović, Natalija; Caballero-Bleda, María; Popović, Miroljub

2014-01-01

The effects of scopolamine on memory consolidation are controversial and depend on several factors (i.e. site of administration, time of administration and testing, dose, cognitive task, experimental protocol, specie, strain, etc.). Generally, the range dose of systemic administered scopolamine, used in memory consolidation studies, has varied from 0.05 to 50 mg/kg. However, according to the literature, the most frequently used doses of scopolamine efficient on memory consolidation, are 1 and 30 mg/kg, low and high doses, respectively. In open field habituation studies only lower doses of scopolamine were used to test memory consolidation. Therefore, in the present study we compared the effects of low (1 mg/kg) and high (30 mg/kg) scopolamine dose, on the open field habituation task, in male Wistar rats. Scopolamine was administered immediately after the acquisition task and animals were retested 48 h later on. On the retested day, the ambulation and rearing in the open field decreased in the same manner in all tested groups. In saline- and 1 mg/kg scopolamine-treated animals, the time spent in grooming significantly decreased in the habituation task, while the same parameter significantly increased in animals treated with 30 mg/kg of scopolamine. The defecation rate significantly decreased (control group), maintained (1 mg/kg of scopolamine treated animals) or significantly increased (30 mg/kg of scopolamine treated group) on retention test. In conclusion, the present data suggest that post-training scopolamine administration does not affect locomotion neither exploration in the habituation to a novel environment, but increases defecation and grooming, two behaviours associated with fearful and stressful situations.

Enduring effects of post-weaning rearing condition on depressive- and anxiety-like behaviors and motor activity in male rats.

PubMed

Mosaferi, Belal; Babri, Shirin; Ebrahimi, Hadi; Mohaddes, Gisou

2015-04-01

Environmental manipulation at early critical periods could have long-lasting effects. In spite of the great interest in the biological effects of the environmental condition so far, its long-lasting effects are less documented. This study looks at the enduring effects of rearing condition on tasks that measure affective responses and exploratory behavior in male Wistar rats. The animals were reared from weaning to adulthood in an enriched environment, standard laboratory condition, or isolated condition. Then, all rats were housed in standard laboratory cages to provide a common environment, and successively exposed to different tests between 0 and 11 weeks post-manipulation. The open field test indicated a more efficient exploratory behavior in the enriched group, and an enhanced spontaneous motor activity in both standard and isolated groups. In addition, rats reared in standard condition showed heightened motor activity in forced swimming test and elevated plus maze. Forced swimming test showed an antidepressive-like effect in the enriched environment group by increased climbing behavior. In respect to the anxiety behavior, environmental enrichment improved threat detection ability. It is concluded that rearing condition from weaning to adulthood has important and long-lasting effects on depressive- and anxiety-like and exploratory behaviors as well as motor activity. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of neonatal novelty exposure on sexual behavior, fear, and stress-response in adult rats.

PubMed

Benetti, Fernando; Andrade de Araujo, Paulo; Sanvitto, Gilberto Luiz; Lucion, Aldo Bolten

2007-04-01

Environmental stimuli in early life may result in permanent behavioral and physiological changes. Present study evaluated the effects of exposing pups to a novel environment on behaviors (open-field test and sexual behavior) and prolactin stress-responses in adult male rats. Half of a litter was daily removed outside (OUT) from the nest and stimulated by handling for 3 min, while the other half remained inside (IN) the nest and was also handled for the same period during the first 10 days postpartum. Maternal behavior after all the pups were returned to the nest was not different between IN and OUT littermates. In adulthood, OUT males showed increased general and central locomotion activity in the open-field test, reduced sexual behavior, and attenuated prolactin secretion in response to restraint stress compared with the IN littermates. The repeated exposition of rat pups to a novel environment is a causal factor for the long-lasting behavioral and endocrine changes. The premature exposition of the pup to unfamiliar environments decreases fear and stress-response, and also reduces sexual behavior. We suggest that the absence of the odor of the mother may be crucial to explain the effects detected in adulthood. (c) 2007 Wiley Periodicals, Inc.

Pharmacokinetic, Ambulatory, and Hyperthermic Effects of 3,4-Methylenedioxy-N-Methylcathinone (Methylone) in Rats.

PubMed

Štefková, Kristýna; Židková, Monika; Horsley, Rachel R; Pinterová, Nikola; Šíchová, Klára; Uttl, Libor; Balíková, Marie; Danda, Hynek; Kuchař, Martin; Páleníček, Tomáš

2017-01-01

Methylone (3,4-methylenedioxy- N -methylcathinone) is a synthetic cathinone analog of the recreational drug ecstasy. Although it is marketed to recreational users as relatively safe, fatalities due to hyperthermia, serotonin syndrome, and multi-organ system failure have been reported. Since psychopharmacological data remain scarce, we have focused our research on pharmacokinetics, and on a detailed evaluation of temporal effects of methylone and its metabolite nor-methylone on behavior and body temperature in rats. Methylone [5, 10, 20, and 40 mg/kg subcutaneously (s.c.)] and nor-methylone (10 mg/kg s.c.) were used in adolescent male Wistar rats across three behavioral/physiological procedures and in two temporal windows from administration (15 and 60 min) in order to test: locomotor effects in the open field, sensorimotor gating in the test of prepulse inhibition (PPI), and effects on rectal temperature in individually and group-housed rats. Serum and brain pharmacokinetics after 10 mg/kg s.c. over 8 h were analyzed using liquid chromatography mass spectrometry. Serum and brain levels of methylone and nor-methylone peaked at 30 min after administration, both drugs readily penetrated the brain with serum: brain ratio 1:7.97. Methylone dose-dependently increased overall locomotion. It also decrease the amount of time spent in the center of open field arena in dose 20 mg/kg and additionally this dose induced stereotyped circling around the arena walls. The maximum of effects corresponded to the peak of its brain concentrations. Nor-methylone had approximately the same behavioral potency. Methylone also has weak potency to disturb PPI. Behavioral testing was not performed with 40 mg/kg, because it was surprisingly lethal to some animals. Methylone 10 and 20 mg/kg s.c. induced hyperthermic reaction which was more pronounced in group-housed condition relative to individually housed rats. To conclude, methylone increased exploration and/or decreased anxiety in the open field arena and with nor-methylone had short duration of action with effects typical for mixed indirect dopamine-serotonin agonists such as 3,4-metyhlenedioxymethamphetamine (MDMA) or amphetamine. Given the fact that the toxicity was even higher than the known for MDMA and that it can cause hyperthermia it possess a threat to users with the risk for serotonin syndrome especially when used in crowded conditions.

Neonatal immune activation by lipopolysaccharide causes inadequate emotional responses to novel situations but no changes in anxiety or cognitive behavior in Wistar rats.

PubMed

Vojtechova, Iveta; Petrasek, Tomas; Maleninska, Kristyna; Brozka, Hana; Tejkalova, Hana; Horacek, Jiri; Stuchlik, Ales; Vales, Karel

2018-05-02

Infection during the prenatal or neonatal stages of life is considered one of the major risk factors for the development of mental diseases such as schizophrenia or autism. However, the impacts of such an immune challenge on adult behavior are still not clear. In our study, we used a model of early postnatal immune activation by the application of bacterial endotoxin lipopolysaccharide (LPS) to rat pups at a dose of 2 mg/kg from postnatal day (PD) 5 to PD 9. In adulthood, the rats were tested in a battery of tasks probing various aspects of behavior: spontaneous activity (open field test), social behavior (social interactions and female bedding exploration), anxiety (elevated plus maze), cognition (active place avoidance in Carousel) and emotional response (ultrasonic vocalization recording). Moreover, we tested sensitivity to acute challenge with MK-801, a psychotomimetic drug. Our results show that the application of LPS led to increased self-grooming in the female bedding exploration test and inadequate emotional reactions in Carousel maze displayed by ultrasonic vocalizations. However, it did not have serious consequences on exploration, locomotion, social behavior or cognition. Furthermore, exposition to MK-801 did not trigger social or cognitive deficits in the LPS-treated rats. We conclude that the emotional domain is the most sensitive to the changes induced by neonatal immune activation in rats, including a disrupted response to novel and stressful situations in early adulthood (similar to that observed in human patients suffering from schizophrenia or autism), while other aspects of tested behavior remain unaffected. Copyright © 2018 Elsevier B.V. All rights reserved.

Preference test of sound among multiple alternatives in rats.

PubMed

Soga, Ryo; Shiramatsu, Tomoyo Isoguchi; Takahashi, Hirokazu

2018-01-01

Conditioned place preference (CPP) tests in rodents have been well established to measure preference induced by secondary reinforcing properties, but conventional assays are not sensitive enough to measure innate, weak preference, or the primary reinforcing property of a conditioned stimulus. We designed a novel CPP assay with better sensitivity and efficiency in quantifying and ranking preference of particular sounds among multiple alternatives. Each test tone was presented according to the location of free-moving rats in the arena, where assignment of location to each tone changed in every 20-s session. We demonstrated that our assay was able to rank tone preference among 4 alternatives within 12.5 min (125 s (habituation) + 25 s/sessions × 25 sessions). In order to measure and rank sound preference, we attempted to use sojourn times with each test sound ([Formula: see text]), and a preference index (PI) based on transition matrices of initial and end sounds in every session. Both [Formula: see text] and PI revealed similar trends of innate preference in which rats preferred test conditions in the following order: silence, 40-, 20-, then 10-kHz tones. Further, rats exhibited a change in preference after an classical conditioning of the 20-kHz tone with a rewarding microstimulation of the dopaminergic system. We also demonstrated that PI was a more robust and sensitive indicator than [Formula: see text] when the locomotion activity level of rats became low due to habituation to the assay repeated over sessions. Thus, our assay offers a novel method of evaluating auditory preference that is superior to conventional CPP assays, offering promising prospects in the field of sensory neuroscience.

Can coconut oil and treadmill exercise during the critical period of brain development ameliorate stress-related effects on anxiety-like behavior and episodic-like memory in young rats?

PubMed

da Silva, Débora de Cássia; Tavares, Maryane Gabriela; do Nascimento, Camila Karina Brito; Lira, Eduardo Carvalho; Dos Santos, Ângela Amâncio; Maia, Luciana Maria Silva de Seixas; Batista-de-Oliveira Hornsby, Manuella

2018-03-01

Virgin coconut oil (CO) and treadmill exercise have been reported to improve memory performance in young rats. CO has also been associated with antistress properties in young, stressed mice. Therefore, in this study we aimed to investigate whether CO and treadmill exercise could synergistically ameliorate the effects of chronic stress on anxiety-like behavior and episodic-like memory in young rats. The rats received CO and were exercised (Ex) from the 15 th to the 45 th day of life. The animals were supplemented with CO (10 mL kg -1 day -1 ) or a vehicle (V, distilled water and 0.009% Cremophor) via oral gavage. The Ex animals were placed for 30 min day -1 on a treadmill, with the speed gradually increasing from the first week to the last. From the 46 th to the 54 th postnatal day, with the exception of the 51 st and the 52 nd day, all rats were subjected to restraint stress. Afterwards, all rats underwent the open-field test to evaluate locomotor activity and anxiety-like behavior. To evaluate episodic-like memory, all animals underwent tests to recognize object identity and special location. Lastly, lipid profile and murinometric parameters were evaluated. A two-way ANOVA test followed by a Tukey test demonstrated that the CO&Ex group explored more of the unprotected central area of the OFT (27.04 ± 4.03 s, p < 0.01), when compared to the control group (15.36 ± 2.54 s). CO&Ex spent more time exploring the novel location of the object (71.62 ± 3.04%, p < 0.01), when compared to the control group (58.62 ± 2.48%). CO and exercise during lactation can ameliorate the effects of stress on anxiety-like behavior and episodic-like memory in young rats.

Supplemental dietary choline during development exerts antidepressant-like effects in adult female rats

PubMed Central

Glenn, Melissa J.; Adams, Raven S.; McClurg, Lauren

2012-01-01

Perinatal choline supplementation in rats is neuroprotective against insults such as fetal alcohol exposure, seizures, and advanced age. In the present study we explored whether dietary choline supplementation may also confer protection from psychological challenges, like stress, and act as a natural buffer against stress-linked psychological disorders, like depression. We previously found that choline supplementation increased adult hippocampal neurogenesis, a function compromised by stress, lowered in depression, and boosted by antidepressants; and increased levels of growth factors linked to depression, like brain-derived neurotrophic factor. Together, these were compelling reasons to study the role of choline in depressed mood. To do this, we treated rats with a choline supplemented diet (5 mg/kg choline chloride in AIN76A) prenatally on embryonic days 10–22, on postnatal days (PD) 25–50, or as adults from PD75 onward. Outside of these treatment periods rats were fed a standard diet (1.1 mg/kg choline chloride in AIN76A); control rats consumed only this diet throughout the study. Starting on PD100 rats’ anxiety-like responses to an open field, learning in a water maze, and reactivity to forced swimming were assessed. Rats given choline supplementation during pre- or post-natal development, but not adult-treated rats, were less anxious in the open field and less immobile in the forced swim test than control rats. These effects were not mediated by a learning deficit as all groups performed comparably and well in the water maze. Thus, we offer compelling support for the hypothesis that supplemental dietary choline, at least when given during development, may inoculate an individual against stress and major psychological disorders, like depression. PMID:22305146

Reversal-specific learning impairments after a binge regimen of methamphetamine in rats: possible involvement of striatal dopamine.

PubMed

Izquierdo, Alicia; Belcher, Annabelle M; Scott, Lori; Cazares, Victor A; Chen, Jack; O'Dell, Steven J; Malvaez, Melissa; Wu, Tiffany; Marshall, John F

2010-01-01

A growing body of evidence indicates that protracted use of methamphetamine (mAMPH) causes long-term impairments in cognitive function in humans. Aside from the widely reported problems with attention, mAMPH users exhibit learning and memory deficits, particularly on tasks requiring response control. Although binge mAMPH administration to animals results in cognitive deficits, few studies have attempted to test behavioral flexibility in animals after mAMPH exposure. The aim of this study was to evaluate whether mAMPH would produce impairments in two tasks assessing flexible responding in rats: a touchscreen-based discrimination-reversal learning task and an attentional set shift task (ASST) based on a hallmark test of executive function in humans, the Wisconsin Card Sort. We treated male Long-Evans rats with a regimen of four injections of 2 mg/kg mAMPH (or vehicle) within a single day, a dosing regimen shown earlier to produce object recognition impairments. We then tested them on (1) reversal learning after pretreatment discrimination learning or (2) the ASST. Early reversal learning accuracy was impaired in mAMPH-treated rats. MAMPH pretreatment also selectively impaired reversal performance during ASST testing, leaving set-shifting performance intact. Postmortem analysis of [(125)I]RTI-55 binding revealed small (10-20%) but significant reductions in striatal dopamine transporters produced by this mAMPH regimen. Together, these results lend new information to the growing field documenting impaired cognition after mAMPH exposure, and constitute a rat model of the widely reported decision-making deficits resulting from mAMPH abuse seen in humans.

A sensitive and reliable test instrument to assess swimming in rats with spinal cord injury.

PubMed

Xu, Ning; Åkesson, Elisabet; Holmberg, Lena; Sundström, Erik

2015-09-15

For clinical translation of experimental spinal cord injury (SCI) research, evaluation of animal SCI models should include several sensorimotor functions. Validated and reliable assessment tools should be applicable to a wide range of injury severity. The BBB scale is the most widely used test instrument, but similar to most others it is used to assess open field ambulation. We have developed an assessment tool for swimming in rats with SCI, with high discriminative power and sensitivity to functional recovery after mild and severe injuries, without need for advanced test equipment. We studied various parameters of swimming in four groups of rats with thoracic SCI of different severity and a control group, for 8 weeks after surgery. Six parameters were combined in a multiple item scale, the Karolinska Institutet Swim Assessment Tool (KSAT). KSAT scores for all SCI groups showed consistent functional improvement after injury, and significant differences between the five experimental groups. The internal consistency, the inter-rater and the test-retest reliability were very high. The KSAT score was highly correlated to the cross-section area of white matter spared at the injury epicenter. Importantly, even after 8 weeks of recovery the KSAT score reliably discriminated normal animals from those inflicted by the mildest injury, and also displayed the recovery of the most severely injured rats. We conclude that this swim scale is an efficient and reliable tool to assess motor activity during swimming, and an important addition to the methods available for evaluating rat models of SCI. Copyright © 2015 Elsevier B.V. All rights reserved.

Nano-architectural Alterations in Mucus Layer Fecal Colonocytes in Field Carcinogenesis: Potential for Screening

PubMed Central

Roy, Hemant K.; Damania, Dhwanil P.; DelaCruz, Mart; Kunte, Dhananjay P.; Subramanian, Hariharan; Crawford, Susan E.; Tiwari, Ashish K.; Wali, Ramesh K.; Backman, Vadim

2013-01-01

Current fecal tests (occult blood, methylation, DNA mutations) target minute amounts of tumor products among a large amount of fecal material and thus have suboptimal performance. Our group has focused on exploiting field carcinogenesis as a modality to amplify the neoplastic signal. Specifically, we have demonstrated that endoscopically normal rectal brushings have striking nano-architectural alterations which are detectable utilizing a novel optical technique, partial wave spectroscopic microscopy (PWS). We therefore wished to translate this approach to a fecal assay. We examined mucus layer fecal colonocytes (MLFCs) at preneoplastic and neoplastic time-points (confirmed with rat colonoscopy) in the azoxymethane (AOM)-treated rat model and conducted PWS analysis to derive the nano-architectural parameter, disorder strength (Ld). We confirmed these results with studies in a genetic model (the Pirc rat). We demonstrated that MLFC appeared microscopically normal, consistent with field carcinogenesis. Ld was elevated at an early time point (5 weeks post-AOM injection, effect size = 0.40, p value = 0.024) and plateaued prior to adenoma formation (10 weeks post-AOM, effect size =0.66, p=0.001), with no dramatic increase once tumors developed. We replicated these data in the pre-neoplastic Pirc rat with an effect size in the MLFC that replicated the rectal brushings (increase versus age-matched controls of 62 versus 74%, respectively). We provide the first demonstration of a biophotonics approach to fecal assay. Furthermore, targeting the nano-architectural changes of field carcinogenesis rather than the detection of tumor products may provide a novel paradigm for colorectal cancer screening. PMID:23983085

Social isolation and chronic handling alter endocannabinoid signaling and behavioral reactivity to context in adult rats

PubMed Central

Sciolino, Natale R.; Bortolato, Marco; Eisenstein, Sarah A.; Fu, Jin; Oveisi, Fariba; Hohmann, Andrea G.; Piomelli, Daniele

2010-01-01

Social deprivation in early life disrupts emotionality and attentional processes in humans. Rearing rats in isolation reproduces some of these abnormalities, which are attenuated by daily handling. However, the neurochemical mechanisms underlying these responses remain poorly understood. We hypothesized that post-weaning social isolation alters the endocannabinoid system, a neuromodulatory system that controls emotional responding. We characterized behavioral consequences of social isolation and evaluated whether handling would reverse social isolation-induced alterations in behavioral reactivity to context and the endocannabinoid system. At weaning, pups were single or group housed and concomitantly handled or not handled daily until adulthood. Rats were tested in emotionality- and attentional-sensitive behavioral assays (open field, elevated plus maze, startle and prepulse inhibition). Cannabinoid receptor densities and endocannabinoid levels were quantified in a separate group of rats. Social isolation negatively altered behavioral responding. Socially-isolated rats that were handled showed less deficits in the open field, elevated plus maze, and prepulse inhibition tests. Social isolation produced site-specific alterations (supraoptic nucleus, ventrolateral thalamus, rostral striatum) in cannabinoid receptor densities compared to group rearing. Handling altered the endocannabinoid system in neural circuitry controlling emotional expression. Handling altered endocannabinoid content (prefrontal and piriform cortices, nucleus accumbens) and cannabinoid receptor densities (lateral globus pallidus, cingulate and piriform cortices, hippocampus) in a region-specific manner. Some effects of social isolation on the endocannabinoid system were moderated by handling. Isolates were unresponsive to handling-induced increases in cannabinoid receptor densities (caudal striatum, anterior thalamus), but were sensitive to handling-induced increases in endocannabinoid content (piriform cortex), compared to group-reared rats. Our findings suggest alterations in the endocannabinoid system may contribute to the abnormal isolate phenotype. Handling modifies the endocannabinoid system and behavioral reactivity to context, but surmounts only some effects of social isolation. These data implicate a pivotal role for the endocannabinoid system in stress adaptation and emotionality-related disturbances. PMID:20394803

Impairment of decision making and disruption of synchrony between basolateral amygdala and anterior cingulate cortex in the maternally separated rat.

PubMed

Cao, Bing; Wang, Jun; Zhang, Xu; Yang, Xiangwei; Poon, David Chun-Hei; Jelfs, Beth; Chan, Rosa H M; Wu, Justin Che-Yuen; Li, Ying

2016-12-01

There is considerable evidence to suggest early life experiences, such as maternal separation (MS), play a role in the prevalence of emotional dysregulation and cognitive impairment. At the same time, optimal decision making requires functional integrity between the amygdala and anterior cingulate cortex (ACC), and any dysfunction of this system is believed to induce decision-making deficits. However, the impact of MS on decision-making behavior and the underlying neurophysiological mechanisms have not been thoroughly studied. As such, we consider the impact of MS on the emotional and cognitive functions of rats by employing the open-field test, elevated plus-maze test, and rat gambling task (RGT). Using multi-channel recordings from freely behaving rats, we assessed the effects of MS on the large scale synchrony between the basolateral amygdala (BLA) and the ACC; while also characterizing the relationship between neural spiking activity and the ongoing oscillations in theta frequency band across the BLA and ACC. The results indicated that the MS rats demonstrated anxiety-like behavior. While the RGT showed a decrease in the percentage of good decision-makers, and an increase in the percentage of poor decision-makers. Electrophysiological data revealed an increase in the total power in the theta band of the LFP in the BLA and a decrease in theta power in the ACC in MS rats. MS was also found to disrupt the spike-field coherence of the ACC single unit spiking activity to the ongoing theta oscillations in the BLA and interrupt the synchrony in the BLA-ACC pathway. We provide specific evidence that MS leads to decision-making deficits that are accompanied by alteration of the theta band LFP in the BLA-ACC circuitries and disruption of the neural network integrity. These observations may help revise fundamental notions regarding neurophysiological biomarkers to treat cognitive impairment induced by early life stress. Copyright © 2016 Elsevier Inc. All rights reserved.

The Defecation Index as a Measure of Emotionality: Questions Raised by HPA Axis and Prolactin Response to Stress in the Maudsley Model.

PubMed

Blizard, David A; Eldridge, J Charles; Jones, Byron C

2015-05-01

The Maudsley Reactive and Maudsley Non-Reactive strains have been selectively bred for differences in open-field defecation (OFD), a putative index of stress. We investigated whether variations in the hypothalamic-pituitary-adrenal (HPA) axis are correlated with strain differences in OFD in the Maudsley model. Exposure to the open-field test did not result in increases in ACTH in male rats of either strain and there were no strain differences in the large increases in ACTH and corticosteroid that occurred in response to intermittent footshock. Parallel studies of prolactin showed that Maudsley Reactive rats had greater response to the open-field and to footshock than Maudsley Non-Reactive rats. The lack of correlation between strain differences in OFD and reactivity of the HPA axis is consistent with the idea that HPA response to stress and OFD reflect the output of different neural systems and that individual differences in emotionality, as indexed by OFD do not influence other measures of stress-reactivity in a simple manner, if at all. The reactivity of the prolactin system to the open-field test and lack of response of ACTH to the same situation is consistent with the idea that the prolactin system is sensitive to lower levels of stress than the HPA axis, a finding at variance with the presumed extreme sensitivity of the latter system. Earlier comparisons of the HPA axis in these strains implicate local factors such as neuropeptide-Y peptide in the adrenal in attenuating the response of the adrenal cortex to ACTH and hints at the complexity of regulation of the HPA axis.

Stress-related endocrinological and psychopathological effects of short- and long-term 50Hz electromagnetic field exposure in rats.

PubMed

Szemerszky, Renáta; Zelena, Dóra; Barna, István; Bárdos, György

2010-01-15

It is believed that different electromagnetic fields do have beneficial and harmful biological effects. The aim of the present work was to study the long-term consequences of 50 Hz electromagnetic field (ELF-EMF) exposure with special focus on the development of chronic stress and stress-induced psychopathology. Adult male Sprague-Dawley rats were exposed to ELF-EMF (50 Hz, 0.5 mT) for 5 days, 8h daily (short) or for 4-6 weeks, 24h daily (long). Anxiety was studied in elevated plus maze test, whereas depression-like behavior of the long-treated group was examined in the forced swim test. Some days after behavioral examination, the animals were decapitated among resting conditions and organ weights, blood hormone levels as well as proopiomelanocortin mRNA level from the anterior lobe of the pituitary gland were measured. Both treatments were ineffective on somatic parameters, namely none of the changes characteristic to chronic stress (body weight reduction, thymus involution and adrenal gland hypertrophy) were present. An enhanced blood glucose level was found after prolonged ELF-EMF exposure (p=0.013). The hormonal stress reaction was similar in control and short-term exposed rats, but significant proopiomelanocortin elevation (p<0.000) and depressive-like behavior (enhanced floating time; p=0.006) were found following long-term ELF-EMF exposure. Taken together, long and continuous exposure to relatively high intensity electromagnetic field may count as a mild stress situation and could be a factor in the development of depressive state or metabolic disturbances. Although we should stress that the average intensity of the human exposure is normally much smaller than in the present experiment.

Minocycline produced antidepressant-like effects on the learned helplessness rats with alterations in levels of monoamine in the amygdala and no changes in BDNF levels in the hippocampus at baseline.

PubMed

Arakawa, Shiho; Shirayama, Yukihiko; Fujita, Yuko; Ishima, Tamaki; Horio, Mao; Muneoka, Katsumasa; Iyo, Masaomi; Hashimoto, Kenji

2012-01-01

Previous studies have indicated that minocycline might function as an antidepressant drug. The aim of this study was to evaluate the antidepressant-like effects of minocycline, which is known to suppress activated microglia, using learned helplessness (LH) rats (an animal model of depression). Infusion of minocycline into the cerebral ventricle of LH rats induced antidepressant-like effects. However, infusion of minocycline into the cerebral ventricle of naïve rats did not produce locomotor activation in the open field tests, suggesting that the antidepressant-like effects of minocycline were not attributed to the enhanced locomotion. LH rats showed significantly higher serotonin turnover in the orbitofrontal cortex and lower levels of brain-derived neurotrophic factor (BDNF) in the hippocampus than control rats. However, these alterations in serotonin turnover and BDNF expression remained unchanged after treatment with minocycline. On the contrary, minocycline treatment of LH rats induced significant increases in the levels of dopamine and its metabolites in the amygdala when compared with untreated LH rats. Taken together, minocycline may be a therapeutic drug for the treatment of depression. Copyright © 2011 Elsevier Inc. All rights reserved.

Determining the mechanical properties of rat skin with digital image speckle correlation.

PubMed

Guan, E; Smilow, Sarah; Rafailovich, Miriam; Sokolov, Jonathan

2004-01-01

Accurate measurement of the mechanical properties of skin has numerous implications in surgical repair, dermal disorders and the diagnosis and treatment of trauma to the skin. Investigation of facial wrinkle formation, as well as research in the areas of skin aging and cosmetic product assessment can also benefit from alternative methodologies for the measurement of mechanical properties. A noncontact, noninvasive technique, digital image speckle correlation (DISC), has been successfully introduced to measure the deformation field of a skin sample loaded by a material test machine. With the force information obtained from the loading device, the mechanical properties of the skin, such as Young's modulus, linear limitation and material strength, can be calculated using elastic or viscoelastic theory. The DISC method was used to measure the deformation of neonatal rat skin, with and without a glycerin-fruit-oil-based cream under uniaxial tension. Deformation to failure procedure of newborn rat skin was recorded and analyzed. Single skin layer failures were observed and located by finding the strain concentration. Young's moduli of freshly excised rat skin, cream-processed rat skin and unprocessed rat skin, 24 h after excision, were found with tensile tests to be 1.6, 1.4 and 0.7 MPa, respectively. Our results have shown that DISC provides a novel technique for numerous applications in dermatology and reconstructive surgeries. Copyright 2004 S. Karger AG, Basel

Sub-anesthetic doses of ketamine exert antidepressant-like effects and upregulate the expression of glutamate transporters in the hippocampus of rats.

PubMed

Zhu, Xianlin; Ye, Gang; Wang, Zaiping; Luo, Jie; Hao, Xuechao

2017-02-03

Clinical studies on the role of the glutamatergic system in the pathogenesis of depression found that ketamine induces an antidepressant response, but the molecular mechanisms remain unclear. The present study investigated the effects of sub-anesthetic doses of ketamine on the glutamate reuptake function in the rat hippocampus. Chronic unpredictable mild stress (CUMS) was applied to construct animal models of depression. Sixty adult male Sprague-Dawley rats were randomly assigned to 5 groups and received a different regimen of CUMS and ketamine (10, 25, and 50mg/kg) treatment. The sucrose preference test and open-field test were used to assess behavioral changes. The expression levels of excitatory amino acid transporters (EAATs) were measured by western blot. Microdialysis and high-performance liquid chromatography (HPLC) were used to detect hippocampal glutamate concentrations. We found that the expression of EAAT2 and EAAT3 were obviously downregulated, and extracellular concentrations of glutamate were significantly increased in the hippocampi of depressive-like rats. Ketamine (10, 25, and 50mg/kg) upregulated the expression of EAAT2 and EAAT3, decreased the hippocampal concentration of extracellular glutamate, and alleviated the rats' depressive-like behavior. The antidepressant effect of ketamine may be linked to the regulation of EAAT expression and the enhancement of glutamate uptake in the hippocampus of depressive-like rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Stress-induced endocrine response and anxiety: the effects of comfort food in rats.

PubMed

Ortolani, Daniela; Garcia, Márcia Carvalho; Melo-Thomas, Liana; Spadari-Bratfisch, Regina Celia

2014-05-01

The long-term effects of comfort food in an anxiogenic model of stress have yet to be analyzed. Here, we evaluated behavioral, endocrine and metabolic parameters in rats submitted or not to chronic unpredictable mild stress (CUMS), with access to commercial chow alone or to commercial chow and comfort food. Stress did not alter the preference for comfort food but decreased food intake. In the elevated plus-maze (EPM) test, stressed rats were less likely to enter/remain in the open arms, as well as being more likely to enter/remain in the closed arms, than were control rats, both conditions being more pronounced in the rats given access to comfort food. In the open field test, stress decreased the time spent in the centre, independent of diet; neither stress nor diet affected the number of crossing, rearing or grooming episodes. The stress-induced increase in serum corticosterone was attenuated in rats given access to comfort food. Serum concentration of triglycerides were unaffected by stress or diet, although access to comfort food increased total cholesterol and glucose. It is concluded that CUMS has an anorexigenic effect. Chronic stress and comfort food ingestion induced an anxiogenic profile although comfort food attenuated the endocrine stress response. The present data indicate that the combination of stress and access to comfort food, common aspects of modern life, may constitute a link among stress, feeding behavior and anxiety.

Mesoporous hydroxyapatite as a carrier of olanzapine for long-acting antidepression treatment in rats with induced depression.

PubMed

Shyong, Yan-Jye; Wang, Mao-Hsien; Kuo, Li-Wei; Su, Chang-Fu; Kuo, Wei-Ting; Chang, Kuo-Chi; Lin, Feng-Huei

2017-06-10

An antidepressant carrier, mesoporous hydroxyapatite olanzapine (mesoHAP-OLZ), was designed to maintain 3weeks of constant medication release. The carrier was intramuscularly (IM) injected, where cellular activity played a role in achieving the goal of constant release. The efficiency of the treatment was evaluated from 3 perspectives in in vivo studies: locomotor activities, biomarkers, and learning and memory ability. MesoHAP-OLZ can increase the locomotor activity in rats with induced depression determined by open field test (OFT) and forced swim test (FST). Serotonin (5-HT), one of the most important biomarker in depression can also be increased by mesoHAP-OLZ, leading to increased hippocampus activity as measured by functional magnetic resonance imaging (fMRI). MesoHAP-OLZ can also improve learning and memory ability in rats with induced depression during Morris water maze (MWM) test. Our findings further show that mesoHAP-OLZ can provide long-term drug release with a single IM injection, helping to solve the problem of non-adherent medication intake that often occurs in antidepressant therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Applications of Animal Research in the Behavioral Sciences: Effects of Chronic Exercise on Emotionality in Rats.

ERIC Educational Resources Information Center

Tharp, Gerald D.

The psychological effects of exercise training are difficult to study in humans, but analogous emotionality changes in animals can be studied using simple measurements employed in emergence and open-field tests. The basis of these tests is that animals that are more emotional are more fearful when placed in a novel situation and will exhibit less…

Rat electropharmacograms of the flavonoids rutin and quercetin in comparison to those of moclobemide and clinically used reference drugs suggest antidepressive and/or neuroprotective action.

PubMed

Dimpfel, Wilfried

2009-04-01

In order to be able to test single constituents of herbal plant extracts with respect to possible clinical usefulness, the model of local field potential analysis leading to the so-called electropharmacogram has been successfully used in rats to classify the effects of theanine and theogallin in the past. The present investigation aims at the prediction of efficacy and possible mechanisms of action of rutin and quercetin. Adult rats (day-night converted) were instrumented with four bipolar concentric electrodes into the frontal cortex, hippocampus, striatum and reticular formation. Field potentials were recorded during a pre-drug reference period of 45 min followed by oral administration of the particular test compound and 4h recording thereafter. Data were transmitted wirelessly to the computer for spectral frequency analysis. Rutin (5-80 mg/kg) as well as quercetin (5-40 mg/kg orally) produced similar electropharmacograms with dose dependent decreases of spectral alpha2 and beta1 frequencies within all brain areas. Peak effects were reached 4h after administration. The pattern of changes approached that obtained after 2.5mg/kg of moclobemide during the first hour as revealed by discriminant analysis in comparison to a large matrix of other drugs with known clinical indications. Data suggest antidepressant capabilities for rutin and quercetin with inhibition of monoamino oxidase at least as part of the mechanism of action. Both compounds should be tested clinically in patients with symptoms of depression.

Antidepressant-like effects of a cocoa polyphenolic extract in Wistar-Unilever rats.

PubMed

Messaoudi, Michaël; Bisson, Jean-François; Nejdi, Amine; Rozan, Pascale; Javelot, Hervé

2008-12-01

Depression is a major public health problem affecting about 12% of the world population. Drugs exist but they have many side effects. In the last few years, natural substances (e.g. flavonoids) have been tested to cure such disorders. Cocoa polyphenolic extract is a complex compound prepared from non-roasted cocoa beans containing high levels of flavonoids. The antidepressant-like effect of cocoa polyphenolic extract was evaluated using the forced swimming test in rats. Cocoa polyphenolic extract significantly reduced the duration of immobility at both doses of 24 mg/kg/14 days and 48 mg/kg/14 days, although no change of motor dysfunction was observed with the two doses tested in the open field. The results of the forced swimming test after a subchronic treatment and after an additional locomotor activity test confirm the assumption that the antidepressant-like effect of cocoa polyphenolic extract in the forced swimming test model is specific. Further, it can be speculated that this effect might be related to its content of active polyphenols.

Perinatal exposure to the selective serotonin reuptake inhibitor citalopram alters spatial learning and memory, anxiety, depression, and startle in Sprague-Dawley rats.

PubMed

Sprowles, Jenna L N; Hufgard, Jillian R; Gutierrez, Arnold; Bailey, Rebecca A; Jablonski, Sarah A; Williams, Michael T; Vorhees, Charles V

2016-11-01

Selective serotonin reuptake inhibitors (SSRIs) block the serotonin (5-HT) reuptake transporter (SERT) and increase synaptic 5-HT. 5-HT is also important in brain development; hence when SSRIs are taken during pregnancy there exists the potential for these drugs to affect CNS ontogeny. Prenatal SSRI exposure has been associated with an increased prevalence of autism spectrum disorder (ASD), and peripheral 5-HT is elevated in some ASD patients. Perinatal SSRI exposure in rodents has been associated with increased depression and anxiety-like behavior, decreased sociability, and impaired learning in the offspring, behaviors often seen in ASD. The present study investigated whether perinatal exposure to citalopram causes persistent neurobehavioral effects. Gravid Sprague-Dawley rats were assigned to two groups and subcutaneously injected twice per day with citalopram (10mg/kg; Cit) or saline (Sal) 6h apart on embryonic day (E)6-21, and then drug was given directly to the pups after delivery from postnatal day (P)1-20. Starting on P60, one male/female from each litter was tested in the Cincinnati water maze (CWM) and open-field before and after MK-801. A second pair from each litter was tested in the Morris water maze (MWM) and open-field before and after (+)-amphetamine. A third pair was tested as follows: elevated zero-maze, open-field, marble burying, prepulse inhibition of acoustic startle, social preference, and forced swim. Cit-exposed rats were impaired in the MWM during acquisition and probe, but not during reversal, shift, or cued trials. Cit-exposed rats also showed increased marble burying, decreased time in the center of the open-field, decreased latency to immobility in forced swim, and increased acoustic startle across prepulse intensities with no effects on CWM. The results are consistent with citalopram inducing several ASD-like effects. The findings add to concerns about use of SSRIs during pregnancy. Further research on different classes of antidepressants, dose-effect relationships, timing of exposure periods, and mechanisms for these effects are needed. It is also important to balance the effects described here against the effects of the disorders for which the drugs are given. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

The traverse planning process for D-RATS 2010

NASA Astrophysics Data System (ADS)

Hörz, Friedrich; Lofgren, Gary E.; Gruener, John E.; Eppler, Dean B.; Skinner, James A.; Fortezzo, Corey M.; Graf, Jodi S.; Bluethmann, William J.; Seibert, Marc A.; Bell, Ernest R.

2013-10-01

This report describes the traverse planning process for the Desert Research and Technology Studies (D-RATS) 2010 field simulation of a conceptual 14-day planetary mission. This activity took place between August 23 and September 17, 2010 in the San Francisco Volcanic Field, Arizona. It focused on the utilization of two pressurized rovers and a ground-based communication system, as well as on the development of mission operation concepts for long duration, dual-rover missions. The early planning process began some 12 months prior to the actual field tests and defined the first order engineering-, flight operations, and science objectives. The detailed implementation and refinement of these objectives took place over the ensuing 10 months, resulting in a large number of technical and operational constraints that affected the actual traverse route or the cumulative Extravehicular Activity (EVA) time available for detailed field observations. The science planning proceeded from the generation of photogeologic maps of the test area, to the establishment of prioritized science objectives and associated candidate sites for detailed field exploration. The combination of operational constraints and science objectives resulted in the final design of traverse routes and time lines for each of the 24 traverses needed to support 12 field days by two rovers. Examples of daily traverses will be given that will hopefully illustrate that the design of long duration, long distance planetary traverses is a highly interdisciplinary and time-consuming collaboration between diverse engineers, flight operations personnel, human factors interests, and planetary scientists.

Factors enhancing the migration and the homing of mesenchymal stem cells in experimentally induced cardiotoxicity in rats.

PubMed

A Soliman, Nabil; Abd-Allah, Somia H; Hussein, Samia; Alaa Eldeen, Muhammad

2017-03-01

Doxorubicin is an effective anti-neoplastic drug but its use is limited by its cardiotoxicity. Administration of mesenchymal stem cells (MSCs) for the management of cardiotoxicity was with poor myocardial homing capacity. With the aim of developing novel techniques to improve the migration of MSCs, we tested whether valproate and electric fields (EFs) direct the migration of MSCs towards the damaged myocardium. The study included five groups of female albino rats. The first group included 10 healthy rats as normal control group. The remaining 40 female rats received doxorubicin for induction of acute cardiotoxicity. Four rats were sacrificed for histopathological confirmation of cardiotoxicity. The remaining rats were equally divided into subsequent four groups. The second group included nine rats that did not receive further treatment (positive control group). The third group included nine rats which received intravenous bone marrow derived mesenchymal stem cells (BM-MSCs) after cardiotoxicity induction. The fourth group included nine rats which received BM-MSCs plus sodium valporate after cardiotoxicity induction. The fifth group included nine rats which received BM-MSCs plus sodium valporate after cardiotoxicity induction and were exposed to an electrical stimulation (ES). Blood samples were taken from all groups at the end of the study to estimate creatine kinase-MB (CK-MB), aspartate transaminase (AST) and lactate dehydrogenase (LDH). Heart tissues from all rats were used for RNA extraction for assessment of sry gene expression. Homing was tested by PKH26 fluorescence in myocardial tissue sections and by sry gene expression. The best biochemical and histopathological improvement in cardiotoxicity was demonstrated in group 5 (rats that received ES and valporate with MSCs). We concluded that EFs and sodium valproate enhance homing ability of MSCs towards the damaged myocardium in doxorubicin induced carditoxicity model. © 2017 IUBMB Life, 69(3):162-169, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Evaluation of inflammatory biomarkers associated with oxidative stress and histological assessment of magnetic therapy on experimental myopathy in rats.

PubMed

Vignola, María Belén; Dávila, Soledad; Cremonezzi, David; Simes, Juan C; Palma, José A; Campana, Vilma R

2012-12-01

The effect of pulsed electromagnetic field (PEMF) therapy, also called magnetic therapy, upon inflammatory biomarkers associated with oxidative stress plasma fibrinogen, nitric oxide (NO), L-citrulline, carbonyl groups, and superoxide dismutase (SOD) was evaluated through histological assessment, in rats with experimental myopathy. The groups studied were: (A) control (intact rats that received PEMF sham exposures); (B) rats with myopathy and sacrificed 24 h later; (C) rats with myopathy; (D) rats with myopathy and treated with PEMF; and (E) intact rats treated with PEMF. Groups A, C, D, and E were sacrificed 8 days later. Myopathy was induced by injecting 50 μl of 1% carrageenan λ (type IV) once sub-plantar. Treatment was carried out with PEMF emitting equipment with two flat solenoid disks for 8 consecutive days in groups D and E, at 20 mT and 50 Hz for 30 min/day/rat. The biomarkers were determined by spectrophotometry. The muscles (5/8) were stained with Hematoxylin-Eosin and examined by optic microscopy. Quantitative variables were statistically analyzed by the Fisher test, and categorical applying Pearson's Chi Squared test at p < 0.05 for all cases. In Groups B and C, the biomarkers were significantly increased compared to A, D, and E groups: fibrinogen (p < 0.001); NO, L-citrulline and carbonyl groups (p < 0.05); SOD (p < 0.01) as well as the percentage of area with inflammatory infiltration (p < 0.001). PEMF caused decreased levels of fibrinogen, L-citrulline, NO, SOD, and carbonyl groups and significant muscle recovery in rats with experimental myopathies.

Exposure to activity-based anorexia impairs contextual learning in weight-restored rats without affecting spatial learning, taste, anxiety, or dietary-fat preference.

PubMed

Boersma, Gretha J; Treesukosol, Yada; Cordner, Zachary A; Kastelein, Anneke; Choi, Pique; Moran, Timothy H; Tamashiro, Kellie L

2016-02-01

Relapse rates are high amongst cases of anorexia nervosa (AN) suggesting that some alterations induced by AN may remain after weight restoration. To study the consequences of AN without confounds of environmental variability, a rodent model of activity-based anorexia (ABA) can be employed. We hypothesized that exposure to ABA during adolescence may have long-term consequences in taste function, cognition, and anxiety-like behavior after weight restoration. To test this hypothesis, we exposed adolescent female rats to ABA (1.5 h food access, combined with voluntary running wheel access) and compared their behavior to that of control rats after weight restoration was achieved. The rats were tested for learning/memory, anxiety, food preference, and taste in a set of behavioral tests performed during the light period. Our data show that ABA exposure leads to reduced performance during the novel object recognition task, a test for contextual learning, without altering performance in the novel place recognition task or the Barnes maze, both tasks that test spatial learning. Furthermore, we do not observe alterations in unconditioned lick responses to sucrose nor quinine (described by humans as "sweet" and "bitter," respectively). Nor Do we find alterations in anxiety-like behavior during an elevated plus maze or an open field test. Finally, preference for a diet high in fat is not altered. Overall, our data suggest that ABA exposure during adolescence impairs contextual learning in adulthood without altering spatial leaning, taste, anxiety, or fat preference. © 2015 Wiley Periodicals, Inc.

Repeated Acute Oral Exposure to Cannabis sativa Impaired Neurocognitive Behaviours and Cortico-hippocampal Architectonics in Wistar Rats.

PubMed

Imam, A; Ajao, M S; Akinola, O B; Ajibola, M I; Ibrahim, A; Amin, A; Abdulmajeed, W I; Lawal, Z A; Ali-Oluwafuyi, A

2017-03-06

The most abused illicit drug in both the developing and the developed world is Cannabis disposing users to varying forms of personality disorders. However, the effects of cannabis on cortico-hippocampal architecture and cognitive behaviours still remain elusive.  The present study investigated the neuro-cognitive implications of oral cannabis use in rats. Eighteen adult Wistar rats were randomly grouped to three. Saline was administered to the control rats, cannabis (20 mg/kg) to the experimental group I, while Scopolamine (1 mg/kg. ip) was administered to the last group as a standard measure for the cannabis induced cognitive impairment. All treatments lasted for seven consecutive days. Open Field Test (OFT) was used to assess locomotor activities, Elevated Plus Maze (EPM) for anxiety-like behaviour, and Y maze paradigm for spatial memory and data subjected to ANOVA and T test respectively. Thereafter, rats were sacrificed and brains removed for histopathological studies. Cannabis significantly reduced rearing frequencies in the OFT and EPM, and increased freezing period in the OFT. It also reduced percentage alternation similar to scopolamine in the Y maze, and these effects were coupled with alterations in the cortico-hippocampal neuronal architectures. These results point to the detrimental impacts of cannabis on cortico-hippocampal neuronal architecture and morphology, and consequently cognitive deficits.

Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats

PubMed Central

da Silva, Fernando B. R.; Cunha, Polyane A.; Ribera, Paula C.; Barros, Mayara A.; Cartágenes, Sabrina C.; Fernandes, Luanna M. P.; Teixeira, Francisco B.; Fontes-Júnior, Enéas A.; Prediger, Rui D.; Lima, Rafael R.; Maia, Cristiane S. F.

2018-01-01

Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures’ morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF), pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats.

PubMed

da Silva, Fernando B R; Cunha, Polyane A; Ribera, Paula C; Barros, Mayara A; Cartágenes, Sabrina C; Fernandes, Luanna M P; Teixeira, Francisco B; Fontes-Júnior, Enéas A; Prediger, Rui D; Lima, Rafael R; Maia, Cristiane S F

2018-01-01

Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures' morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF), pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

NTP Studies of Magnetic Field Promotion (DMBA Initiation) in Female Sprague-Dawley Rats (Whole-body Exposure/Gavage Studies).

PubMed

1999-08-01

Electric and magnetic fields are associated with the production, transmission, and use of electricity; thus, the potential for human exposure is high. These elec-tric and magnetic fields are predominantly of low fre-quency (60 Hz in the United States and 50 Hz in Europe) and generally of low intensity. Because some epidemiology studies and initiation/promotion studies in rats have suggested a potential for increased breast cancer rates with increasing magnetic field exposure, the ability of 50- and 60-Hz magnetic fields to pro-mote mammary gland tumors initiated by the administration of 7,12-dimethylbenz(a)anthracene (DMBA) was examined in female Sprague-Dawley rats in 13- and 26-week whole-body exposure studies. Additional animals were evaluated for changes in pineal gland and serum melatonin concentrations. FIRST 13-WEEK STUDY: Groups of 100 female Sprague-Dawley rats were ad-ministered 20 mg DMBA (four weekly gavage doses of 5 mg in sesame oil) and exposed to 1 G 50-Hz, 5 G 50-Hz, or 1 G 60-Hz magnetic fields for 18.5 hours per day, 7 days per week, for 13 weeks. A group of 100 rats administered 20 mg DMBA served as DMBA controls. A group of 100 vehicle control rats was administered only sesame oil on the same schedule. Additional groups of 10 rats receiving similar treatment were evaluated for pineal gland and serum melatonin concentrations at 4, 8, or 12 weeks. All vehicle control rats survived to the end of the study. Of the animals administered 20 mg DMBA, 6 rats in the DMBA control group, 13 in the DMBA/1 G 50-Hz group, eight in the DMBA/5 G 50-Hz group, and five in the DMBA/1 G 60-Hz group died or were removed from the study prior to the final necropsy. Final mean body weights and body weight gains of the DMBA/1 G 50-Hz and DMBA/1 G 60-Hz groups and the mean body weight gain of the DMBA/5 G 50-Hz group were slightly greater than those of the DMBA control group. Clinical findings including torso masses and ulcers (on the mammary masses) were attributed to DMBA administration. The numbers of palpable mammary gland tumors, tumor sizes, and total tumor areas in DMBA/magnetic field groups were similar to those in the DMBA control group. Relative to the DMBA control group, exposure to magnetic fields did not significantly affect overall incidences of mammary gland neoplasms or nonneoplastic lesions in the DMBA/magnetic field groups. SECOND 13-WEEK STUDY: Groups of 100 female Sprague-Dawley rats were ad-ministered 8 mg DMBA (four weekly gavage doses of 2 mg in sesame oil) and exposed to 1 G 50-Hz or 5 G 50-Hz magnetic fields for 18.5 hours per day, 7 days per week, for 13 weeks. A group of 100 female rats administered 8 mg DMBA served as DMBA controls. Additional groups of 10 rats receiving similar treatment were evaluated for pineal gland and serum melatonin concentrations at 4, 8, or 12 weeks. Except for one rat in the DMBA/5 G 50-Hz group, all rats survived until the end of the study. Final mean body weights of DMBA/magnetic field groups were similar to those of the DMBA control group. Clinical findings including torso masses and ulcers were attributed to DMBA administration. The numbers of palpable mammary gland tumors, tumor sizes, and total tumor areas in DMBA/magnetic field groups were similar to those in the DMBA control group. Relative to the DMBA control group, exposure to magnetic fields did not significantly affect overall incidences of mammary gland neoplasms or nonneoplastic lesions in the DMBA/magnetic field groups. 26-WEEK STUDY: Groups of 100 female Sprague-Dawley rats were administered 10 mg DMBA (in sesame oil) by gavage followed by exposure to 1 G 50-Hz, 5 G 50-Hz, or 1 G 60-Hz magnetic fields for 18.5 hours per day, 7 days per week, for 26 weeks. A group of 100 female rats administered 10 mg DMBA served as DMBA controls. Another 100 vehicle control rats were administered only sesame oil. Additional groups of 10 rats receiving similar treatment were evaluated for pineal gland and serum melatonin concentrations at 4, 8, or 12 weeks. All rats in the vehicle control group survived until the end of the study. Twelve rats in the DMBA control group, 15 in the DMBA/1 G 50-Hz group, 9 in the DMBA/5 G 50-Hz group, and six in the DMBA/1 G 60-Hz group died or were removed during the study. The final mean body weights and body weight gains of the DMBA/1 G 50-Hz and DMBA/5 G 50-Hz groups were significantly greater than those of the DMBA control group. Clinical findings including torso masses, abscesses, and ulcers were attributed to DMBA administration. The pineal gland melatonin concentrations of DMBA/5 G 50-Hz and DMBA/1 G 60-Hz rats were significantly greater than that of the DMBA controls at week 12; however, these data were highly variable between individual animals within each group. The numbers of palpable mammary gland tumors, tumor sizes, and total tumor areas in DMBA/magnetic field groups were similar to those in the DMBA controls. The incidences of mammary gland carci-noma (including multiple) in the DMBA/1 G 60-Hz group were significantly decreased relative to the DMBA control group. CONCLUSIONS: In an initiation/promotion study in which female Sprague-Dawley rats were initiated by four weekly doses of 5 mg DMBA per rat beginning at 50 days of age and exposed to 50-Hz magnetic fields at 1 or 5 G field intensities or to 1 G 60-Hz magnetic fields for 13 weeks, there was no evidence that magnetic fields promoted the development of mammary gland neoplasms. The prevalence and multiplicity of mammary gland carcinomas in all DMBA groups limited the ability of this assay to detect a promoting effect of magnetic fields. In an initiation/promotion study in which female Sprague-Dawley rats were initiated by four weekly doses of 2 mg DMBA per rat beginning at 50 days of age and exposed to 50-Hz magnetic fields at 1 or 5 G field intensities for 13 weeks, there was no evidence that magnetic fields promoted the development of mammary gland neoplasms. In an initiation/promotion study in which female Sprague-Dawley rats were initiated by a single 10 mg DMBA dose at 50 days of age and then exposed to 50-Hz magnetic fields at 1 or 5 G field intensities or to 1 G 60-Hz magnetic fields for 26 weeks, there was no evidence that magnetic fields promoted the development of mammary gland neoplasms.

NASA Desert RATS 2010: Preliminary Results for Science Operations Conducted in the San Francisco Volcanic Field, Arizona

NASA Technical Reports Server (NTRS)

Gruener, J. E.; Lofgren, G. E.; Bluethmann, W. J.; Bell, E. R.

2011-01-01

The National Aeronautics and Space Administration (NASA) is working with international partners to develop the space architectures and mission plans necessary for human spaceflight beyond earth orbit. These mission plans include the exploration of planetary surfaces with significant gravity fields. The Apollo missions to the Moon demonstrated conclusively that surface mobility is a key asset that improves the efficiency of human explorers on a planetary surface. NASA's Desert Research and Technology Studies (Desert RATS) is a multi-year series tests of hardware and operations carried out annually in the high desert of Arizona. Conducted since 1998, these activities are designed to exercise planetary surface hardware and operations in relatively harsh climatic conditions where long-distance, multi-day roving is achievable

Effects of aerosol-vapor JP-8 jet fuel on the functional observational battery, and learning and memory in the rat.

PubMed

Baldwin, C M; Houston, F P; Podgornik, M N; Young, R S; Barnes, C A; Witten, M L

2001-01-01

To determine whether JP-8 jet fuel affects parameters of the Functional Observational Battery (FOB), visual discrimination, or spatial learning and memory, the authors exposed groups of male Fischer Brown Norway hybrid rats for 28 d to aerosol/vapor-delivered JP-8, or to JP-8 followed by 15 min of aerosolized substance P analogue, or to sham-confined fresh room air. Behavioral testing was accomplished with the U.S. Environmental Protection Agency's Functional Observational Battery. The authors used the Morris swim task to test visual and spatial learning and memory testing. The spatial test included examination of memory for the original target location following 15 d of JP-8 exposure, as well as a 3-d new target location learning paradigm implemented the day that followed the final day of exposure. Only JP-8 exposed animals had significant weight loss by the 2nd week of exposure compared with JP-8 with substance P and control rats; this finding compares with those of prior studies of JP-8 jet fuel. Rats exposed to JP-8 with or without substance P exhibited significantly greater rearing and less grooming behavior over time than did controls during Functional Observational Battery open-field testing. Exposed rats also swam significantly faster than controls during the new target location training and testing, thus supporting the increased activity noted during Functional Observational Battery testing. There were no significant differences between the exposed and control groups' performances during acquisition, retention, or learning of the new platform location in either the visual discrimination or spatial version of the Morris swim task. The data suggest that although visual discrimination and spatial learning and memory were not disrupted by JP-8 exposure, arousal indices and activity measures were distinctly different in these animals.

Learning and memory in streptozotocin-induced diabetic rats in a novel spatial/object discrimination task.

PubMed

Popoviç, M; Biessels, G J; Isaacson, R L; Gispen, W H

2001-08-01

Diabetes mellitus is associated with disturbances of cognitive functioning. The aim of this study was to examine cognitive functioning in diabetic rats using the 'Can test', a novel spatial/object learning and memory task, without the use of aversive stimuli. Rats were trained to select a single rewarded can from seven cans. Mild water deprivation provided the motivation to obtain the reward (0.3 ml of water). After 5 days of baseline training, in which the rewarded can was marked by its surface and position in an open field, the animals were divided into two groups. Diabetes was induced in one group, by an intravenous injection of streptozotocin. Retention of baseline training was tested at 2-weekly intervals for 10 weeks. Next, two adapted versions of the task were used, with 4 days of training in each version. The rewarded can was a soft-drink can with coloured print. In a 'simple visual task' the soft-drink can was placed among six white cans, whereas in a 'complex visual task' it was placed among six soft-drink cans from different brands with distinct prints. In diabetic rats the number of correct responses was lower and number of reference and working memory errors higher than in controls in the various versions of the test. Switches between tasks and increases in task complexity accentuated the performance deficits, which may reflect an inability of diabetic rats to adapt behavioural strategies to the demands of the tasks.

Protective effect of vinpocetine against neurotoxicity of manganese in adult male rats.

PubMed

Nadeem, Rania I; Ahmed, Hebatalla I; El-Sayeh, Bahia M

2018-04-18

Manganese (Mn) is required for many essential biological processes as well as in the development and functioning of the brain. Extensive accumulation of Mn in the brain may cause central nervous system dysfunction known as manganism, a motor disorder associated with cognitive and neuropsychiatric deficits similar to parkinsonism. Vinpocetine, a synthetic derivative of the alkaloid vincamine, is used to improve the cognitive function in cerebrovascular diseases. It possesses antioxidant and antiinflammatory properties. The present work was designed to explore the potential neuroprotective mechanisms exerted by vinpocetine in the Mn-induced neurotoxicity in rats. Rats were allocated into four groups. First group was given saline. The other three groups were given MnCl 2 ; two of them were treated with either L-dopa, the gold standard antiparkinsonian drug, or vinpocetine. Rats receiving MnCl 2 exhibited lengthened catalepsy duration in the grid and bar tests, motor impairment in the open-field test and short-term memory deficit in the Y-maze test. Additionally, histological examination revealed structural alterations and degeneration in different brain regions. Besides, striatal monoamines and mitochondrial complex I contents were declined, apoptotic biomarker caspase-3 expression and acetylcholinesterase activity were elevated. Moreover, oxidative stress and inflammation were detected in the striata. L-dopa or vinpocetine exerted protective effects against MnCl 2 -induced neurotoxicity. It could be hypothesized that modulation of monoamines, upregulation of mitochondrial complex I, antioxidant, antiinflammatory, and antiapoptotic activities are significant mechanisms underlying the neuroprotective effect of vinpocetine in the Mn-induced neurotoxicity model in rats.

A strong static-magnetic field alters operant responding by rats.

PubMed

Nakagawa, M; Matsuda, Y

1988-01-01

Forty male rats of the Wistar ST strain were trained and observed for Sidman avoidance (SA) for 7 weeks or for discriminative avoidance (DA) for 14 weeks to determine the effects of exposure to a strong static-magnetic field. Before avoidance conditioning was completed, rats in the SA group were exposed to the static field at 0.6 T, 16 h/day for 4 days during the fifth week, and those in the DA group were exposed for 6 h/day for 4 days during the seventh week. In the SA conditioning, frequency of lever-pressing by exposed rats gradually decreased during 1 week of exposure and stayed low for at least 2 weeks after exposure. Frequencies of electric shocks received by the rats increased dramatically during the second day of exposure and consistently stayed higher than those of control rats. In the DA condition, exposed rats responded at lower rates than did control rats throughout the observation period. They received more shocks during the 2 weeks following exposure. The data indicate that performance of avoidance responses was inhibited by a comparatively long exposure to a strong magnetic field.

Exposure to 900 MHz electromagnetic fields activates the mkp-1/ERK pathway and causes blood-brain barrier damage and cognitive impairment in rats.

PubMed

Tang, Jun; Zhang, Yuan; Yang, Liming; Chen, Qianwei; Tan, Liang; Zuo, Shilun; Feng, Hua; Chen, Zhi; Zhu, Gang

2015-03-19

With the rapid increase in the number of mobile phone users, the potential adverse effects of the electromagnetic field radiation emitted by a mobile phone has become a serious concern. This study demonstrated, for the first time, the blood-brain barrier and cognitive changes in rats exposed to 900 MHz electromagnetic field (EMF) and aims to elucidate the potential molecular pathway underlying these changes. A total of 108 male Sprague-Dawley rats were exposed to a 900 MHz, 1 mW/cm(2) EMF or sham (unexposed) for 14 or 28 days (3h per day). The specific energy absorption rate (SAR) varied between 0.016 (whole body) and 2 W/kg (locally in the head). In addition, the Morris water maze test was used to examine spatial memory performance determination. Morphological changes were investigated by examining ultrastructural changes in the hippocampus and cortex, and the Evans Blue assay was used to assess blood brain barrier (BBB) damage. Immunostaining was performed to identify heme oxygenase-1 (HO-1)-positive neurons and albumin extravasation detection. Western blot was used to determine HO-1 expression, phosphorylated ERK expression and the upstream mediator, mkp-1 expression. We found that the frequency of crossing platforms and the percentage of time spent in the target quadrant were lower in rats exposed to EMF for 28 days than in rats exposed to EMF for 14 days and unexposed rats. Moreover, 28 days of EMF exposure induced cellular edema and neuronal cell organelle degeneration in the rat. In addition, damaged BBB permeability, which resulted in albumin and HO-1 extravasation were observed in the hippocampus and cortex. Thus, for the first time, we found that EMF exposure for 28 days induced the expression of mkp-1, resulting in ERK dephosphorylation. Taken together, these results demonstrated that exposure to 900 MHz EMF radiation for 28 days can significantly impair spatial memory and damage BBB permeability in rat by activating the mkp-1/ERK pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of the brain-penetrant and selective 5-HT6 receptor antagonist SB-399885 in animal models of anxiety and depression.

PubMed

Wesołowska, Anna; Nikiforuk, Agnieszka

2007-04-01

The effects of a selective 5-HT(6) receptor antagonist, SB-399885 (N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide), were evaluated in behavioural tests sensitive to clinically effective anxiolytic- and antidepressant-compounds using diazepam and imipramine as reference drugs. In the Vogel conflict drinking test in rats, SB-399885 (1-3mg/kg i.p.) caused an anxiolytic-like activity comparable to that of diazepam (2.5-5mg/kg i.p.). An anxiolytic-like effect was also seen in the elevated plus-maze test in rats, where SB-399885 (0.3-3mg/kg i.p.) was slightly weaker than diazepam (2.5-5mg/kg i.p.). In the four-plate test in mice, SB-399885 (3-20mg/kg i.p.) showed an anxiolytic-like effect which was weaker than that produced by diazepam (2.5-5mg/kg i.p.). In the forced swim test in rats, SB-399885 (10mg/kg i.p.) significantly shortened the immobility time and the effect was stronger than that of imipramine (30mg/kg i.p.). In the forced swim test in mice, SB-399885 (20-30mg/kg i.p.) had an anti-immobility action, comparable to imipramine (30mg/kg i.p.) and also in the tail suspension test in mice, SB-399885 (10-30mg/kg i.p.) had an antidepressant-like effect, though was weaker than imipramine (10-20mg/kg i.p.). The tested 5-HT(6) antagonist (3-20mg/kg i.p.) shortened the walking time of rats in the open field test and, at a dose of 30mg/kg i.p. reduced the locomotor activity of mice. SB-399885 (in doses up to 30mg/kg i.p.) did not affect motor coordination in mice and rats tested in the rota-rod test. Such data indicate that the selective 5-HT(6) receptor antagonist SB-399885had specific effects, indicative of this compound's anxiolytic and antidepressant potential.

Core temperature is regulated, although at a lower temperature, in rats exposed to hypergravic fields

NASA Technical Reports Server (NTRS)

Monson, C. B.; Horowitz, J. M.; Horwitz, B. A.

1988-01-01

1. In rats acclimated to 23 degrees C (RT rats) or 5 degrees C (CA rats), core temperature (Tc), tail temperature (Tt) and oxygen consumption (VO2) were measured during exposure to a hypergravic field. 2. Rats were exposed for 5.5 h to a 3 g field while ambient temperature (Ta) was varied. For the first 2 h, Ta was 25 degrees C; then Ta was raised to 34 degrees C for 1.5 h. During this period of warm exposure, Tc increased 4 degrees C in both RT and CA rats. Finally, Ta was returned to 25 degrees C for 2 h, and Tc decreased toward the levels measured prior to warm exposure. 3. In a second experiment at 3 g, RT and CA rats were exposed to cold (12 degrees C) after two hours at 25 degrees C. During the one hour cold exposure, Tc fell 1.5 degrees C in RT and 0.5 degree C in CA rats. After cold exposure, when ambient temperature was again 25 degrees C, Tc of RT and CA rats returned toward the levels measured prior to the thermal disturbance. 4. Rats appear to regulate their temperature, albeit at a lower level, in a 3 g field.

The functional link between tail-pinch-induced food intake and emotionality and its possible role in stress coping in rats.

PubMed

Aso-Someya, Nami; Narikiyo, Kimiya; Masuda, Akira; Aou, Shuji

2018-02-08

Tail pinch facilitates eating in rats. We investigated an unidentified link between tail-pinch-induced eating behavior and individual emotionality in male Sprague-Dawley rats. Anxiety-like behavior was assessed on the elevated plus maze (EPM) and in the open field test (OFT). Tail-pinch-induced eating was observed as follows: After a 30-min habituation period, the tail pinch was applied for 5 min, followed by a 30-min recovery period. During the habituation and recovery periods, rats were allowed to access food ad libitum. During the recovery period, 14 of 24 rats ate more food than during the habituation period. Thus, we named them "high responders" and the others as "low responders". The food intake was significantly greater, while the times spent in the open arms in the EPM and in the center area in the OFT were significantly shorter in high responders than in low responders. This result suggests that the rats consuming more food after mild stress have higher anxiety.

Speech training alters consonant and vowel responses in multiple auditory cortex fields

PubMed Central

Engineer, Crystal T.; Rahebi, Kimiya C.; Buell, Elizabeth P.; Fink, Melyssa K.; Kilgard, Michael P.

2015-01-01

Speech sounds evoke unique neural activity patterns in primary auditory cortex (A1). Extensive speech sound discrimination training alters A1 responses. While the neighboring auditory cortical fields each contain information about speech sound identity, each field processes speech sounds differently. We hypothesized that while all fields would exhibit training-induced plasticity following speech training, there would be unique differences in how each field changes. In this study, rats were trained to discriminate speech sounds by consonant or vowel in quiet and in varying levels of background speech-shaped noise. Local field potential and multiunit responses were recorded from four auditory cortex fields in rats that had received 10 weeks of speech discrimination training. Our results reveal that training alters speech evoked responses in each of the auditory fields tested. The neural response to consonants was significantly stronger in anterior auditory field (AAF) and A1 following speech training. The neural response to vowels following speech training was significantly weaker in ventral auditory field (VAF) and posterior auditory field (PAF). This differential plasticity of consonant and vowel sound responses may result from the greater paired pulse depression, expanded low frequency tuning, reduced frequency selectivity, and lower tone thresholds, which occurred across the four auditory fields. These findings suggest that alterations in the distributed processing of behaviorally relevant sounds may contribute to robust speech discrimination. PMID:25827927

[Free radical modification of proteins in brain structure of Sprague-Dawley rats and some behaviour indicators after prenatal stress].

PubMed

V'iushina, A V; Pritvorova, A V; Flerov, M A

2012-08-01

We studied the influence of late prenatal stress on free radical oxidation processes in Sprague-Dawley rats cortex, striatum, hippocampus, hypothalamus proteins. It was shown that after prenatal stress most changes were observed in hypothalamus and hippocampus. It was shown that in hypothalamus spontaneous oxidation level increased, but level of induced oxidation decreased, the opposite changes were found in hippocampus. Simultaneously minor changes of protein modification were observed in cortex and striatum. It was shown that prenatal stress changed both correlation of proteins free radical oxidation in studied structures and values of these data regarding to control. In test of "open field" motor activity in rats after prenatal stress decreased and time of freezing and grooming increased; opposite, in T-labyrinth motor activity and time of grooming in rats after prenatal stress increased, but time of freezing decreased.

Altered neuronal activities in the motor cortex with impaired motor performance in adult rats observed after infusion of cerebrospinal fluid from amyotrophic lateral sclerosis patients.

PubMed

Sankaranarayani, R; Nalini, A; Rao Laxmi, T; Raju, T R

2010-01-05

Although definite evidences are available to state that, neuronal activity is a prime determinant of animal behavior, the specific relationship between local field potentials of the motor cortex after intervention with CSF from human patients and animal behavior have remained opaque. The present study has investigated whether cerebrospinal fluid from sporadic amyotrophic lateral sclerosis (sALS) patients could disrupt neuronal activity of the motor cortex, which could be associated with disturbances in the motor performance of adult rats. CSF from ALS patients (ALS-CSF) was infused into the lateral ventricle of Wistar rats. After 24h, the impact of ALS-CSF on the local field potentials (LFPs) of the motor cortex and on the motor behavior of animals were examined. The results indicate that ALS-CSF produced a bivariate distribution on the relative power values of the LFPs of the motor cortex 24h following infusion. However, the behavioral results did not show bimodality, instead showed consistent decrease in motor performance: on rotarod and grip strength meter. The neuronal activity of the motor cortex negatively correlated with the duration of ALS symptoms at the time of lumbar puncture. Although the effect of ALS-CSF was more pronounced at 24h following infusion, the changes observed in LFPs and motor performance appeared to revert to baseline values at later time points of testing. In the current study, we have shown that, ALS-CSF has the potential to perturb neuronal activity of the rat motor cortex which was associated with poor performance on motor function tests.

"Despair" induced by extinction trials in the water maze: relationship with measures of anxiety in aged and adult rats.

PubMed

Schulz, Daniela; Huston, Joseph P; Buddenberg, Tim; Topic, Bianca

2007-03-01

We have previously reported that extinction of escape behavior in the water maze due to the removal of the platform coincided with the development of behavioral "despair" in aged and adult rats, as assessed by immobility. The present study examines further predictions derived from the hypothesis that the withholding of reinforcement induces behaviors akin to depression. We tested for correlations between extinction performance and immobility, as well as between immobility and measures of anxiety in aged and adult rats. Age comparisons were also performed on these variables. Forty aged and 29 adult male Wistar rats (24 and 3 months old, respectively) were examined in the open field, black/white box and elevated-plus maze followed by 6 days of training in the water maze hidden platform task and 8 days of extinction without the platform. Indices of immobility increased over trials of extinction, with the aged showing higher levels, earlier onsets and larger slope increases of immobility than the adults. A lower resistance-to-extinction was predictive of more "despair" in both age groups. Between-group differences in the open field, black/white box and elevated-plus maze indicated that the aged showed more anxiety-like behavior than the adults and/or explored these environments less. Within the aged group, indicators of fearfulness in the three tests were predictive of higher levels of "despair". The extinction-despair model is held to provide the promise of a conceptual and empirical model of human depression that is the consequence of withdrawal of reinforcement.

Rat testicular impairment induced by electromagnetic radiation from a conventional cellular telephone and the protective effects of the antioxidants vitamins C and E

PubMed Central

Al-Damegh, Mona Abdullah

2012-01-01

OBJECTIVE: The aim of this study was to investigate the possible effects of electromagnetic radiation from conventional cellular phone use on the oxidant and antioxidant status in rat blood and testicular tissue and determine the possible protective role of vitamins C and E in preventing the detrimental effects of electromagnetic radiation on the testes. MATERIALS AND METHODS: The treatment groups were exposed to an electromagnetic field, electromagnetic field plus vitamin C (40 mg/kg/day) or electromagnetic field plus vitamin E (2.7 mg/kg/day). All groups were exposed to the same electromagnetic frequency for 15, 30, and 60 min daily for two weeks. RESULTS: There was a significant increase in the diameter of the seminiferous tubules with a disorganized seminiferous tubule sperm cycle interruption in the electromagnetism-exposed group. The serum and testicular tissue conjugated diene, lipid hydroperoxide, and catalase activities increased 3-fold, whereas the total serum and testicular tissue glutathione and glutathione peroxidase levels decreased 3-5 fold in the electromagnetism-exposed animals. CONCLUSION: Our results indicate that the adverse effect of the generated electromagnetic frequency had a negative impact on testicular architecture and enzymatic activity. This finding also indicated the possible role of vitamins C and E in mitigating the oxidative stress imposed on the testes and restoring normality to the testes. PMID:22892924

Rat testicular impairment induced by electromagnetic radiation from a conventional cellular telephone and the protective effects of the antioxidants vitamins C and E.

PubMed

Al-Damegh, Mona Abdullah

2012-07-01

The aim of this study was to investigate the possible effects of electromagnetic radiation from conventional cellular phone use on the oxidant and antioxidant status in rat blood and testicular tissue and determine the possible protective role of vitamins C and E in preventing the detrimental effects of electromagnetic radiation on the testes. The treatment groups were exposed to an electromagnetic field, electromagnetic field plus vitamin C (40 mg/kg/day) or electromagnetic field plus vitamin E (2.7 mg/kg/day). All groups were exposed to the same electromagnetic frequency for 15, 30, and 60 min daily for two weeks. There was a significant increase in the diameter of the seminiferous tubules with a disorganized seminiferous tubule sperm cycle interruption in the electromagnetism-exposed group. The serum and testicular tissue conjugated diene, lipid hydroperoxide, and catalase activities increased 3-fold, whereas the total serum and testicular tissue glutathione and glutathione peroxidase levels decreased 3-5 fold in the electromagnetism-exposed animals. Our results indicate that the adverse effect of the generated electromagnetic frequency had a negative impact on testicular architecture and enzymatic activity. This finding also indicated the possible role of vitamins C and E in mitigating the oxidative stress imposed on the testes and restoring normality to the testes.

Glucose-Dependent Insulinotropic Polypeptide Mitigates 6-OHDA-Induced Behavioral Impairments in Parkinsonian Rats

PubMed Central

Yu, Yu-Wen; Hsueh, Shih-Chang; Lai, Jing-Huei; Chen, Yen-Hua; Kang, Shuo-Jhen; Hsieh, Tsung-Hsun; Hoffer, Barry J.; Li, Yazhou; Greig, Nigel H.; Chiang, Yung-Hsiao

2018-01-01

In the present study, the effectiveness of glucose-dependent insulinotropic polypeptide (GIP) was evaluated by behavioral tests in 6-hydroxydopamine (6-OHDA) hemi-parkinsonian (PD) rats. Pharmacokinetic measurements of GIP were carried out at the same dose studied behaviorally, as well as at a lower dose used previously. GIP was delivered by subcutaneous administration (s.c.) using implanted ALZET micro-osmotic pumps. After two days of pre-treatment, male Sprague Dawley rats received a single unilateral injection of 6-OHDA into the medial forebrain bundle (MFB). The neuroprotective effects of GIP were evaluated by apomorphine-induced contralateral rotations, as well as by locomotor and anxiety-like behaviors in open-field tests. Concentrations of human active and total GIP were measured in plasma during a five-day treatment period by ELISA and were found to be within a clinically translatable range. GIP pretreatment reduced behavioral abnormalities induced by the unilateral nigrostriatal dopamine (DA) lesion produced by 6-OHDA, and thus may be a novel target for PD therapeutic development. PMID:29641447

Repeated MDMA ("Ecstasy") exposure in adolescent male rats alters temperature regulation, spontaneous motor activity, attention, and serotonin transporter binding.

PubMed

Piper, Brian J; Fraiman, Joseph B; Meyer, Jerrold S

2005-09-01

Previous research in our laboratory found that repeated exposure of adolescent rats to 3,4-methylenedioxymethamphetamine (MDMA) impaired working memory and reduced anxiety. The present experiment extended these findings by investigating the physiological, behavioral, and neurotoxic effects of a modified MDMA treatment regimen. Male Sprague-Dawley rats received 5 mg/kg of MDMA hourly for a period of 4 hr on every fifth day from postnatal day 35-60. Acute effects of the MDMA treatment included hypothermia, serotonin syndrome behavior, and ejaculation. Body weight gain was attenuated by repeated drug administration. The animals completed anxiety and working memory tests beginning 4 days after the final MDMA dose. MDMA altered habituation to the open-field, increased locomotor activity in the elevated plus-maze, decreased attention in the novel object-recognition test, and reduced serotonin transporter binding in the neocortex. These results indicate that repeated exposure to a relatively moderate MDMA dose during adolescence produces later changes in behavior and neurochemistry. Copyright 2005 Wiley Periodicals, Inc

Reduction of the nocturnal rise in pineal melatonin levels in rats exposed to 60-Hz electric fields in utero and for 23 days after birth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reiter, R.J.; Anderson, L.E.; Buschbom, R.I.

Rats exposed to 60-Hz electric fields of either 10, 65, or 130 kV/m from conception to 23 days of age exhibited reduced peak nighttime pineal melatonin contents compared to unexposed controls. As a group, the exposed rats also exhibited a phase delay, estimated at approximately 1.4 hours, in the occurrence of the nocturnal melatonin peak. No clear dose-response relationship was noticed over the range of electric field strengths used as treatments in these experiments. These are the first studies concerned with the effects of electric field exposure on the pineal melatonin rhythm in immature rats and the findings are generallymore » consistent with those obtained using adult rats, where electric field exposure has been shown to abolish the nighttime rhythm in pineal melatonin concentrations. 15 refs., 1 fig., 1 tab.« less

Reduction of the nocturnal rise in pineal melatonin levels in rats exposed to 60-Hz electric fields in utero and for 23 days after birth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reiter, R.J.; Anderson, L.E.; Buschbom, R.L.

Rats exposed to 60-Hz electric fields of either 10, 65, or 130 kV/m from conception to 23 days of age exhibited reduced peak nighttime pineal melatonin contents compared to unexposed controls. As a group, the exposed rats also exhibited a phase delay, estimated at approximately 1.4 hours, in the occurrence of the nocturnal melatonin peak. No clear dose-response relationship was noticed over the range of electric field strengths used as treatments in these experiments. These are the first studies concerned with the effects of electric field exposure on the pineal melatonin rhythm in immature rats. The findings are generally consistentmore » with those obtained using adult rats, where electric field exposure has been shown to abolish the nighttime rhythm in pineal melatonin concentrations.« less

[A comparative study on behaviors of two depression models in rats induced by chronic forced swimming stress].

PubMed

Han, Ming-Fei; Gao, Dong; Sun, Xue-Li

2010-01-01

To compare the behaviors of rats with depressions induced by chronic forced swimming stress under two different conditions. Eighteen male rats were randomly divided into 3 groups, with 6 rats in each group. The rats in the control group (C group) were not forced into swimming, while the rats in the stress groups (S1 and S2) were forced to swim for 14 consecutive days. The rats in S1 group and S2 group swam for five minutes every morning, in water with (23 +/- 1) degree C, and (10 +/- 0.5) degree C in temperature, respectively. The weight gain, food intake, open-field test and saccharin solution test were observed on the seventh day and fourteenth day. On the seventh day following chronic swim stress, the rats in the S2 group had significant lower ratio in weight gain and food intake than the controls (P < 0.05). On the fourteenth day, the rats in the S2 group had significant lower ratio in weight gain (12.26 +/- 4.04)%, food intake (9.49 +/- 0.96)%, sucrose intake (28.63 +/- 3.51) g, and preference for saccharin solution (76.25 +/- 2.51)%, and less number of crossing (12.17 +/- 9.00) and times of rearing (3.17 +/- 3.60) than the controls (P < 0.05). The rats in the S1 group had significant lower ratio in weight gain and food intake than the controls on the seventh day following forced swimming. On the fourteenth day, the rats in the S1 group still had lower ratio in weight gain, but had higher ratio in food intake and preference for saccharin solution, and greater number of crossing than the controls. Chronic forced swimming at a lower temperature could induce depression better than at a higher temperature.

Behavioral and Neurochemical Effects of Alpha-Lipoic Acid in the Model of Parkinson's Disease Induced by Unilateral Stereotaxic Injection of 6-Ohda in Rat

PubMed Central

de Araújo, Dayane Pessoa; De Sousa, Caren Nádia Soares; Araújo, Paulo Victor Pontes; Menezes, Carlos Eduardo de Souza; Sousa Rodrigues, Francisca Taciana; Escudeiro, Sarah Souza; Lima, Nicole Brito Cortez; Patrocínio, Manoel Claúdio Azevedo; Aguiar, Lissiana Magna Vasconcelos; Viana, Glauce Socorro de Barros; Vasconcelos, Silvânia Maria Mendes

2013-01-01

This study aimed to investigate behavioral and neurochemical effects of α-lipoic acid (100 mg/kg or 200 mg/kg) alone or associated with L-DOPA using an animal model of Parkinson's disease induced by stereotaxic injection of 6-hydroxydopamine (6-OHDA) in rat striatum. Motor behavior was assessed by monitoring body rotations induced by apomorphine, open field test and cylinder test. Oxidative stress was accessed by determination of lipid peroxidation using the TBARS method, concentration of nitrite and evaluation of catalase activity. α-Lipoic acid decreased body rotations induced by apomorphine, as well as caused an improvement in motor performance by increasing locomotor activity in the open field test and use of contralateral paw (in the opposite side of the lesion produced by 6-OHDA) at cylinder test. α-lipoic acid showed antioxidant effects, decreasing lipid peroxidation and nitrite levels and interacting with antioxidant system by decreasing of endogenous catalase activity. Therefore, α-lipoic acid prevented the damage induced by 6-OHDA or by chronic use of L-DOPA in dopaminergic neurons, suggesting that α-lipoic could be a new therapeutic target for Parkinson's disease prevention and treatment. PMID:24023579

Behavioral consequences of exposure to a high fat diet during the post-weaning period in rats.

PubMed

Rabasa, Cristina; Winsa-Jörnulf, Julia; Vogel, Heike; Babaei, Carina S; Askevik, Kaisa; Dickson, Suzanne L

2016-09-01

We explored the impact of exposure to an obesogenic diet (High Fat-High Sucrose; HFS) during the post-weaning period on sweet preference and behaviors linked to reward and anxiety. All rats were fed chow. In addition a HFS-transient group had access to this diet for 10days from post-natal (PN) day 22 and a HFS-continuous group continued access until adult. Behavioral tests were conducted immediately after PN 32 (adolescence) or after PN 60 (adult) and included: the condition place preference (CPP) test for chocolate, sugar and saccharin preference (anhedonia), the elevated plus maze (anxiety-like behavior) and the locomotor response to quinpirole in the open field. Behavior was unaltered in adult rats in the HFS-transient group, suggesting that a short exposure to this obesogenic food does not induce long-term effects in food preferences, reward perception and value of palatable food, anxiety or locomotor activity. Nevertheless, rats that continued to have access to HFS ate less chocolate during CPP training and consumed less saccharin and sucrose when tested in adolescence, effects that were attenuated when these rats became adult. Moreover, behavioral effects linked to transient HFS exposure in adolescence were not sustained if the rats did not remain on that diet until adult. Collectively our data demonstrate that exposure to fat and sucrose in adolescence can induce immediate reward hypofunction after only 10days on the diet. Moreover, this effect is attenuated when the diet is extended until the adult period, and completely reversed when the HFS diet is removed. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Towards a better preclinical model of PTSD: characterizing animals with weak extinction, maladaptive stress responses and low plasma corticosterone.

PubMed

Reznikov, Roman; Diwan, Mustansir; Nobrega, José N; Hamani, Clement

2015-02-01

Most of the available preclinical models of PTSD have focused on isolated behavioural aspects and have not considered individual variations in response to stress. We employed behavioural criteria to identify and characterize a subpopulation of rats that present several features analogous to PTSD-like states after exposure to classical fear conditioning. Outbred Sprague-Dawley rats were segregated into weak- and strong-extinction groups on the basis of behavioural scores during extinction of conditioned fear responses. Animals were subsequently tested for anxiety-like behaviour in the open-field test (OFT), novelty suppressed feeding (NSF) and elevated plus maze (EPM). Baseline plasma corticosterone was measured prior to any behavioural manipulation. In a second experiment, rats underwent OFT, NSF and EPM prior to being subjected to fear conditioning to ascertain whether or not pre-stress levels of anxiety-like behaviours could predict extinction scores. We found that 25% of rats exhibit low extinction rates of conditioned fear, a feature that was associated with increased anxiety-like behaviour across multiple tests in comparison to rats showing strong extinction. In addition, weak-extinction animals showed low levels of corticosterone prior to fear conditioning, a variable that seemed to predict extinction recall scores. In a separate experiment, anxiety measures taken prior to fear conditioning were not predictive of a weak-extinction phenotype, suggesting that weak-extinction animals do not show detectable traits of anxiety in the absence of a stressful experience. These findings suggest that extinction impairment may be used to identify stress-vulnerable rats, thus providing a useful model for elucidating mechanisms and investigating potential treatments for PTSD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Agomelatine, venlafaxine, and running exercise effectively prevent anxiety- and depression-like behaviors and memory impairment in restraint stressed rats

PubMed Central

Lapmanee, Sarawut; Teerapornpuntakit, Jarinthorn; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2017-01-01

Several severe stressful situations, e.g., natural disaster, infectious disease out break, and mass casualty, are known to cause anxiety, depression and cognitive impairment, and preventive intervention for these stress complications is worth exploring. We have previously reported that the serotonin-norepinephrine-dopamine reuptake inhibitor, venlafaxine, as well as voluntary wheel running are effective in the treatment of anxiety- and depression-like behaviors in stressed rats. But whether they are able to prevent deleterious consequences of restraint stress in rats, such as anxiety/depression-like behaviors and memory impairment that occur afterward, was not known. Herein, male Wistar rats were pre-treated for 4 weeks with anti-anxiety/anti-depressive drugs, agomelatine and venlafaxine, or voluntary wheel running, followed by 4 weeks of restraint-induced stress. During the stress period, rats received neither drug nor exercise intervention. Our results showed that restraint stress induced mixed anxiety- and depression-like behaviors, and memory impairment as determined by elevated plus-maze, elevated T-maze, open field test (OFT), forced swimming test (FST), and Morris water maze (MWM). Both pharmacological pre-treatments and running successfully prevented the anxiety-like behavior, especially learned fear, in stressed rats. MWM test suggested that agomelatine, venlafaxine, and running could prevent stress-induced memory impairment, but only pharmacological treatments led to better novel object recognition behavior and positive outcome in FST. Moreover, western blot analysis demonstrated that venlafaxine and running exercise upregulated brain-derived neurotrophic factor (BDNF) expression in the hippocampus. In conclusion, agomelatine, venlafaxine as well as voluntary wheel running had beneficial effects, i.e., preventing the restraint stress-induced anxiety/depression-like behaviors and memory impairment. PMID:29099859

Agomelatine, venlafaxine, and running exercise effectively prevent anxiety- and depression-like behaviors and memory impairment in restraint stressed rats.

PubMed

Lapmanee, Sarawut; Charoenphandhu, Jantarima; Teerapornpuntakit, Jarinthorn; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2017-01-01

Several severe stressful situations, e.g., natural disaster, infectious disease out break, and mass casualty, are known to cause anxiety, depression and cognitive impairment, and preventive intervention for these stress complications is worth exploring. We have previously reported that the serotonin-norepinephrine-dopamine reuptake inhibitor, venlafaxine, as well as voluntary wheel running are effective in the treatment of anxiety- and depression-like behaviors in stressed rats. But whether they are able to prevent deleterious consequences of restraint stress in rats, such as anxiety/depression-like behaviors and memory impairment that occur afterward, was not known. Herein, male Wistar rats were pre-treated for 4 weeks with anti-anxiety/anti-depressive drugs, agomelatine and venlafaxine, or voluntary wheel running, followed by 4 weeks of restraint-induced stress. During the stress period, rats received neither drug nor exercise intervention. Our results showed that restraint stress induced mixed anxiety- and depression-like behaviors, and memory impairment as determined by elevated plus-maze, elevated T-maze, open field test (OFT), forced swimming test (FST), and Morris water maze (MWM). Both pharmacological pre-treatments and running successfully prevented the anxiety-like behavior, especially learned fear, in stressed rats. MWM test suggested that agomelatine, venlafaxine, and running could prevent stress-induced memory impairment, but only pharmacological treatments led to better novel object recognition behavior and positive outcome in FST. Moreover, western blot analysis demonstrated that venlafaxine and running exercise upregulated brain-derived neurotrophic factor (BDNF) expression in the hippocampus. In conclusion, agomelatine, venlafaxine as well as voluntary wheel running had beneficial effects, i.e., preventing the restraint stress-induced anxiety/depression-like behaviors and memory impairment.

Diphenyl diselenide diet intake improves spatial learning and memory deficits in hypothyroid female rats.

PubMed

Dias, Glaecir Roseni Mundstock; Vieira, Francielli Araújo; Dobrachinski, Fernando; Bridi, Jéssika Cristina; Balk, Rodrigo de Souza; Soares, Félix Antunes; Nogueira, Cristina Wayne; Barbosa, Nilda Berenice de Vargas

2012-04-01

Cognitive deficits have been observed in different animal models of adult-onset hypothyroidism. Thus, this study was delineated to evaluate whether diphenyl diselenide, an organoselenium compound with neuroprotective and antioxidant properties, could afford protection against the detrimental effects of hypothyroidism on behavioral parameters. Hypothyroidism condition was induced in female rats by continuous exposure to methimazole (MTZ) at 20 mg/100 ml in the drinking water, during 3 months. MTZ-induced hypothyroid rats were fed with either standard or a diet containing 5 ppm of diphenyl diselenide for 3 months. Behavioral assessments were performed monthly, in the following order: elevated plus maze, open field and Morris water maze. The levels of thyroid hormones in the animals exposed to MTZ were lower than control until the end of experimental period. The rats exposed to MTZ had a significant weight loss from the first month, which was not modified by diphenyl diselenide supplementation. In elevated plus maze test, MTZ exposure caused a reduction on the number of entries of animals in closed arms, which was avoided by diphenyl diselenide supplementation. In Morris water maze, the parameters latency to reach the platform and distance performed to find the escape platform in the test session were significantly greater in MTZ group when compared to control. These cognitive deficits observed in MTZ-induced hypothyroid rats were restored by dietary diphenyl diselenide. The group fed with diphenyl diselenide alone exhibited a better spatial learning and memory capability in some parameters of Morris water maze when compared to the control group. In summary, our data provide evidence of the effectiveness of dietary diphenyl diselenide in improving the performance of control and hypothyroid rats in the water maze test. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

Soluble Milk Protein Supplementation with Moderate Physical Activity Improves Locomotion Function in Aging Rats.

PubMed

Lafoux, Aude; Baudry, Charlotte; Bonhomme, Cécile; Le Ruyet, Pascale; Huchet, Corinne

2016-01-01

Aging is associated with a loss of muscle mass and functional capacity. Present study was designed to compare the impact of specific dairy proteins on muscular function with or without a low-intensity physical activity program on a treadmill in an aged rat model. We investigated the effects of nutritional supplementation, five days a week over a 2-month period with a slow digestible protein, casein or fast digestible proteins, whey or soluble milk protein, on strength and locomotor parameters in sedentary or active aged Wistar RjHan rats (17-19 months of age). An extensive gait analysis was performed before and after protein supplementation. After two months of protein administration and activity program, muscle force was evaluated using a grip test, spontaneous activity using an open-field and muscular mass by specific muscle sampling. When aged rats were supplemented with proteins without exercise, only minor effects of different diets on muscle mass and locomotion were observed: higher muscle mass in the casein group and improvement of stride frequencies with soluble milk protein. By contrast, supplementation with soluble milk protein just after physical activity was more effective at improving overall skeletal muscle function in old rats compared to casein. For active old rats supplemented with soluble milk protein, an increase in locomotor activity in the open field and an enhancement of static and dynamic gait parameters compared to active groups supplemented with casein or whey were observed without any differences in muscle mass and forelimb strength. These results suggest that consumption of soluble milk protein as a bolus immediately after a low intensity physical activity may be a suitable nutritional intervention to prevent decline in locomotion in aged rats and strengthen the interest to analyze the longitudinal aspect of locomotion in aged rodents.

Soluble Milk Protein Supplementation with Moderate Physical Activity Improves Locomotion Function in Aging Rats

PubMed Central

Lafoux, Aude; Baudry, Charlotte; Bonhomme, Cécile; Le Ruyet, Pascale; Huchet, Corinne

2016-01-01

Aging is associated with a loss of muscle mass and functional capacity. Present study was designed to compare the impact of specific dairy proteins on muscular function with or without a low-intensity physical activity program on a treadmill in an aged rat model. We investigated the effects of nutritional supplementation, five days a week over a 2-month period with a slow digestible protein, casein or fast digestible proteins, whey or soluble milk protein, on strength and locomotor parameters in sedentary or active aged Wistar RjHan rats (17–19 months of age). An extensive gait analysis was performed before and after protein supplementation. After two months of protein administration and activity program, muscle force was evaluated using a grip test, spontaneous activity using an open-field and muscular mass by specific muscle sampling. When aged rats were supplemented with proteins without exercise, only minor effects of different diets on muscle mass and locomotion were observed: higher muscle mass in the casein group and improvement of stride frequencies with soluble milk protein. By contrast, supplementation with soluble milk protein just after physical activity was more effective at improving overall skeletal muscle function in old rats compared to casein. For active old rats supplemented with soluble milk protein, an increase in locomotor activity in the open field and an enhancement of static and dynamic gait parameters compared to active groups supplemented with casein or whey were observed without any differences in muscle mass and forelimb strength. These results suggest that consumption of soluble milk protein as a bolus immediately after a low intensity physical activity may be a suitable nutritional intervention to prevent decline in locomotion in aged rats and strengthen the interest to analyze the longitudinal aspect of locomotion in aged rodents. PMID:27973615

Effects of intra-fourth ventricle injection of crocin on capsaicin-induced orofacial pain in rats.

PubMed

Tamaddonfard, Esmaeal; Tamaddonfard, Sina; Pourbaba, Salar

2015-01-01

Crocin, a constituent of saffron and yellow gardenia, possesses anti-nociceptive effects. In the present study, we investigated the effects of intra-fourth ventricle injection of crocin in a rat model of orofacial pain. The contribution of opioid system was assessed using intra-fourth ventricle injection of naloxone, an opioid receptor antagonist. A guide cannula was implanted into the fourth ventricle of brain in anesthetized rats. Orofacial pain was induced by subcutaneous (s.c.) injection of capsaicin (1.5 µg/20 µl) into the right vibrissa pad. The time spent face rubbing/grooming was recorded for a period of 20 min. Locomotor activity was measured using an open-field test. Intra-fourth ventricle injection of crocin (10 and 40 µg/rat) and morphine (10 and 40 µg/rat) and their co-administration (2.5 and 10 µg/rat of each) suppressed capsaicin-induced orofacial pain. The analgesic effect induced by 10 µg/rat of morphine, but not crocin (10 µg/rat), was prevented by 20 µg/rat of naloxone pretreatment. The above-mentioned chemical compounds did not affect locomotor activity. The results of this study showed that the injection of crocin into the cerebral fourth ventricle attenuates capsaicin-induced orofacial pain in rats. The anti-nociceptive effect of crocin was not attributed to the central opioid receptors.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Panek, R.L.; Dixon, W.R.; Rutledge, C.O.

The effect of dietary lipid treatment on sympathetic neuronal function was examined in isolated perfused tail arteries of adult rats. The hypothesis that dietary manipulations alter the lipid environment of receptor proteins which may result in the perturbation of specific membrane-associated processes that regulate peripheral adrenergic neurotransmission in the vasculature was the basis for this investigation. In the present study, rats were fed semisynthetic diets enriched in either 16% coconut oil (saturated fat) or 16% sunflower oil (unsaturated fat). The field stimulation-evoked release of endogenous norepinephrine and total /sup 3/H was decreased significantly in rats receiving the coconut oil dietmore » when compared to either sunflower oil- or standard lab chow-fed rats. Norepinephrine content in artery segments from coconut oil-treated rats was significantly higher compared to either sunflower oil- or standard lab chow-fed rats. Tail arteries from rats receiving the coconut oil diet displayed significantly lower perfusion pressure responses to nerve stimulation at all frequencies tested when compared to the sunflower oil- or standard lab chow-fed rats. Vasoconstrictor responses of perfused tail arteries exposed to exogenous norepinephrine resulted in an EC50 for norepinephrine that was not changed by the dietary treatment, but adult rats receiving the sunflower oil diet displayed a significantly greater maximum response to exogenous norepinephrine (10(-5) M) compared to arteries from either coconut oil- or standard lab chow-fed rats.« less

Oral 2-hydroxyoleic acid inhibits reflex hypersensitivity and open-field-induced anxiety after spared nerve injury.

PubMed

Avila-Martin, G; Galan-Arriero, I; Ferrer-Donato, A; Busquets, X; Gomez-Soriano, J; Escribá, P V; Taylor, J

2015-01-01

Recently, fatty acids have been shown to modulate sensory function in animal models of neuropathic pain. In this study, the antinociceptive effect of 2-hydroxyoleic acid (2-OHOA) was assessed following spared nerve injury (SNI) with reflex and cerebrally mediated behavioural responses. Initial antinociceptive behavioural screening of daily administration of 2-OHOA (400 mg/kg, p.o.) was assessed in Wistar rats by measuring hindlimb reflex hypersensitivity to von Frey and thermal plate stimulation up to 7 days after SNI, while its modulatory effect on lumbar spinal dorsal horn microglia reactivity was assessed with OX-42 immunohistochemistry. In vitro the effect of 2-OHOA (120 μM) on cyclooxygenase protein expression (COX-2/COX-1 ratio) in lipopolysaccharide-activated macrophage cells was tested with Western blot analysis. Finally, the effects of 2-OHOA treatment on the place escape aversion paradigm (PEAP) and the open-field-induced anxiety test were tested at 21 days following nerve injury compared with vehicle-treated sham and pregabalin-SNI (30 mg/kg, p.o.) control groups. Oral 2-OHOA significantly reduced ipsilateral mechanical and thermal hypersensitivity up to 7 days after SNI. Additionally 2-OHOA decreased the COX-2/COX-1 ratio in lipopolysaccharide-activated macrophage cells and OX-42 expression within the ipsilateral lumbar spinal dorsal horn 7 days after SNI. 2-OHOA significantly restored inner-zone exploration in the open-field test compared with the vehicle-treated sham group at 21 days after SNI. Oral administration of the modified omega 9 fatty acid, 2-OHOA, mediates antinociception and prevents open-field-induced anxiety in the SNI model in Wistar rats, which is mediated by an inhibition of spinal dorsal horn microglia activation. © 2014 European Pain Federation - EFIC®

Rats avoid high magnetic fields: dependence on an intact vestibular system

PubMed Central

Houpt, Thomas A.; Cassell, Jennifer A.; Riccardi, Christina; DenBleyker, Megan D.; Hood, Alison; Smith, James C.

2009-01-01

Summary HOUPT, T.A., J.A. CASSELL, C. RICCARDI, M.D. DENBLEYKER, A. HOOD, AND J.C. SMITH. Rats avoid high magnetic fields: dependence on an intact vestibular system. PHYSIOL BEHAV 00(0)000-000, 2006. High strength static magnetic fields are thought to be benign and largely undetectable by mammals. As magnetic resonance imaging (MRI) machines increase in strength, however, potential aversive effects may become clinically relevant. Here we report that rats find entry into a 14.1 T magnet aversive, and that they can detect and avoid entry into the magnet at a point where the magnetic field is 2 T or lower. Rats were trained to climb a ladder through the bore of a 14.1 T superconducting magnet. After their first climb into 14.1 T, most rats refused to re-enter the magnet or climb past the 2 T field line. This result was confirmed in a resistive magnet in which the magnetic field was varied from 1 to 14 T. Detection and avoidance required the vestibular apparatus of the inner ear, because labyrinthectomized rats readily traversed the magnet. The inner ear is a novel site for magnetic field transduction in mammals, but perturbation of the vestibular apparatus would be consistent with human reports of vertigo and nausea around high strength MRI machines. PMID:17585969

Potential behavioral and pro-oxidant effects of Petiveria alliacea L. extract in adult rats.

PubMed

de Andrade, Thaís Montenegro; de Melo, Ademar Soares; Dias, Rui Guilherme Cardoso; Varela, Everton Luís Pompeu; de Oliveira, Fábio Rodrigues; Vieira, José Luís Fernandes; de Andrade, Marcieni Ataíde; Baetas, Ana Cristina; Monteiro, Marta Chagas; Maia, Cristiane do Socorro Ferraz

2012-09-28

Petiveria alliacea (Phytolaccaceae) is a perennial shrub indigenous to the Amazon Rainforest and tropical areas of Central and South America, the Caribbean, and sub-Saharan Africa. In folk medicine, Petiveria alliacea has a broad range of therapeutic properties; however, it is also associated with toxic effects. The present study evaluated the putative effects of Petiveria alliacea on the central nervous system, including locomotor activity, anxiety, depression-like behavior, and memory, and oxidative stress. Two-month-old male and female Wistar rats (n=7-10 rats/group) were administered with 900 mg/kg of hydroalcoholic extracts of Petiveria alliacea L. The behavioral assays included open-field, forced swimming, and elevated T-maze tests. The oxidative stress levels were measured in rat blood samples after behavioral assays and methemoglobin levels were measured in vitro. Consistent with previous reports, Petiveria alliacea increased locomotor activity. It also exerted previously unreported anxiolytic and antidepressant effects in behavioral tests. In the oxidative stress assays, the Petiveria alliacea extract decreased Trolox equivalent antioxidant capacity levels and increased methemoglobin levels, which was related to the toxic effects. The Petiveria alliacea extract exerted motor stimulatory and anxiolytic effects in the OF test, antidepressant effects in the FS test, and elicited memory improvement in ETM. Furthermore, the Petiveria alliacea extract also exerted pro-oxidant effects in vitro and in vivo, inhibiting the antioxidant status and increasing MetHb levels in human plasma, respectively. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Antinociception induced by epidural motor cortex stimulation in naive conscious rats is mediated by the opioid system.

PubMed

Fonoff, Erich Talamoni; Dale, Camila Squarzoni; Pagano, Rosana Lima; Paccola, Carina Cicconi; Ballester, Gerson; Teixeira, Manoel Jacobsen; Giorgi, Renata

2009-01-03

Epidural motor cortex stimulation (MCS) has been used for treating patients with neuropathic pain resistant to other therapeutic approaches. Experimental evidence suggests that the motor cortex is also involved in the modulation of normal nociceptive response, but the underlying mechanisms of pain control have not been clarified yet. The aim of this study was to investigate the effects of epidural electrical MCS on the nociceptive threshold of naive rats. Electrodes were placed on epidural motor cortex, over the hind paw area, according to the functional mapping accomplished in this study. Nociceptive threshold and general activity were evaluated under 15-min electrical stimulating sessions. When rats were evaluated by the paw pressure test, MCS induced selective antinociception in the paw contralateral to the stimulated cortex, but no changes were noticed in the ipsilateral paw. When the nociceptive test was repeated 15 min after cessation of electrical stimulation, the nociceptive threshold returned to basal levels. On the other hand, no changes in the nociceptive threshold were observed in rats evaluated by the tail-flick test. Additionally, no behavioral or motor impairment were noticed in the course of stimulation session at the open-field test. Stimulation of posterior parietal or somatosensory cortices did not elicit any changes in the general activity or nociceptive response. Opioid receptors blockade by naloxone abolished the increase in nociceptive threshold induced by MCS. Data shown herein demonstrate that epidural electrical MCS elicits a substantial and selective antinociceptive effect, which is mediated by opioids.

Influence of Panax ginseng on the offspring of adult rats exposed to prenatal stress

PubMed Central

KIM, YOUNG OCK; LEE, HWA-YOUNG; WON, HANSOL; NAH, SEONG-SU; LEE, HWA-YOUNG; KIM, HYUNG-KI; KWON, JUN-TACK; KIM, HAK-JAE

2015-01-01

The exposure of pregnant females to stress during a critical period of fetal brain development is an environmental risk factor for the development of schizophrenia in adult offspring. Schizophrenia is a group of common mental disorders of unclear origin, affecting approximately 1% of the global population, showing a generally young age at onset. In the present study, a repeated variable stress paradigm was applied to pregnant rats during the final week of gestation. The effects of an extract of Panax ginseng C.A. Meyer (PG) on rats exposed to prenatal stress (PNS) were investigated in terms of behavioral activity and protein expression analyses. In the behavioral tests, grooming behavior in a social interaction test, line-crossing behavior in an open-field test and swimming activity in a forced-swim test were decreased in the rats exposed to PNS compared with the non-stressed offspring; the changes in behavioral activity were reversed upon oral treatment with PG (300 mg/kg). Subsequently, western blot analysis and immunohistochemical analyses of the prefrontal cortex and hippocampus revealed that the downregulation of several neurodevelopmental genes which occurred following exposure to PNS was reversed upon treatment with PG. The current findings demonstrate that the downregulation of several genes following exposure to PNS may affect subsequent behavioral changes, and that these phenomena are reversed following treatment with PG during pregnancy. Our results suggest that oral treatment with PG reduces the incidence of psychiatric disorders, such as schizophrenia. PMID:25394395

Age influences the effects of nicotine and monoamine oxidase inhibition on mood-related behaviors in rats.

PubMed

Villégier, Anne-Sophie; Gallager, Brittney; Heston, Jon; Belluzzi, James D; Leslie, Frances M

2010-03-01

Epidemiological studies have demonstrated a comorbidity of smoking with depression and anxiety, particularly during adolescence. However, few animal studies have considered possible synergistic interactions between nicotine and other tobacco smoke constituents, such as monoamine oxidase (MAO) inhibitors, in the regulation of mood. The aim of the study was to test the hypothesis that nicotine combined with the irreversible MAO inhibitor, tranylcypromine, will differentially affect depression- and anxiety-related behaviors in adolescent and adult rats. Nicotine (0, 0.05, 0.2 mg/kg, s.c.) and tranylcypromine (3 mg/kg, i.p.) were tested separately, or together, on male rats aged postnatal days 30 and 68, in three mood-related behavioral tests: forced swim test (FST), elevated plus maze (EPM), and open field. Nicotine (0.2 mg/kg) in adults significantly decreased floating time in the FST and increased time spent in the open arm of the EPM, with no change in locomotor activity. Tranylcypromine pretreatment combined with nicotine (0.2 mg/kg) significantly increased locomotor activity and time spent in the center of the open field. Whereas nicotine alone had no significant effect on adolescents, it significantly increased locomotor activity and decreased floating time in the FST when combined with tranylcypromine pretreatment. There is an age-dependent effect of nicotine, alone and in combination with MAO inhibition, on mood-related behaviors. Whereas nicotine alone induces mood improvement in adults, it has no effect on adolescents. Nicotine combined with tranylcypromine has unique, age-dependent effects. Thus, experimental studies of smoking should consider both age and other tobacco constituents, such as MAO inhibitors, as critical factors.

Effects of unpredictable chronic stress on behavior and brain-derived neurotrophic factor expression in CA3 subfield and dentate gyrus of the hippocampus in different aged rats.

PubMed

Li, Ying; Ji, Yong-juan; Jiang, Hong; Liu, De-xiang; Zhang, Qian; Fan, Shu-jian; Pan, Fang

2009-07-05

Brain-derived neurotrophic factor (BDNF) is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal (HPA) axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield (CA3) and dentate gyrus of hippocampus in different aged rats. Forty-eight Wistar rats of two different ages (2 months and 15 months) were randomly assigned to six groups: two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field (OF) test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry. Age and stress had different effects on the behavior of different aged animals (age: F = 6.173, P < 0.05, stress: F = 6.056, P < 0.05). Stress was the main factor affecting sucrose preference (F = 123.608, P < 0.05). Decreased sucrose preference and suppressed behavior emerged directly following stress, lasting to at least the eighth day after stress in young animals (P < 0.05). The older stress rats showed a lower sucrose preference than young stress rats (P < 0.05). Older control rats behaved differently from the younger control animals in the OF test, spending more time in the central square (P < 0.05), exhibiting fewer vertical movements (P < 0.05) and less grooming (P < 0.05). Following exposure to stress, older-aged rats showed no obvious changes in vertical movement and grooming. This indicates that aged rats were in an unexcited state before the stress period, and responded less to stressful stimuli than younger rats. There was significantly lower BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress in both age groups (P < 0.05), a reduction that was still present at the eighth day after stress (P < 0.05). Stress and age were the main factors affecting the expression of BDNF (F = 9.408, P < 0.05; F = 106.303, P < 0.05). The aged stress group showed lower BDNF expression compared to the young stressed group at every testing time point. Stress has age-dependent effects on behavioral responses and hippocampal BDNF expression in rats.

Response to novelty as a predictor of cocaine sensitization and conditioning in rats: a correlational analysis.

PubMed

Carey, Robert J; DePalma, Gail; Damianopoulos, Ernest

2003-07-01

An animal's response to novelty has been suggested to be a predictor of its response to drugs of abuse. The possible relationship between an individual's behavioral response to novelty and its subsequent behavioral response to cocaine has not been subjected to a detailed correlational analysis. To use a repeated cocaine treatment protocol to induce cocaine sensitization and conditioned cocaine locomotor stimulant effects and to assess the relationship of these effects to pre-cocaine locomotor behavior in a novel environment. In two separate experiments, rats were given a 20-min test in a novel open-field environment. Subsequently, the rats were given a series of additional tests in conjunction with either saline or cocaine (10 mg/kg) treatments to induce cocaine sensitization and conditioned effects. The repeated cocaine treatments induced cocaine behavioral sensitization and conditioned effects. Correlational analyses showed that the initial 20-min novel environment test proved to be a strong predictor of an animal's subsequent saline activity level but did not predict the rats' behavioral acute and sensitized response to cocaine. When change in activity was used as the dependent variable, initial activity level was reliably negatively correlated with activity changes on cocaine tests as well as cocaine conditioning tests. The negative correlation between initial activity in a novel environment and the change in activity induced by cocaine indicates that low responders to environmental novelty tend to have the strongest response to cocaine. These results appear consistent with the classic initial value and response rate dependent analyses of stimulant drug effects.

High sucrose consumption induces memory impairment in rats associated with electrophysiological modifications but not with metabolic changes in the hippocampus.

PubMed

Lemos, C; Rial, D; Gonçalves, F Q; Pires, J; Silva, H B; Matheus, F C; da Silva, A C; Marques, J M; Rodrigues, R J; Jarak, I; Prediger, R D; Reis, F; Carvalho, R A; Pereira, F C; Cunha, R A

2016-02-19

High sugar consumption is a risk factor for metabolic disturbances leading to memory impairment. Thus, rats subject to high sucrose intake (HSu) develop a metabolic syndrome and display memory deficits. We now investigated if these HSu-induced memory deficits were associated with metabolic and electrophysiological alterations in the hippocampus. Male Wistar rats were submitted for 9 weeks to a sucrose-rich diet (35% sucrose solution) and subsequently to a battery of behavioral tests; after sacrifice, their hippocampi were collected for ex vivo high-resolution magic angle spinning (HRMAS) metabolic characterization and electrophysiological extracellular recordings in slices. HSu rats displayed a decreased memory performance (object displacement and novel object recognition tasks) and helpless behavior (forced swimming test), without altered locomotion (open field). HRMAS analysis indicated a similar hippocampal metabolic profile of HSu and control rats. HSu rats also displayed no change of synaptic transmission and plasticity (long-term potentiation) in hippocampal Schaffer fibers-CA1 pyramid synapses, but had decreased amplitude of long-term depression in the temporoammonic (TA) pathway. Furthermore, HSu rats had an increased density of inhibitory adenosine A1 receptors (A1R), that translated into a greater potency of A1R in Schaffer fiber synapses, but not in the TA pathway, whereas the endogenous activation of A1R in HSu rats was preserved in the TA pathway but abolished in Schaffer fiber synapses. These results suggest that HSu triggers a hippocampal-dependent memory impairment that is not associated with altered hippocampal metabolism but is probably related to modified synaptic plasticity in hippocampal TA synapses. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Differential numbers of foci of lymphocytes within the brains of Lewis rats exposed to weak complex nocturnal magnetic fields during development of experimental allergic encephalomyelitis.

PubMed

Persinger, Michael A

2009-01-01

To discern if specific structures of the rat brain contained more foci of lymphocytes following induction of experimental allergic encephalomyelitis and exposures to weak, amplitude-modulated magnetic fields for 6 min once per hour during the scotophase, the residuals between the observed and predicted values for the numbers of foci for 320 structures were obtained. Compared to the brains of sham-field exposed rats, the brains of rats exposed to 7-Hz 50 nT (0.5 mG) amplitude-modulated fields showed more foci within hippocampal structures and the dorsal central grey of the midbrain while those exposed to 7-Hz 500 nT (5 mG) fields showed greater densities within the hypothalamus and optic chiasm. The brains of rats exposed to either the 50 nT or 500 nT amplitude-modulated 40-Hz fields displayed greater densities of foci within the midbrain structures related to rapid eye movement. Most of the enhancements of infiltrations within the magnetic field-exposed rats occurred in structures within periventricular or periaqueductal regions and were both frequency- and intensity-dependent. The specificity and complexity of the configurations of the residuals of the numbers of infiltrated foci following exposures to the different fields suggest that the brain itself may be a "sensory organ" for the detection of these stimuli.

Positively reinforcing effects of the neurokinin substance P in the basal forebrain: mediation by its C-terminal sequence.

PubMed

Hasenöhrl, R U; Gerhardt, P; Huston, J P

1992-02-01

The conditioned corral preference paradigm was used to assess reinforcing effects of substance P (SP) and its N- and C-terminal fragments injected unilaterally into the region of the nucleus basalis magnocellularis (NBM) in rats. Behavioral testing was carried out in a circular open field, consisting of 4 quadrants equally preferred by the animals prior to conditioning. A single conditioning trial was performed. Rats received one microinjection (0.5 microliter) of SP (0.74 pmol), of the N-terminal fragment SP (1-7) and the C-terminal fragment analog DiMe-C7 (each at doses of 0.074, 0.74, and 74 pmol), or vehicle (phosphate-buffered saline; PBS). After injection the rats were placed into the open field with the four quadrants being separated by Plexiglas barriers (closed corral). During the test for conditioned corral preference, when provided a choice between the four quadrants, only those rats injected with SP and the equimolar dose of DiMe-C7 (0.74 pmol) spent more time in the treatment corral, indicative of a positively reinforcing action. None of the other doses of DiMe-C7 and of SP(1-7) influenced the preference behavior. For rats injected with 0.74 pmol SP, SP (1-7), and DiMe-C7, a behavioral analysis was performed for the 15 min conditioning trial. SP and DiMe-C7 reduced rearing and grooming behavior, whereas DiMe-C7 and SP(1-7) increased locomotor activity. However, the acute behavioral effects of SP and its fragments were not correlated with the subsequent place preference behavior during the test trial. The results are discussed in the framework of a structure/activity relationship for the positively reinforcing properties of SP in the region of the NBM. Furthermore, neuropathological implications of the present data are considered, since the homologous nucleus basalis of Meynert in man is known to degenerate in Alzheimer's disease, which is characterized behaviorally by a progressive deterioration in associative functioning.

Effects of environmental enrichment on the activity of the amygdala in micrencephalic rats exposed to a novel open field.

PubMed

Matsuda, Wakoto; Ehara, Ayuka; Nakadate, Kazuhiko; Yoshimoto, Kanji; Ueda, Shuichi

2018-01-01

Environmental enrichment (EE) mediates recovery from sensory, motor, and cognitive deficits and emotional abnormalities. In the present study, we examined the effects of EE on locomotor activity and neuronal activity in the amygdala in control and methylazoxymethanol acetate (MAM)-induced micrencephalic rats after challenge in a novel open field. Control rats housed in EE (CR) showed reduced locomotor activity compared to rats housed in a conventional cage (CC), whereas hyperactivity was seen in MAM rats housed in a conventional cage (MC) and in MAM rats housed in EE (MR). Novel open field exposure in both CC and MC resulted in a marked increase in Fos expression in the anterior and posterior parts of the basolateral amygdaloid nucleus, basomedial nucleus, and medial nucleus, whereas these increases in expression were not observed in CR. The effect of EE on Fos expression in the amygdala was different in MR exposed to a novel open field compared to CR. Furthermore, we observed a quite different pattern of Fos expression in the central nucleus of the amygdala between control and MAM rats. The present results suggest that neuronal activity in the amygdala that responds to anxiety is altered in MAM rats, especially when the rats are reared in EE. These alterations may cause behavioral differences between control and MAM rats. © 2017 Japanese Teratology Society.

Analgesic effect of simultaneous exposure to infrared laser radiation and μT magnetic field in rats

NASA Astrophysics Data System (ADS)

Cieslar, Grzegorz; Mrowiec, Janina; Kasperczyk, Slawomir; Sieron-Stoltny, Karolina; Sieron, Aleksander

2008-03-01

The aim of the experiment was to estimate the effect of repeated simultaneous exposures to infrared laser radiation and μT variable magnetic field used in magnetostimulation on pain perception in rats, as well as the involvement of endogenous opioid system in the mechanism of this effect. In experimental group clean-shaven scull of male Wistar rats placed individually in a specially designed plastic chamber were simultaneously exposed to infrared laser radiation (wavelength - 855 nm, mean power - 4,1 mW, energy density - 30 J/cm2) and variable magnetic field of saw-like shape of impulse, at a frequency of basic impulse 180-195 Hz and mean induction value of 120 μT generated by magneto-laser applicator of device for magnetostimulation Viofor JPS (Med & Life, Poland) 12 minutes daily for 2 periods of 5 consecutive days, with 2 days-lasting break between them, while control animals were sham-exposed. The pain perception was determined by means of "hot plate" test on the basis of calculated analgesic index. As a result of repeated exposures a significant increase in analgesic index persisting also till 14 th day after the end of a cycle of exposures was observed. This analgesic effect was inhibited by prior i.p. injection of opioid antagonist - Naloxone.

T-2 mycotoxin treatment of newborn rat pups does not significantly affect nervous system functions in adulthood.

PubMed

Varró, Petra; Béldi, Melinda; Kovács, Melinda; Világi, Ildikó

2018-03-01

T-2 toxin is primarily produced by Fusarium sp. abundant under temperate climatic conditions. Its main harmful effect is the inhibition of protein synthesis. Causing oxidative stress, it also promotes lipid peroxidation and changes plasma membrane phospholipid composition; this may lead to nervous system alterations. The aim of the present study was to examine whether a single dose of T-2 toxin administered at newborn age has any long-lasting effects on nervous system functions. Rat pups were treated on the first postnatal day with a single intraperitoneal dose of T-2 toxin (0.2 mg/bwkg). Body weight of treated pups was lower during the second and third week of life, compared to littermates; later, weight gain was recovered. At young adulthood, behavior was tested in the open field, and no difference was observed between treated and control rats. Field potential recordings from somatosensory cortex and hippocampus slices did not reveal any significant difference in neuronal network functions. In case of neocortical field EPSP, the shape was slightly different in treated pups. Long-term synaptic plasticity was also comparable in both groups. Seizure susceptibility of the slices was not different, either. In conclusion, T-2 toxin did not significantly affect basic nervous system functions at this dose.

Determination of Leptospira borgpetersenii serovar Javanica and Leptospira interrogans serovar Bataviae as the persistent Leptospira serovars circulating in the urban rat populations in Peninsular Malaysia.

PubMed

Benacer, Douadi; Mohd Zain, Siti Nursheena; Sim, Shin Zhu; Mohd Khalid, Mohd Khairul Nizam; Galloway, Renee L; Souris, Marc; Thong, Kwai Lin

2016-03-01

Leptospirosis is an emerging infectious disease of global significance, and is endemic in tropical countries, including Malaysia. Over the last decade, a dramatic increase of human cases was reported; however, information on the primary vector, the rat, and the Leptospira serovars circulating among the rat population is limited. Therefore, the present study was undertaken to isolate Leptospira and characterise the serovars circulating in the urban rat populations from selected main cities in Peninsular Malaysia. Rat trappings were carried out between October 2011 to February 2014 in five urban cities which were chosen as study sites to represent different geographical locations in Peninsular Malaysia. Microscopic agglutination test (MAT) and PCR were carried out to identify the Leptospiral serogroup and determine the pathogenic status of the isolates, respectively while pulsed-field gel electrophoresis (PFGE) and random amplified polymorphic DNA (RAPD)-PCR were used to characterize the isolates. Three rat species were identified from the three hundred and fifty seven rats captured with Rattus rattus, being the dominant rat species (285, 80 %) followed by Rattus norgevicus (53, 15 %) and Rattus exulans (19, 5 %). Only 39 samples (11.0 %) were positive by culture and further confirmed as pathogenic Leptospira by PCR. Significant associations were shown between host infection with locality, season, host-age and species. Based on MAT, two serogroups were identified in the population namely; L. borgpetersenii serogroup Javanica (n = 16) and L. interrogans serogroup Bataviae (n = 23). Pulsed-field gel electrophoresis (PFGE) distinguished the two serovars in the urban rat populations: L. borgpetersenii serovar Javanica (41 %), and L. interrogans serovar Bataviae (59 %). RAPD-PCR yielded 14 distinct patterns and was found to be more discriminative than PFGE. This study confirms two Leptospira serovars circulating among the urban rats population in Peninsular Malaysia namely; L. borgpetersenii serovar Javanica and L. interrogans serovars Bataviae. Despite the low number of isolates obtained from the rat population, this study suggests that rodent control programs and disease surveillance may help to reduce the possible risk of disease transmission.

Extremely Low Frequency (ELF) Vertical Electric Field Exposure of Rats: Irradiation Facility

DTIC Science & Technology

1977-05-01

altered inside an animal cage even with wet or dry litter and full food and water containers. Rats weighing approximately 300 g in adjacent cages caused...with guard circuit Field inside empty cage Field inside complete cage ( litter (wet or dry) + food + water) Field variations caused by 300 g rat...blanket 250 Iron 60 Broiler 130 Hair dryer 40 Vaporizer 40 Refrigerator 60 Color TV 30 Stereo 90 Coffee pot 30 Vacuum cleaner 16 Clock radio

Modification of Anxious Behavior after Psychogenic Trauma and Treatment with Galanin Receptor Antagonist.

PubMed

Lyudyno, V I; Tsikunov, S G; Abdurasulova, I N; Kusov, A G; Klimenko, V M

2015-07-01

Effects of blockage of central galanin receptors on anxiety manifestations were studied in rats with psychogenic trauma. Psychogenic trauma was modeled by exposure of a group of rats to the situation when the partner was killed by a predator. Antagonist of galanin receptors was intranasally administered before stress exposure. Animal behavior was evaluated using the elevated-plus maze test, free exploratory paradigm, and open-field test. Psychogenic trauma was followed by an increase in anxiety level and appearance of agitated behavior. Blockage of galanin receptors aggravated behavioral impairment, which manifested in the pathological anxious reactions - manifestations of hypervigilance and hyperawareness. The results suggest that endogenous pool of galanin is involved into prevention of excessive CNS response to stressful stimuli typical of posttraumatic stress disorder.

Effects of physical exercise and social isolation on anxiety-related behaviors in two inbred rat strains.

PubMed

Mazur, F G; Oliveira, L F G; Cunha, M P; Rodrigues, A L S; Pértile, R A N; Vendruscolo, L F; Izídio, G S

2017-09-01

We investigated the effects of physical exercise (PE) on locomotor activity and anxiety-like behavior in Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) male rats. Rats received either four weeks of forced training, 5days/week, on a treadmill (experiment 1) or were given 21days of free access to running wheels (experiment 2). We also tested the effects of social isolation (SI) (seven days of isolation - experiment 3) on behavior. In experiment 1, 20% of LEW rats and 63% of SHR rats completed the training protocol. PE significantly increased central and peripheral locomotion in the open field (OF) and entries into the open arms in the elevated plus-maze (EPM) in both strains. In experiment 2, the distance traveled by SHR rats on running wheels was significantly higher compared with LEW rats. PE on running wheels also increased the time spent in the center of the OF in SHR rats only. In experiment 3, SI decreased central and peripheral locomotion in the OF in both strains. In summary, forced PE on a treadmill reduced anxiety-like behavior and increased locomotion in male rats of both strains, whereas voluntary PE on running wheels decreased anxiety-like behavior in SHR rats only. SI decreased locomotion in both strains in the OF. This study suggests that spontaneous activity levels are genotype-dependent and the effects of PE depend on the type of exercise performed. Copyright © 2017 Elsevier B.V. All rights reserved.

[Influence of environmental enrichment on parameters of behavior in open field test in the rats born from females with chronic alcoholization].

PubMed

Vakhnin, V A; Briukhin, G V

2014-04-01

The aim of this work was studying of morphology of a brain and the analysis of behavior at posterity of females of rats with a chronic alcoholic intoxication. As object of research were taken 60-day animals received from mothers with chronic alcoholic injury of hepatobiliary systems. During certain time (1.5 months) the part of animals grew in standard conditions, and another--in the "enriched" environment. The behavior analysis was spent in the open field test. Also was carried out research of a thickness of a cortex and a molecular layer of a forebrain. Work included three series of experiments. It is established, that the posterity of mothers with chronic injury of the hepatobiliary systems is characterized by the lowered motorial and research activity, increased by emotional reactivity that is accompanied by changes of structure of a cortex. The long finding of "alcoholic" animals in the "enriched" environment within 1.5 months promoted increasing of motorial and research activity, emotional reactance, change of structure of a cortex.

Voluntary exercise impact on cognitive impairments in sleep-deprived intact female rats.

PubMed

Rajizadeh, Mohammad Amin; Esmaeilpour, Khadijeh; Masoumi-Ardakani, Yaser; Bejeshk, Mohammad Abbas; Shabani, Mohammad; Nakhaee, Nouzar; Ranjbar, Mohammad Pour; Borzadaran, Fatemeh Mohtashami; Sheibani, Vahid

2018-05-01

Sleep loss is a common problem in modern societies affecting different aspects of individuals' lives. Many studies have reported that sleep deprivation (SD) leads to impairments in various types of learning and memory. Physical exercise has been suggested to attenuate the cognitive impairments induced by sleep deprivation in male rats. Our previous studies have shown that forced exercise by treadmill improved learning and memory impairments following SD. The aim of the current study was to investigate the effects of voluntary exercise by running wheel on cognitive, motor and anxiety-like behavior functions of female rats following 72 h SD. Intact female rats were used in the present study. The multiple platform method was applied for the induction of 72 h SD. The exercise protocol was 4 weeks of running wheel and the cognitive function was evaluated using Morris water maze (MWM), passive avoidance and novel object recognition tests. Open field test and measurement of plasma corticosterone level were performed for evaluation of anxiety-like behaviors. Motor balance evaluation was surveyed by rotarod test. In this study, remarkable learning and long-term memory impairments were observed in sleep deprived rats in comparison to the other groups. Running wheel exercise ameliorated the SD-induced learning and memory impairments. Voluntary and mandatory locomotion and balance situation were not statistically significant among the different groups. Our study confirmed the negative effects of SD on cognitive function and approved protective effects of voluntary exercise on these negative effects. Copyright © 2018 Elsevier Inc. All rights reserved.

Can safe and long-term exposure to extremely low frequency (50 Hz) magnetic fields affect apoptosis, reproduction, and oxidative stress?

PubMed

Akdag, Mehmet Zulkuf; Dasdag, Suleyman; Uzunlar, Ali Kemal; Ulukaya, Engin; Oral, Arzu Yilmaztepe; Çelik, Necla; Akşen, Feyzan

2013-12-01

To determine whether 50 Hz extremely low frequency-magnetic fields (ELF-MF) affects apoptotic processes, oxidative damage, and reproductive characteristics such as sperm count and morphology in rat testes. Thirty male Sprague-Dawley rats were used in the present study, which were divided into three groups (sham group, n = 10, and two experimental groups, n = 10 for each group). Rats in the experimental group were exposed to 100 and 500 μT ELF-MF (2 h/day, 7 days/week, for 10 months) corresponding to exposure levels that are considered safe for humans. The same experimental procedures were applied to the sham group, but the ELF generator was turned off. Tissues from the testes were immunohistochemically stained for active (cleaved) caspase-3 in order to measure the apoptotic index by a semi-quantitative scoring system. The levels of catalase (CAT), malondialdehyde (MDA), myeloperoxidase (MPO), total antioxidative capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) were also measured. Additionally, epididymal sperm count and sperm morphology was evaluated. There were no significant differences in the reproductive and oxidative stress parameters between the sham group and the exposed groups (p > 0.05). While no difference was observed between the final apoptosis score of the sham and the 100 μT ELF-MF group (p > 0.05), the final apoptosis score was higher in the 500 μT ELF-MF exposure group than in the sham group (p < 0.05). Long-term exposure to 100 μT and 500 μT ELF-MF did not affect oxidative or antioxidative processes, lipid peroxidation, or reproductive components such as sperm count and morphology in testes tissue of rats. However, long-term exposure to 500 μT ELF-MF did affect active-caspase-3 activity, which is a well-known apoptotic indicator.

Protective Effects of Tualang Honey against Oxidative Stress and Anxiety-Like Behaviour in Stressed Ovariectomized Rats

PubMed Central

Al-Rahbi, Badriya; Zakaria, Rahimah; Othman, Zahiruddin; Hassan, Asma'; Ahmad, Asma Hayati

2014-01-01

The present study aims to evaluate the antioxidant and anxiolytic-like effect of Tualang honey in stressed ovariectomized (OVX) rats. The animals were divided into; (i) nonstressed sham-operated control rats, (ii) sham-operated control rats exposed to stress, (iii) nonstressed OVX rats, (iv) OVX rats exposed to stress, (v) OVX rats exposed to stress and treated with 17 β-oestradiol (E2) (20 μg daily, sc), and (vi) OVX rats exposed to stress and treated with Tualang honey (0.2 g/kg body weight, orally). The open field test was used to evaluate the anxiety-like behaviour and ELISA kits were used to measure oxidant/antioxidant status of the brain homogenates. The result showed that anxiety-like behavior was significantly increased in stressed OVX compared to other groups, and administering either E2 or Tualang honey significantly decreased anxiety-like behaviour in stressed OVX rats. The levels of malondialdehyde (MDA) and protein carbonyl (PCO) were significantly decreased while the levels/activities of superoxide dismutase (SOD), glutathione S-transferases (GST), glutathione peroxidase (GPx), and glutathione reductase (GR) were significantly increased in the brain homogenates of treated stressed OVX groups compared to untreated stressed OVX. In conclusion, Tualang honey has protective effects against brain oxidative stress and may be useful alternative anxiolytic agent especially for postmenopausal women. PMID:27379299

Maternal mobile phone exposure alters intrinsic electrophysiological properties of CA1 pyramidal neurons in rat offspring.

PubMed

Razavinasab, Moazamehosadat; Moazzami, Kasra; Shabani, Mohammad

2016-06-01

Some studies have shown that exposure to electromagnetic field (EMF) may result in structural damage to neurons. In this study, we have elucidated the alteration in the hippocampal function of offspring Wistar rats (n = 8 rats in each group) that were chronically exposed to mobile phones during their gestational period by applying behavioral, histological, and electrophysiological tests. Rats in the EMF group were exposed to 900 MHz pulsed-EMF irradiation for 6 h/day. Whole cell recordings in hippocampal pyramidal cells in the mobile phone groups did show a decrease in neuronal excitability. Mobile phone exposure was mostly associated with a decrease in the number of action potentials fired in spontaneous activity and in response to current injection in both male and female groups. There was an increase in the amplitude of the afterhyperpolarization (AHP) in mobile phone rats compared with the control. The results of the passive avoidance and Morris water maze assessment of learning and memory performance showed that phone exposure significantly altered learning acquisition and memory retention in male and female rats compared with the control rats. Light microscopy study of brain sections of the control and mobile phone-exposed rats showed normal morphology.Our results suggest that exposure to mobile phones adversely affects the cognitive performance of both female and male offspring rats using behavioral and electrophysiological techniques. © The Author(s) 2014.

Ineffectiveness of saxagliptin as a neuroprotective drug in 6-OHDA-lesioned rats.

PubMed

Turnes, Joelle de Melo; Bassani, Taysa Bervian; Souza, Leonardo C; Vital, Maria A B F

2018-05-16

To determine whether the drug saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor which is utilized for the treatment of Diabetes Mellitus, has neuroprotective effects in the animal model of Parkinson's disease (PD) induced by 6-hydroxydopamine (6-OHDA) in rats. Male Wistar rats (weighing 280-300 g) received a bilateral infusion of 6-OHDA in the substantia nigra. Twenty-four hours later, they were treated with saxagliptin (1 mg/kg, p.o) once daily, for 21 days. The motor function was evaluated using the open field and rotarod (RT) tests. In addition, cognition was assessed with the novel object recognition test (ORT). After the evaluation of the behavioural tests, the animals were transcardially perfused to perform immunohistochemistry staining for tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNpc). Saxagliptin impaired the memory of animals in the sham group. Saxagliptin treatment did not exhibit neuroprotection and it did not improve the cognitive and motor deficits in the 6-OHDA model of PD. Interestingly, when saxagliptin was administered to the sham animals, a cognitive decline was observed. Therefore, this drug should be investigated as a possible treatment for PTSD. © 2018 Royal Pharmaceutical Society.

Root bark of Morus alba ameliorates the depressive-like behaviors in diabetic rats.

PubMed

Ye, Mei; Ke, Yuting; Liu, Bingyang; Yuan, Yanyan; Wang, Fuyan; Bu, Shizhong; Zhang, Yisheng

2017-01-10

Diabetes-induced depression is one of the severe chronic complications of diabetes mellitus. Up to now, there are only a few effective medicines to prevent or manage the co-morbidity of diabetes and depression. The present study was to investigate the effect of root bark of Morus alba (RBM) on depressive-like behaviors in the diabetic rats established by a high fat diet and a low dose of streptozotocin. Depressive-like behaviors were measured by the open field test, locomotor activity test and forced swimming test. Plasma glucose and lipid parameters were also measured. Expression of Brain-derived neurotrophic factor (BDNF) and phosphorylation of extracellular signal-regulated kinase (ERK) and Akt in the prefrontal cortex (PFC) were assessed. The results showed that a 4-week administration of RBM (10g/kg, ig) significantly reversed the depressive-like behaviors. BDNF expression and phosphorylation of ERK and Akt were increased in the PFC following RBM treatment in the diabetic rats. The data demonstrated that RBM could improve the depressive-like behaviors induced by diabetes, suggesting a therapeutic potential of RBM for the diabetes-associated depression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hormonal status and test condition, but not sexual experience, modulate partner preference in female rats.

PubMed

Clark, Ann S; Kelton, Megan C; Guarraci, Fay A; Clyons, Erika Q

2004-05-01

A series of experiments was conducted to determine the contributions of hormonal status, test condition, and sexual experience to the display of partner preference by female rats. Preference for a sexually active male rat over a sexually receptive female rat was assessed in independent groups of female rats tested in a condition limiting physical contact (No Contact) and a condition allowing for sexual interaction (Contact). Although hormonal status and test condition influenced the preference for a sexually active male, repeated testing and sexual experience had no effect. Experiment 1 demonstrated that independent of test condition, preference for the male is stronger in estrogen- and progesterone-primed rats than in rats receiving the vehicle. Moreover, independent of hormone condition, rats tested in the No Contact condition exhibit a stronger preference for the male than rats tested in the Contact condition, reflecting in part the active pacing of mating stimulation by sexually receptive rats tested in the Contact condition. Experiment 2 showed that the overall pattern of partner preference in proestrous and diestrous rats was similar to that observed in ovariectomized, estrogen- and progesterone-primed, and oil-treated rats, respectively. In Experiment 3, rats primed with estrogen alone did not exhibit a preference for the male even though fully receptive. Experiments 4 and 5 demonstrated that sexual experience does not affect the expression of preference for the male in estrogen- and progesterone-primed rats. The present findings demonstrate that the female rat's preference for the male is stable across repeated tests and is not affected by sexual experience. Our results also confirm that gonadal hormones influence the expression of a preference for a sexually active male versus a sexually receptive female and demonstrate that the magnitude of preference is modulated by test conditions.

Garcinia mangostana Linn displays antidepressant-like and pro-cognitive effects in a genetic animal model of depression: a bio-behavioral study in the Flinders Sensitive Line rat.

PubMed

Oberholzer, Inge; Möller, Marisa; Holland, Brendan; Dean, Olivia M; Berk, Michael; Harvey, Brian H

2018-04-01

There is abundant evidence for both disorganized redox balance and cognitive deficits in major depressive disorder (MDD). Garcinia mangostana Linn (GM) has anti-oxidant activity. We studied the antidepressant-like and pro-cognitive effects of raw GM rind in Flinders Sensitive Line (FSL) rats, a genetic model of depression, following acute and chronic treatment compared to a reference antidepressant, imipramine (IMI). The chemical composition of the GM extract was analysed for levels of α- and γ-mangostin. The acute dose-dependent effects of GM (50, 150 and 200 mg/kg po), IMI (20 mg/kg po) and vehicle were determined in the forced swim test (FST) in FSL rats, versus Flinders Resistant Line (FRL) control rats. Locomotor testing was conducted using the open field test (OFT). Using the most effective dose above coupled with behavioral testing in the FST and cognitive assessment in the novel object recognition test (nORT), a fixed dose 14-day treatment study of GM was performed and compared to IMI- (20 mg/kg/day) and vehicle-treated animals. Chronic treated animals were also assessed with respect to frontal cortex and hippocampal monoamine levels and accumulation of malondialdehyde. FSL rats showed significant cognitive deficits and depressive-like behavior, with disordered cortico-hippocampal 5-hydroxyindole acetic acid (5-HIAA) and noradrenaline (NA), as well as elevated hippocampal lipid peroxidation. Acute and chronic IMI treatment evoked pronounced antidepressant-like effects. Raw GM extract contained 117 mg/g and 11 mg/g α- and γ-mangostin, respectively, with acute GM demonstrating antidepressant-like effects at 50 mg/kg/day. Chronic GM (50 mg/kg/d) displayed significant antidepressant- and pro-cognitive effects, while demonstrating parity with IMI. Both behavioral and monoamine assessments suggest a more prominent serotonergic action for GM as opposed to a noradrenergic action for IMI, while both IMI and GM reversed hippocampal lipid peroxidation in FSL animals. Concluding, FSL rats present with cognitive deficits and depressive-like behaviors that are reversed by acute and chronic GM treatment, similar to that of IMI.

The effects of a time-based intervention on experienced middle-aged rats

PubMed Central

Peterson, Jennifer R.; Kirkpatrick, Kimberly

2016-01-01

Impulsive behavior is a common symptom in Attention Deficit Hyperactivity Disorder, schizophrenia, drug abuse, smoking, obesity and compulsive gambling. Stable levels of impulsive choice have been found in humans and rats and a recent study reported significant test-retest reliability of impulsive choice behavior after 1 and 5 months in rats. Time-based behavioral interventions have been successful in decreasing impulsive choices. These interventions led to improvements in the ability to time and respond more appropriately to adventitious choices. The current study examined the use of a time-based intervention in experienced, middle-aged rats. This intervention utilized a variable interval schedule previously found to be successful in improving timing and decreasing impulsive choice. This study found that the intervention led to a decrease in impulsive choices and there was a significant correlation between the improvement in self-control and post-intervention temporal precision in middle-aged rats. Although there were no overall group difference in bisection performance, individual differences were observed, suggesting an improvement in timing. This is an important contribution to the field because previous studies have utilized only young rats and because previous research indicates a decrease in general timing abilities with age. PMID:27826006

Applicability of a gene expression based prediction method to SD and Wistar rats: an example of CARCINOscreen®.

PubMed

Matsumoto, Hiroshi; Saito, Fumiyo; Takeyoshi, Masahiro

2015-12-01

Recently, the development of several gene expression-based prediction methods has been attempted in the fields of toxicology. CARCINOscreen® is a gene expression-based screening method to predict carcinogenicity of chemicals which target the liver with high accuracy. In this study, we investigated the applicability of the gene expression-based screening method to SD and Wistar rats by using CARCINOscreen®, originally developed with F344 rats, with two carcinogens, 2,4-diaminotoluen and thioacetamide, and two non-carcinogens, 2,6-diaminotoluen and sodium benzoate. After the 28-day repeated dose test was conducted with each chemical in SD and Wistar rats, microarray analysis was performed using total RNA extracted from each liver. Obtained gene expression data were applied to CARCINOscreen®. Predictive scores obtained by the CARCINOscreen® for known carcinogens were > 2 in all strains of rats, while non-carcinogens gave prediction scores below 0.5. These results suggested that the gene expression based screening method, CARCINOscreen®, can be applied to SD and Wistar rats, widely used strains in toxicological studies, by setting of an appropriate boundary line of prediction score to classify the chemicals into carcinogens and non-carcinogens.

Sensory transduction of weak electromagnetic fields: role of glutamate neurotransmission mediated by NMDA receptors.

PubMed

Frilot, C; Carrubba, S; Marino, A A

2014-01-31

Subliminal electromagnetic fields (EMFs) triggered nonlinear evoked potentials in awake but not anesthetized animals, and increased glucose metabolism in the hindbrain. Field detection occurred somewhere in the head and possibly was an unrecognized function of sensory neurons in facial skin, which synapse in the trigeminal nucleus and project to the thalamus via glutamate-dependent pathways. If so, anesthetic agents that antagonize glutamate neurotransmission would be expected to degrade EMF-evoked potentials (EEPs) to a greater extent than agents having different pharmacological effects. We tested the hypothesis using ketamine which blocks N-methyl-d-aspartate (NMDA) receptors (NMDARs), and xylazine which is an α₂-adrenoreceptor agonist. Electroencephalograms (EEGs) of rats were examined using recurrence analysis to observe EEPs in the presence and absence of ketamine and/or xylazine anesthesia. Auditory evoked potentials (AEPs) served as positive controls. The frequency of observation of evoked potentials in a given condition (wake or anesthesia) was compared with that due to chance using the Fisher's exact test. EEPs were observed in awake rats but not while they were under anesthesia produced using a cocktail of xylazine and ketamine. In another experiment each rat was measured while awake and while under anesthesia produced using either xylazine or ketamine. EEPs and AEPs were detected during wake and under xylazine (P<0.05 in each of the four measurements). In contrast, neither EEPs nor AEPs were observed when anesthesia was produced partly or wholly using ketamine. The duration and latency of the EEPs was unaltered by xylazine anesthesia. The afferent signal triggered by the transduction of weak EMFs was likely mediated by NMDAR-mediated glutamate neurotransmission. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of buspirone, diazepam, and zolpidem on open field behavior, and brain [3H]muscimol binding after buspirone pretreatment.

PubMed

Siemiatkowski, M; Sienkiewicz-Jarosz, H; Członkowska, A I; Bidziński, A; Płaźnik, A

2000-07-01

The effects of 5-HT(1A) receptor agonist buspirone, a nonselective (diazepam), and a selective (zolpidem) GABA(A) receptor agonist were compared in the open field test of neophobia. Unhabituated rats were pretreated with the drugs once, prior to a first exposure to the open field, and their behavior was recorded both during this test and during a second trial 24 h later. It has been hypothesized that the decrease in exploratory activity observed during the second test session may be considered an adaptive reaction to the first day aversive experience (neophobia). If so, a selective modulation of 5-HT and GABA systems activity during the test could bring about significant changes in animal behavior on the retest. Buspirone at the lowest dose of 0.3 mg/kg revealed anxiolytic-like properties on the first day, whereas the action of diazepam and zolpidem was modulated by the dose-related sedative effect. At the dose of 2.4 mg/kg buspirone elicited delayed in time anxiolytic-like action, i.e., produced the antithigmotactic effect during the retrial 24 h later. Diazepam and zolpidem failed to exhibit similar profile of action. Autoradiography of [3H]muscimol binding after pretreatment of rats with buspirone showed a significant increase in the selective radioligand binding within the frontal cortex and a similar, near-significant tendency in the dentate gyrus of the hippocampus. The behavioral data validate buspirone as important drug for the treatment of anxiety disorders, devoid of disruptive influence on motor and cognitive processes. The open field test, as modified by us, appeared sensitive in distinguishing the behavioral profiles of action of different anxiolytic compounds, including 5-HT(1A) receptor agonist. The present results support the assumption that reduced turnover of 5-HT due to stimulation of 5-HT(1A) autoreceptors, may bring about changes in GABA(A) receptor system activity, in some brain structures, leading to the anxiolytic effect.

Effects of hesperidin on formaldehyde-induced toxicity in pregnant rats

PubMed Central

Merzoug, Sameha; Toumi, Mohamed Lamine

2017-01-01

This experimental study aimed to investigate the protective effect of a bioflavonoid, hesperidin (HP), on formaldehyde (FA)-related pathophysiological and behavioral outcomes in pregnant rats and developmental aspects in their offspring. Female Wistar rats were subjected to perigestational exposure to FA (2 mg/kg/day per os) with a concomitant treatment with HP (50 mg/kg/day per os). Pregnant rats were weighed throughout gestation and tested in two behavioral paradigms (elevated plus-maze and open field) at gestational days (GD) 1, 10 and 19 to evaluate the anxiety-like behavior and locomotive alterations. Another subset of rats was decapitated at GD19 to determine the hematological profile along with cortisol, 17β-estradiol, and progesterone plasma levels. Reproductive and fetal measures and observations were also performed to check for developmental deformities. Significant body weight loss, hemato-immune decline, hormonal changes, anxiety and lethargy signs, locomotor disabilities, reproductive failure and fetal weight decrease were observed in FA-exposed rats. Treatment with HP alleviated the reproductive and fetal weight defects. Its behavioral benefits were only seen at GD1 and 10. This flavanone ameliorated some hematological parameters, decreased cortisol levels and increased 17β-estradiol rates. A potential preventive impact of HP was found against FA toxicity in pregnant rats. PMID:28507483

Regulation of the kynurenine metabolism pathway by Xiaoyao San and the underlying effect in the hippocampus of the depressed rat.

PubMed

Wang, Jiajia; Li, Xiaofang; He, Shugui; Hu, Lijun; Guo, Jiewen; Huang, Xiangning; Hu, Jinqing; Qi, Yaoqun; Chen, Bin; Shang, Dewei; Wen, Yuguan

2018-03-25

Xiaoyao San (XYS) is a classic Chinese herbal formula for treatment of depression. The present study aimed to investigate the antidepressant effects of XYS in a rat model of chronic unpredictable mild stress (CUMS) and the underlying mechanisms. A CUMS rat model of depression was established via 4 weeks of unpredictable stimulation. Then the rats were orally administered paroxetine and XYS for 2 weeks with continued stress. Behavioral assessments, including an open field test (OFT), sucrose preference test (SPT) and forced swim test (FST), were conducted to evaluate the antidepressant effects of XYS. The concentrations in rat plasma of tryptophan (Trp) and its metabolic products, including kynurenine (Kyn) and quinolinic acid (QUIN), were determined using high performance liquid chromatography tandem mass spectrometry with electrochemical detection (HPLC-MS/MS). The mRNA and protein levels in rat hippocampus of depression-related brain derived neurotrophic factor (BDNF), cyclic AMP response element binding protein (CREB) and nerve cell adhesion molecule (NCAM) were determined by real-time qPCR and Western blot, respectively. Enzyme Linked Immunosorbent Assay (ELISA) was used to detect the activities of indoleamine 2,3-dioxygenase (IDO) and kynurenine-3-monooxygenase (KMO) in rat plasma. The results showed that a successful CUMS rat model was established through 4 weeks of continuous unpredictable stimulation, as indicated by the significant decrease in locomotor activity and increase in immobility time in the OFT, reduction in body weight and food intake etc. Compared with the normal group, the concentrations of Kyn and QUIN had significantly (p < 0.05) decreased at day 28 in the control group, but then improved after drug treatment with paroxetine and XYS. There were no obvious changes in the activities of IDO and KMO. Compared with the normal group, the mRNA of NCAM, CREB and BDNF were significantly down-regulated (p < 0.001) in the control group, BDNF gene was up-regulated by paroxetine or XYS treatment, NCAM and CREB gene did not change in XYS group, protein expressions of BDNF and CREB were significantly increased, and NCAM was significantly reduced (p < 0.05). XYS reversed the abnormalities of the tryptophan-kynurenine metabolic pathways in depressed rats and achieved an excellent antidepressant effect. Its direct impact may be observed as changes in biological indicators in rat hippocampus tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

Depressive disorder and gastrointestinal dysfunction after myocardial infarct are associated with abnormal tryptophan-5-hydroxytryptamine metabolism in rats

PubMed Central

Liu, Chunyan; Wang, Yangang

2017-01-01

In this study, we investigated the relationship between tryptophan-5-hydroxytryptamine metabolism, depressive disorder, and gastrointestinal dysfunction in rats after myocardial infarction. Our goal was to elucidate the physiopathologic bases of somatic/psychiatric depression symptoms after myocardial infarction. A myocardial infarction model was established by permanent occlusion of the left anterior descending coronary artery. Depression-like behavior was evaluated using the sucrose preference test, open field test, and forced swim test. Gastric retention and intestinal transit were detected using the carbon powder labeling method. Immunohistochemical staining was used to detect indoleamine 2,3-dioxygenase expression in the hippocampus and ileum. High-performance liquid chromatography with fluorescence and ultraviolet detection determined the levels of 5-hydroxytryptamine, its precursor tryptophan, and its metabolite 5-hydroxyindoleacetic acid in the hippocampus, distal ileum, and peripheral blood. All data were analyzed using one-way analyses of variance. Three weeks after arterial occlusion, rats in the model group began to exhibit depression-like symptoms. For example, the rate of sucrose consumption was reduced, the total and central distance traveled in the open field test were reduced, and immobility time was increased, while swimming, struggling and latency to immobility were decreased in the forced swim test. Moreover, the gastric retention rate and gastrointestinal transit rate were increased in the model group. Expression of indoleamine 2,3-dioxygenase was increased in the hippocampus and ileum, whereas 5-hydroxytryptamine metabolism was decreased, resulting in lower 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels in the hippocampus and higher levels in the ileum. Depressive disorder and gastrointestinal dysfunction after myocardial infarction involve abnormal tryptophan-5-hydroxytryptamine metabolism, which may explain the somatic, cognitive, and psychiatric symptoms of depression commonly observed after myocardial infarction. Peripheral 5-hydroxytryptamine is an important substance in the gut-brain axis, and its abnormal metabolism is a critical finding after myocardial infarct. PMID:28212441

Depressive disorder and gastrointestinal dysfunction after myocardial infarct are associated with abnormal tryptophan-5-hydroxytryptamine metabolism in rats.

PubMed

Lu, Xiaofang; Wang, Yuefen; Liu, Chunyan; Wang, Yangang

2017-01-01

In this study, we investigated the relationship between tryptophan-5-hydroxytryptamine metabolism, depressive disorder, and gastrointestinal dysfunction in rats after myocardial infarction. Our goal was to elucidate the physiopathologic bases of somatic/psychiatric depression symptoms after myocardial infarction. A myocardial infarction model was established by permanent occlusion of the left anterior descending coronary artery. Depression-like behavior was evaluated using the sucrose preference test, open field test, and forced swim test. Gastric retention and intestinal transit were detected using the carbon powder labeling method. Immunohistochemical staining was used to detect indoleamine 2,3-dioxygenase expression in the hippocampus and ileum. High-performance liquid chromatography with fluorescence and ultraviolet detection determined the levels of 5-hydroxytryptamine, its precursor tryptophan, and its metabolite 5-hydroxyindoleacetic acid in the hippocampus, distal ileum, and peripheral blood. All data were analyzed using one-way analyses of variance. Three weeks after arterial occlusion, rats in the model group began to exhibit depression-like symptoms. For example, the rate of sucrose consumption was reduced, the total and central distance traveled in the open field test were reduced, and immobility time was increased, while swimming, struggling and latency to immobility were decreased in the forced swim test. Moreover, the gastric retention rate and gastrointestinal transit rate were increased in the model group. Expression of indoleamine 2,3-dioxygenase was increased in the hippocampus and ileum, whereas 5-hydroxytryptamine metabolism was decreased, resulting in lower 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels in the hippocampus and higher levels in the ileum. Depressive disorder and gastrointestinal dysfunction after myocardial infarction involve abnormal tryptophan-5-hydroxytryptamine metabolism, which may explain the somatic, cognitive, and psychiatric symptoms of depression commonly observed after myocardial infarction. Peripheral 5-hydroxytryptamine is an important substance in the gut-brain axis, and its abnormal metabolism is a critical finding after myocardial infarct.

Effect of food azo dye tartrazine on learning and memory functions in mice and rats, and the possible mechanisms involved.

PubMed

Gao, Yonglin; Li, Chunmei; Shen, Jingyu; Yin, Huaxian; An, Xiulin; Jin, Haizhu

2011-08-01

Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. The present study was conducted to evaluate the toxic effect of tartrazine on the learning and memory functions in mice and rats. Animals were administered different doses of tartrazine for a period of 30 d and were evaluated by open-field test, step-through test, and Morris water maze test, respectively. Furthermore, the biomarkers of the oxidative stress and pathohistology were also measured to explore the possible mechanisms involved. The results indicated that tartrazine extract significantly enhanced active behavioral response to the open field, increased the escape latency in Morris water maze test and decreased the retention latency in step-through tests. The decline in the activities of catalase, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) as well as a rise in the level of malonaldehyde (MDA) were observed in the brain of tartrazine-treated rats, and these changes were associated with the brain from oxidative damage. The dose levels of tartrazine in the present study produced a few adverse effects in learning and memory functions in animals. The mechanisms might be attributed to promoting lipid peroxidation products and reactive oxygen species, inhibiting endogenous antioxidant defense enzymes and the brain tissue damage. Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. Since the last assessment carried out by the Joint FAO/WHO Expert Committee on Food Additives in 1964, many new studies have been conducted. However, there is a little information about the effects on learning and memory performance. The present study was conducted to evaluate the toxic effect of tartrazine on the learning and memory functions in animals and its possible mechanism involved. Based on our results, we believe that more extensive assessment of food additives in current use is warranted. © 2011 Institute of Food Technologists®

Genotoxic Potential of 1.6 GHz Wireless Communication Signal: In vivo Two-Year Bioassay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vijayalaxmi, Vijay; Sasser, Lyle B.; Morris, J E.

Timed-pregnant Fischer 344 rats (from nineteenth day of gestation) and their nursing offspring (until weaning) were exposed to a far-field 1.6 GHz Iridium wireless communication signal for 2 h/day, 5 days/week. Far-field whole-body exposures were conducted with a field intensity of 0.43 mW/cm 2 and whole-body average specific absorption rate (SAR) of 0.036 to 0.077 W/kg (0.10 to 0.22 W/kg in the brain). This was followed by chronic, head-only exposures of male and female offspring to a near-field 1.6 GHz signal for 2 h/day, 5 days/week, over 2 years. Near-field exposures were conducted at an SAR of 0.16 or 1.6more » W/kg in the brain. Concurrent sham-exposed and cage control rats were also included in the study. At the end of 2 years, all rats were necropsied. Bone marrow smears were examined for the extent of genotoxicity, assessed from the presence of micronuclei in polychromatic erythrocytes. The results indicated that the incidence of micronuclei/ 2000 polychromatic erythrocytes were not significantly different between 1.6 GHz-exposed, sham-exposed and cage control rats. The group mean frequencies were 5.6 6 1.8 (130 rats exposed to 1.6 GHz at 0.16 W/kg SAR), 5.4 6 1.5 (135 rats exposed to 1.6 GHz at 1.6 W/kg SAR), 5.6 6 1.7 (119 sham-exposed rats), and 5.8 6 1.8 (100 cage control rats). In contrast, positive control rats treated with mitomycin C exhibited significantly elevated incidence of micronuclei/2000 polychromatic erythrocytes in bone marrow cells; the mean frequency was 38.2 6 7.0 (five rats). Thus there was no evidence for excess genotoxicity in rats that were chronically exposed to 1.6 GHz compared to sham-exposed and cage controls.« less

The antidepressant effect of an antiulcer pentadecapeptide BPC 157 in Porsolt's test and chronic unpredictable stress in rats. A comparison with antidepressants.

PubMed

Sikiric, P; Separovic, J; Buljat, G; Anic, T; Stancic-Rokotov, D; Mikus, D; Marovic, A; Prkacin, I; Duplancic, B; Zoricic, I; Aralica, G; Lovric-Bencic, M; Ziger, T; Perovic, D; Rotkvic, I; Mise, S; Hanzevacki, M; Hahn, V; Seiwerth, S; Turkovic, B; Grabarevic, Z; Petek, M; Rucman, R

2000-01-01

Various antidepressants have antiulcer activity. Likewise, the models currently used in ulcers and depression disorders research have a considerable degree of similarity. Therefore, the possibility that depression disorders could be effectively influenced by a primary antiulcer agent with a cyto/organoprotective activity, such as the novel stomach pentadecapeptide BPC 157, was investigated in two rat depression assays. First, a forced swimming test (a Porsolt's procedure) was used. As a more severe procedure, chronic unpredictable stress (after 5 d of unpredictable stress protocol, once daily drug application during stress procedure, open field-immobility test assessment at fourth or sixth day of medication) was used. In a forced swimming test, a reduction of the immobility time in BPC 157 (10 microg, 10 ng x kg(-1) i.p.) treated rats corresponds to the activity of the 15 mg or 40 mg (i.p.) of conventional antidepressants, imipramine or nialamide, respectively, given according to the original Porsolt's protocol. In chronic unpredictable stress procedure, particular aggravation of experimental conditions markedly affected the conventional antidepressant activity, whereas BPC 157 effectiveness was continuously present. The effect of daily imipramine (30 mg) medication could be seen only after a more prolonged period, but not after a shorter period (i.e., 4-d protocol). In these conditions, no delay in the effectiveness was noted in BPC 157 medication and a reduction of the immobility of chronically stressed rats was noted after both 4 and 6 d of BPC 157 (10 microg, 10 ng) medication.

Adolescent environmental enrichment prevents behavioral and physiological sequelae of adolescent chronic stress in female (but not male) rats.

PubMed

Smith, Brittany L; Morano, Rachel L; Ulrich-Lai, Yvonne M; Myers, Brent; Solomon, Matia B; Herman, James P

2017-11-22

The late adolescent period is characterized by marked neurodevelopmental and endocrine fluctuations in the transition to early adulthood. Adolescents are highly responsive to the external environment, which enhances their ability to adapt and recover from challenges when given nurturing influences, but also makes them vulnerable to aberrant development when exposed to prolonged adverse situations. Female rats are particularly sensitive to the effects of chronic stress in adolescence, which manifests as passive coping strategies and blunted hypothalamo-pituitary adrenocortical (HPA) stress responses in adulthood. We sought to intervene by exposing adolescent rats to environmental enrichment (EE) immediately prior to and during chronic stress, hypothesizing that EE would minimize or prevent the long-term effects of stress that emerge in adult females. To test this, we exposed male and female rats to EE on postnatal days (PND) 33-60 and implemented chronic variable stress (CVS) on PND 40-60. CVS consisted of twice-daily unpredictable stressors. Experimental groups included: CVS/unenriched, unstressed/EE, CVS/EE and unstressed/unenriched (n = 10 of each sex/group). In adulthood, we measured behavior in the open field test and forced swim test (FST) and collected blood samples following the FST. We found that environmental enrichment given during the adolescent period prevented the chronic stress-induced transition to passive coping in the FST and reversed decreases in peak adrenocortical responsiveness observed in adult females. Adolescent enrichment had little to no effect on males or unstressed females tested in adulthood, indicating that beneficial effects are specific to females that were exposed to chronic stress.

Effects of mobile phone radiation (900 MHz radiofrequency) on structure and functions of rat brain.

PubMed

Saikhedkar, Nidhi; Bhatnagar, Maheep; Jain, Ayushi; Sukhwal, Pooja; Sharma, Chhavi; Jaiswal, Neha

2014-12-01

The goals of this study were: (1) to obtain basic information about the effects of long-term use of mobile phones on cytological makeup of the hippocampus in rat brains (2) to evaluate the effects on antioxidant status, and (3) to evaluate the effects on cognitive behavior particularly on learning and memory. Rats (age 30 days, 120 ± 5 g) were exposed to 900 MHz radio waves by means of a mobile hand set for 4 hours per day for 15 days. Effects on anxiety, spatial learning, and memory were studied using the open field test, the elevated plus maze, the Morris water maze (MWM), and the classic maze test. Effects on brain antioxidant status were also studied. Cresyl violet staining was done to assess the neuronal damage. A significant change in behavior, i.e., more anxiety and poor learning was shown by test animals as compared to controls and sham group. A significant change in the level of antioxidant enzymes and non-enzymatic antioxidants, and an increase in lipid peroxidation were observed in the test rats. Histological examination showed neurodegenerative cells in hippocampal sub regions and the cerebral cortex. Thus our findings indicate extensive neurodegeneration on exposure to radio waves. Increased production of reactive oxygen species due to exhaustion of enzymatic and non-enzymatic antioxidants and increased lipid peroxidation indicate extensive neurodegeneration in selective areas of CA1, CA3, DG, and the cerebral cortex. This extensive neuronal damage results in alterations in behavior related to memory and learning.

Gut vagal afferents differentially modulate innate anxiety and learned fear.

PubMed

Klarer, Melanie; Arnold, Myrtha; Günther, Lydia; Winter, Christine; Langhans, Wolfgang; Meyer, Urs

2014-05-21

Vagal afferents are an important neuronal component of the gut-brain axis allowing bottom-up information flow from the viscera to the CNS. In addition to its role in ingestive behavior, vagal afferent signaling has been implicated modulating mood and affect, including distinct forms of anxiety and fear. Here, we used a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method existing to date, to study the consequences of complete disconnection of abdominal vagal afferents on innate anxiety, conditioned fear, and neurochemical parameters in the limbic system. We found that compared with Sham controls, SDA rats consistently displayed reduced innate anxiety-like behavior in three procedures commonly used in preclinical rodent models of anxiety, namely the elevated plus maze test, open field test, and food neophobia test. On the other hand, SDA rats exhibited increased expression of auditory-cued fear conditioning, which specifically emerged as attenuated extinction of conditioned fear during the tone re-exposure test. The behavioral manifestations in SDA rats were associated with region-dependent changes in noradrenaline and GABA levels in key areas of the limbic system, but not with functional alterations in the hypothalamus-pituitary-adrenal grand stress. Our study demonstrates that innate anxiety and learned fear are both subjected to visceral modulation through abdominal vagal afferents, possibly via changing limbic neurotransmitter systems. These data add further weight to theories emphasizing an important role of afferent visceral signals in the regulation of emotional behavior. Copyright © 2014 the authors 0270-6474/14/347067-10$15.00/0.

Microglia depletion in early life programs persistent changes in social, mood-related, and locomotor behavior in male and female rats.

PubMed

Nelson, Lars H; Lenz, Kathryn M

2017-01-01

Microglia, the innate immune cells of the central nervous system, regulate brain development by promoting cell genesis, pruning synapses, and removing dying, newly-born or progenitor cells. However, the role of microglia in the early life programming of behavior under normal conditions is not well characterized. We used central infusion of liposomal clodronate to selectively deplete microglia from the neonatal rat brain and subsequently assessed the impact of microglial depletion on programming of juvenile and adult motivated behaviors. Liposomal clodronate treatment on postnatal days one and four led to greater than 70% loss of forebrain microglia by postnatal day 6 that lasted for approximately ten days. Neonatal microglia depletion led to reduced juvenile and adult anxiety behavior on the elevated plus maze and open field test, and increased locomotor activity. On a test of juvenile social play, microglial depletion led to decreased chase behaviors relative to control animals. There was no change in active social behavior in adults on a reciprocal social interaction test, but there was decreased passive interaction time and an increased number of social avoidance behaviors in clodronate treated rats relative to controls. There was an overall decrease in behavioral despair on the forced swim test in adult rats treated neonatally with clodronate. Females, but not males, treated neonatally with clodronate showed a blunted corticosterone response after acute stress in adulthood. These results show that microglia are important for the early life programming of juvenile and adult motivated behavior. Copyright © 2016 Elsevier B.V. All rights reserved.

Perinatal asphyxia in the guinea pig leads to morphologic but not neurologic, cognitive, or behavioral changes.

PubMed

Hoeger, Harald; Bubna-Littitz, Herrmann; Engelmann, Mario; Schwerdtner, Ingrid; Schmid, Diethard; Lahoda, Robert; Seidl, Rainer; Lubec, Gert; Lubec, Barbara

2003-07-01

In a recent publication, we described neurodegeneration along with neurotransmitter deficits and impaired differentiation in the guinea pig 3 months following severe perinatal asphyxia (PA). We were therefore interested in the clinical features in terms of neurology, cognitive functions, and behavior. We tested the long-term effects of PA in an animal model, which in the rat are well documented and resemble the clinical situation. Examinations consisted of an observational battery for motor and reflex functions and the acoustic startle response setting. We tested cognitive functions in the multiple T-maze and evaluated behavior using the elevated plus maze and open field studies. No neurologic deficits were observed in the observational battery, including the acoustic startle response. Cognitive functions of memory and learning were not impaired in the multiple T-maze. In the open field and in the elevated plus maze, the system to test anxiety-related behavior, guinea pigs performed well. Our findings of patent neurology, cognitive functions, and behavior do not reflect the prominent morphologic findings of neurodegeneration. This is in agreement with corresponding studies on PA in the rat at the identical time point. We learned from this study that both test systems, although representing the standard in neuroscience, are either not sensitive enough or central nervous system lesions are clinically fully compensated.

Neurotoxic effect of linamarin in rats associated with cassava (Manihot esculenta Crantz) consumption.

PubMed

Rivadeneyra-Domínguez, Eduardo; Vázquez-Luna, Alma; Rodríguez-Landa, Juan Francisco; Díaz-Sobac, Rafael

2013-09-01

Cassava (Manihot esculenta Crantz) is a plant widely used for food consumption in different processed products in rural areas of Africa, Asia, and Latin America. Cassava is a good source of carbohydrates and micronutrients. However, if it is not adequately processed or the consumer has nutritional deficiencies, then its cyanogenic glycoside (i.e., linamarin and lotaustralin) content makes it potentially neurotoxic. In the present study, the neurotoxic effects of different concentrations of linamarin (0.075, 0.15, 0.22, and 0.30 mg/kg) contained in cassava juice were evaluated in the open field and swim tests to identify locomotor alterations in adult male Wistar rats. The linamarin concentration in cassava juice was determined by high-performance liquid chromatography, and the juice was administered intraesophageally for 28 days. The results suggested that the consumption of linamarin in cassava juice increased the number of crossings and rearings in the open field test and caused behavioral deficiency, reflected by lateral swimming, in the swim test on days 21 and 28 of treatment. These alterations are possibly related to neuronal damage caused by linamarin in cassava juice in structures of the central nervous system involved in motor processing. Copyright © 2013 Elsevier Ltd. All rights reserved.

Central nervous system activity of the proanthocyanidin-rich fraction obtained from Croton celtidifolius in rats.

PubMed

Moreira, Eduardo L G; Rial, Daniel; Duarte, Filipe S; de Carvalho, Cristiane Ribeiro; Horst, Heros; Pizzolatti, Moacir G; Prediger, Rui D S; Ribeiro-do-Valle, Rosa Maria

2010-08-01

The aim of the present study was to evaluate the possible neurobehavioural effects in rats of the proanthocyanidin-rich fraction (PRF) isolated from the bark of Croton celtidifolius (Euphorbiaceae). Adult Wistar rats were treated with the PRF (0.3-30 mg/kg) and evaluated in different behavioural paradigms classically used for the screening of drugs with psychoactive effects. Acute intraperitoneal (i.p.) administration of PRF decreased spontaneous locomotor activity (open field arena and activity cage), enhanced the duration of ethyl ether-induced hypnosis, increased the latency to the first convulsion induced by pentylenetetrazole (60 mg/kg, i.p.) and attenuated apomorphine-induced (0.5 mg/kg, i.p.) stereotyped behaviour. In lower doses, PRF (0.3 or 3 mg/kg, i.p.) increased the frequency of open arm entries in the elevated plus-maze test. The present findings suggest that the systemic administration of PRF induces a wide spectrum of behavioural alterations in rats, consistent with the putative existence of hypnosedative, anticonvulsant and anxiolytic compounds.

Ketogenic diet does not impair spatial ability controlled by the hippocampus in male rats.

PubMed

Fukushima, Atsushi; Ogura, Yuji; Furuta, Miyako; Kakehashi, Chiaki; Funabashi, Toshiya; Akema, Tatsuo

2015-10-05

A ketogenic diet was recently shown to reduce glutamate accumulation in synaptic vesicles, decreasing glutamate transmission. We questioned whether a ketogenic diet affects hippocampal function, as glutamate transmission is critically involved in visuospatial ability. In the present study, male Wistar rats were maintained on a ketogenic diet containing 10% protein and 90% fat with complements for 3 weeks to change their energy expenditure from glucose-dependent to fat-dependent. Control rats were fed a diet containing 10% protein, 10% fat, and 80% carbohydrates. The fat-dependent energy expenditure induced by the ketogenic diet led to decreased body weight and increased blood ketone production, though the rats in the two groups consumed the same number of calories. The ketogenic diet did not alter food preferences for the control or high-fat diet containing 10% protein, 45% fat, and 45% carbohydrates. Anxiety in the open field was not altered by ingestion the ketogenic diet. However, rats fed the ketogenic diet performed better in the Y-maze test than rats fed the control diet. No difference was observed between the two groups in the Morris water maze test. Finally, Western blot revealed that the hippocampal expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor subunit 1 (GluR1) was significantly increased in mice fed a ketogenic diet. These results suggest that hippocampal function is not impaired by a ketogenic diet and we speculate that the fat-dependent energy expenditure does not impair visuospatial ability. Copyright © 2015 Elsevier B.V. All rights reserved.

Experimental gastritis leads to anxiety- and depression-like behaviors in female but not male rats

PubMed Central

2013-01-01

Human and animals studies support the idea that there is a gender-related co-morbidity of pain-related and inflammatory gastrointestinal (GI) diseases with psychological disorders. This co-morbidity is the evidence for the existence of GI-brain axis which consists of immune (cytokines), neural (vagus nerve) and neuroendocrine (HPA axis) pathways. Psychological stress causes disturbances in GI physiology, such as altered GI barrier function, changes in motility and secretion, development of visceral hypersensitivity, and dysfunction of inflammatory responses. Whether GI inflammation would exert impact on psychological behavior is not well established. We examined the effect of experimental gastritis on anxiety- and depression-like behaviors in male and female Sprague–Dawley rats, and evaluated potential mechanisms of action. Gastritis was induced by adding 0.1% (w/v) iodoacetamide (IAA) to the sterile drinking water for 7 days. Sucrose preference test assessed the depression-like behavior, open field test and elevated plus maze evaluated the anxiety-like behavior. IAA treatment induced gastric inflammation in rats of either gender. No behavioral abnormality or dysfunction of GI-brain axis was observed in male rats with IAA-induced gastritis. Anxiety- and depression-like behaviors were apparent and the HPA axis was hyperactive in female rats with IAA-induced gastritis. Our results show that gastric inflammation leads to anxiety- and depression-like behaviors in female but not male rats via the neuroendocrine (HPA axis) pathway, suggesting that the GI inflammation can impair normal brain function and induce changes in psychological behavior in a gender-related manner through the GI-to-brain signaling. PMID:24345032

Chronic neonatal N-methyl-D-aspartate receptor blockade induces learning deficits and transient hypoactivity in young rats.

PubMed

Latysheva, Nadejda V; Rayevsky, Kirill S

2003-08-01

A blockade of N-methyl-D-aspartate (NMDA)-type of glutamate receptor in rodents is believed to provide a pharmacological model of schizophrenia-related psychosis. Since neurodevelopmental abnormality, at least partly, could contribute to the pathogenesis of schizophrenia, the aim of this study was to recapitulate cognitive impairments accompanying this disorder in rats by a chronic neonatal treatment with a noncompetitive NMDA antagonist MK-801. Rat pups were treated with a low dose of MK-801 (0.05 mg/kg s.c.) chronically from early postnatal period (PD 7-49) known to be critical for glutamatergic system maturation. Locomotor activity in the "open-field" test, anxiety level in the elevated plus-maze test, and learning capacity in food rewarded spatial task were examined in young animals. Chronic MK-801 treatment produced a decrease of spontaneous motor and exploratory activity in 16- to 28-day-old rats. At the same time, a hyperlocomotion in response to acute administration of MK-801 was observed as well. Spatial learning of MK-801-treated rats was found to be negatively affected. Treated rats were able to respond to stress stimuli in the adequate manner but their anxiety level was found to be lower than in controls. Behavioral disturbances appeared to be temporary, and no such abnormalities could be detected at the age of 16 weeks. Thus, even mild chronic neonatal blockade of NMDA receptors may lead to a specific pattern of cognitive abnormalities presumably resulting from impairments of sensory information processing at the cortical-basal ganglia level.

Enhanced susceptibility to periodontitis in an animal model of depression: reversed by chronic treatment with the anti-depressant tianeptine.

PubMed

Breivik, Torbjørn; Gundersen, Yngvar; Myhrer, Trond; Fonnum, Frode; Osmundsen, Harald; Murison, Robert; Gjermo, Per; von Hörsten, Stephan; Opstad, Per Kristian

2006-07-01

To test the hypothesis that the olfactory bulbectomy model of depression in rats could influence susceptibility to ligature-induced periodontitis, and that chronic treatment with the anti-depressant drug tianeptine could attenuate this effect. Tianeptine was given twice daily (10 mg/kg, i.p.) during the entire experiment, starting 29 days before induction of olfactory bulbectomy and periodontitis. Olfactory bulbectomized (OB) rats and sham-operated rats were given saline in a similar manner. Periodontal disease was assessed when the ligatures had been in place for 21 days. Two hours before decapitation, rats were injected with lipopolysaccharide (LPS;100 microg/kg, i.p.) to induce a robust immune and stress response. Compared with sham-operated controls, OB rats developed significantly more periodontal bone loss, exhibited characteristic behavioural responses in a novel open field test, and showed a decreased expression of glucocorticoid receptors (GRs) in the hippocampus. LPS provoked a significantly larger increase in circulating levels of the stress hormone corticosterone and the cytokine transformation growth factor (TGF)-1beta but smaller tumour necrosis factor (TNF)-alpha levels. Tianeptine treatment of OB rats significantly inhibited peridodontal bone loss, normalized behavioural responses, enhanced TGF-1beta levels, and abolished TNF-alpha decrease, but did not attenuate the increased corticosterone response and the decreased hippocampal GR expression. These experimental results are consistent with an emerging literature showing that life stress, anxiety, depression, pathological grief, and poor coping behaviour may dysregulate regulatory mechanisms within the brain involved in immune regulation, and thereby alter immune responses and influence the susceptibility/resistance to inflammatory disorders.

Effect of diabetes and elevated glucose on nitric oxide-mediated neurotransmission in rat anococcygeus muscle.

PubMed Central

Way, K. J.; Reid, J. J.

1995-01-01

1. Nitric oxide (NO)-mediated neurotransmission is impaired in anococcygeus muscle from 8-week streptozotocin-induced diabetic rats. This study investigated the effects of insulin treatment, and the duration of diabetes on this impairment. In addition, the effect of in vitro exposure to elevated glucose has been investigated on NO-mediated relaxations, in muscles from untreated rats. 2. Relaxant responses to field stimulation (0.5-5 Hz, 10s train), sodium nitroprusside (SNP; 5 and 10 nM) and NO (1 and 3 microM) were significantly impaired in anococcygeus muscles from 8-week diabetic rats, compared to responses from control rats. Insulin treatment (5 u Lente day-1, s.c.) of diabetic rats prevented the development of this impairment. 3. Consistent with findings in 8-week diabetic rats, relaxation induced by field stimulation, SNP and NO were attenuated in tissues from 2-week and 4-week diabetic rats compared to corresponding control responses, whereas relaxations to papaverine (3 and 10 microM) were not reduced. In contrast, diabetes of 3-days duration did not affect relaxations to field stimulation, SNP or NO. 4. Incubation of anococcygeus muscles from untreated rats in medium containing elevated glucose (44.1 mM) for 6 h, significantly impaired relaxations to field stimulation compared to responses obtained after normal glucose (11.1 mM) incubation. Relaxations to SNP and to NO were not affected by 6 h exposure to elevated glucose. Similarly, incubation in hyperosmolar solutions containing mannose or sucrose for 6 h, impaired relaxations to field stimulation, but not to SNP or NO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7582450

Chronic treatment with 13-cis-retinoic acid changes aggressive behaviours in the resident-intruder paradigm in rats.

PubMed

Trent, Simon; Drew, Cheney J G; Mitchell, Paul J; Bailey, Sarah J

2009-12-01

Retinoids, vitamin A related compounds, have an established role in the development of the nervous system and are increasingly recognized to play a role in adult brain function. The synthetic retinoid, 13-cis-retinoic acid (13-cis-RA, Roaccutane) is widely used to treat severe acne but has been linked to an increased risk of neuropsychiatric side effects, including depression. Here we report that chronic administration with 13-cis-RA (1 mg/kg i.p. daily, 7-14 days) in adult rats reduced aggression- and increased flight-related behaviours in the resident-intruder paradigm. However, in the forced swim, sucrose consumption and open field tests treatment for up to 6 weeks with 13-cis-RA did not modify behaviour in adult or juvenile animals. The behavioural change observed in the resident-intruder paradigm is directly opposite to that observed with chronic antidepressant administration. These findings indicate that when a suitably sensitive behavioural test is employed then chronic administration of 13-cis-RA in adult rats induces behavioural changes consistent with a pro-depressant action.

A bio-telemetric device for measurement of left ventricular pressure-volume loops using the admittance technique in conscious, ambulatory rats.

PubMed

Raghavan, Karthik; Feldman, Marc D; Porterfield, John E; Larson, Erik R; Jenkins, J Travis; Escobedo, Daniel; Pearce, John A; Valvano, Jonathan W

2011-06-01

This paper presents the design, construction and testing of a device to measure pressure-volume loops in the left ventricle of conscious, ambulatory rats. Pressure is measured with a standard sensor, but volume is derived from data collected from a tetrapolar electrode catheter using a novel admittance technique. There are two main advantages of the admittance technique to measure volume. First, the contribution from the adjacent muscle can be instantaneously removed. Second, the admittance technique incorporates the nonlinear relationship between the electric field generated by the catheter and the blood volume. A low power instrument weighing 27 g was designed, which takes pressure-volume loops every 2 min and runs for 24 h. Pressure-volume data are transmitted wirelessly to a base station. The device was first validated on 13 rats with an acute preparation with 2D echocardiography used to measure true volume. From an accuracy standpoint, the admittance technique is superior to both the conductance technique calibrated with hypertonic saline injections, and calibrated with cuvettes. The device was then tested on six rats with 24 h chronic preparation. Stability of animal preparation and careful calibration are important factors affecting the success of the device.

Bio-telemetric device for measurement of left ventricular pressure-volume loops using the admittance technique in conscious, ambulatory rats

PubMed Central

Raghavan, Karthik; Feldman, Marc D; Porterfield, John E; Larson, Erik R; Jenkins, J Travis; Escobedo, Daniel; Pearce, John A

2011-01-01

This paper presents the design, construction and testing of a device to measure pressure volume loops in the left ventricle of conscious, ambulatory rats. Pressure is measured with a standard sensor, but volume is derived from data collected from a tetrapolar electrode catheter using a novel admittance technique. There are two main advantages of the admittance technique to measure volume. First, the contribution from the adjacent muscle can be instantaneously removed. Second, the admittance technique incorporates the nonlinear relationship between the electric field generated by the catheter and the blood volume. A low power instrument weighing 27 g was designed, which takes pressure-volume loops every 2 minutes and runs for 24 hours. Pressure-volume data are transmitted wirelessly to a base station. The device was first validated in thirteen rats with an acute preparation with 2-D echocardiography used to measure true volume. From an accuracy standpoint, the admittance technique is superior to both the conductance technique calibrated with hypertonic saline injections, and calibrated with cuvettes. The device was then tested in six rats with a 24-hour chronic preparation. Stability of the animal preparation and careful calibration are important factors affecting the success of the device. PMID:21606560

Attenuation of cadmium-induced decline in spatial, habituation and recognition memory by long-term administration of almond and walnut supplementation: Role of cholinergic function.

PubMed

Batool, Zehra; Agha, Faiza; Ahmad, Saara; Liaquat, Laraib; Tabassum, Saiqa; Khaliq, Saima; Anis, Lubna; Sajid, Irfan; Emad, Shaista; Perveen, Tahira; Haider, Saida

2017-01-01

Excessive exposure of cadmium which is regarded as a neurotoxin can stimulate aging process by inducing abnormality in neuronal function. It has been reported that supplementation of almond and walnut attenuate age-related memory loss. Present study was designed to investigate the weekly administration of cadmium for one month on learning and memory function with relation to cholinergic activity. Cadmium was administered at the dose of 50 mg/kg/week. Whereas, almond and walnut was supplemented at the dose of 400 mg/kg/day along with cadmium administration to separate set of rats. At the end of experiment, memory function was assessed by Morris water maze, open field test and novel object recognition test. Results of the present study showed that cadmium administration significantly reduced memory retention. Reduced acetylcholine levels and elevated acetyl cholinesterase activity were also observed in frontal cortex and hippocampus of cadmium treated rats. Malondialdehyde levels were also significantly increased following the administration of cadmium. Daily supplementation of almond and walnut for 28 days significantly attenuated cadmium-induced memory impairment in rats. Results of the present study are discussed in term of cholinergic activity in cadmium-induced memory loss and its attenuation by nuts supplementation in rats.

Human recombinant erythropoietin reduces sensorimotor dysfunction and cognitive impairment in rat models of chronic kidney disease.

PubMed

Reza-Zaldívar, E E; Sandoval-Avila, S; Gutiérrez-Mercado, Y K; Vázquez-Méndez, E; Canales-Aguirre, A A; Esquivel-Solís, H; Gómez-Pinedo, U; Márquez-Aguirre, A L

2017-11-10

Chronic kidney disease (CKD) can cause anaemia and neurological disorders. Recombinant human erythropoietin (rHuEPO) is used to manage anaemia in CKD. However, there is little evidence on the effects of rHuEPO on behaviour and cognitive function in CKD. This study aimed to evaluate the impact of rHuEPO in sensorimotor and cognitive functions in a CKD model. Male Wistar rats were randomly assigned to 4 groups: control and CKD, with and without rHuEPO treatment (1050 IU per kg body weight, once weekly for 4 weeks). The Morris water maze, open field, and adhesive removal tests were performed simultaneously to kidney damage induction and treatment. Markers of anaemia and renal function were measured at the end of the study. Treatment with rHuEPO reduced kidney damage and corrected anaemia in rats with CKD. We observed reduced sensorimotor dysfunction in animals with CKD and treated with rHuEPO. These rats also completed the water maze test in a shorter time than the control groups. rHuEPO reduces kidney damage, corrects anemia, and reduces sensorimotor and cognitive dysfunction in animals with CKD. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Antidepressant-like effects of mild hypoxia preconditioning in the learned helplessness model in rats.

PubMed

Rybnikova, Elena; Mironova, Vera; Pivina, Svetlana; Tulkova, Ekaterina; Ordyan, Natalia; Vataeva, Ludmila; Vershinina, Elena; Abritalin, Eugeny; Kolchev, Alexandr; Nalivaeva, Natalia; Turner, Anthony J; Samoilov, Michail

2007-05-07

The effects of preconditioning using mild repetitive hypobaric hypoxia (360 Torr for 2 h each of 3 days) have been studied in the learned helplessness model of depression in rats. Male Wistar rats displayed persistent depressive symptoms (depressive-like behaviour in open field, increased anxiety levels in elevated plus maze, ahedonia, elevated plasma glucocorticoids and impaired dexamethasone test) following the exposure to unpredictable and inescapable footshock in the learned helplessness paradigm. Antidepressant treatment (ludiomil, 5 mg/kg i.p.) augmented the development of the depressive state. The hypoxic preconditioning had a clear antidepressive action returning the behavioural and hormonal parameters to the control values and was equally effective in terms of our study as the antidepressant. The findings suggest hypoxic preconditioning as an effective tool for the prophylaxis of post-stress affective pathologies in humans.

Identification of phlebotomine sand fly blood meals by real-time PCR.

PubMed

Sales, Kamila Gaudêncio da Silva; Costa, Pietra Lemos; de Morais, Rayana Carla Silva; Otranto, Domenico; Brandão-Filho, Sinval Pinto; Cavalcanti, Milena de Paiva; Dantas-Torres, Filipe

2015-04-16

Phlebotomine sand flies are blood-feeding insects of great medical and veterinary significance acting as vectors of Leishmania parasites. Studying the blood-feeding pattern of these insects may help in the understanding of their interactions with potential reservoir hosts of Leishmania parasites. In this study, we developed real time PCR assays for the identification of sand fly blood meal. Six pairs of primers were designed based on cytochrome b gene sequences available in GenBank of the following potential hosts: dog, cat, horse, chicken, black rat, and human. Firstly, SYBR Green-based real time PCR assays were conducted using a standard curve with eight different concentrations (i.e., 10 ng, 1 ng, 100 pg, 10 pg, 1 pg, 100 fg, 10 fg and 1 fg per 2 μl) of DNA samples extracted from EDTA blood samples from each target animal. Then, DNA samples extracted from field-collected engorged female sand flies belonging to three species (i.e., Lutzomyia longipalpis, L. migonei and L. lenti) were tested by the protocols standardized herein. Additionally, female sand flies were experimentally fed on a black rat (Rattus rattus) and used for evaluating the time course of the detection of the protocol targeting this species. The protocols performed well with detection limits of 10 pg to 100 fg. Field-collected female sand flies were fed on blood from humans (73%), chickens (23%), dogs (22%), horses (15%), black rats (11%) and cats (2%). Interestingly, 76.1% of the L. longipalpis females were positive for human blood. In total, 48% of the tested females were fed on single sources, 31% on two and 12% on three. The analysis of the time course showed that the real time PCR protocol targeting the black rat DNA was able to detect small amounts of the host DNA up to 5 days after the blood meal. The real time PCR assays standardized herein successfully detected small amounts of host DNA in female sand flies fed on different vertebrate species and, specifically for the black rats, up to 5 days after the blood meal. These assays represent promising tools for the identification of blood meal in field-collected female sand flies.

Rat Phantom Depth Dose Studies in Electron, X-ray, Gamma-Ray, and Reactor Radiation Fields

DTIC Science & Technology

1986-12-01

i©™D©/^ ^1[P@^T Rat phantom depth dose studies in electron , Xrayf gamma-ray, and reactor radiation fields M. Dooley D. M. Eagleson G. H. Zeman...energy electrons , bremsstrahlung, and mixed neutron/gamma radiation fields are sometimes used in radiobiological experiments employing rats. This report...have revealed differing sensitivities of experimental animals that have been exposed to cobalt-60 photons, high-energy electrons , high-energy X rays

The effects of heavy particle irradiation on exploration and response to environmental change

NASA Astrophysics Data System (ADS)

Casadesus, G.; Shukitt-Hale, B.; Cantuti-Castelvetri, I.; Rabin, B.; Joseph, J.

Free radicals produced by exposure to heavy particles have been found to produce motor and behavioral toxicity effects in rats similar to those found during aging. The present research was designed to investigate the effects of exposure to 56Fe particles on the ability to detect novel arrangements in a given environment of male Sprague-Dawley rats. Using a test of spatial memory previously demonstrated to be sensitive to aging, open-field activity and reaction to spatial and non-spatial changes were measured in a group that received a dose of 1.5 Gy (n=10) of 56Fe heavy particle radiation or in non- radiated controls. Animals irradiated with 1.5 Gy of56Fe particles exhibited some age-like effects in animals tested, even though they were for the most part, subtle. Animals took longer to enter, visited less and spent significantly less time in the middle and the center portions of the open-field independently of total frequency and duration of activity of both groups. Likewise, irradiated subjects reacted significantly more to novel objects placed in the open-field than did controls. However, irradiated subjects did not vary from controls in their exploration patterns when objects in the open-field were spatially rearranged. Thus, irradiation with a dose of 1.5 Gy of 56Fe high-energy particle radiation elicited age-like effects in general open-field exploratory behavior, but did not elicit age- like effects during the spatial and non-spatial rearrangement tasks. Supported by N.A.S.A. Grant NAG9-1190.

5,7-Dimethoxycoumarin prevents chronic mild stress induced depression in rats through increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

PubMed

Yang, Wei; Wang, Huanlin

2018-02-01

The current study was aimed to investigate the role of 5,7-dimethoxycoumarin in the prevention of chronic mild stress induced depression in rats. The chronic mild stress rat model was prepared using the known protocols. The results from open-field test showed that rats in the chronic mild stress group scored very low in terms of crossings and rearings than those of the normal rats. However, pre-treatment of the rats with 10 mg/kg doses of 5,7-dimethoxycoumarin prevented decline in the locomotor activity by chronic mild stress. The level of monoamine oxidase-A in the chronic mild stress rat hippocampus was markedly higher. Chronic mild stress induced increase in the monoamine oxidase-A level was inhibited by pre-treatment with 10 mg/kg doses of 5,7-dimethoxycoumarin in the rats. Chronic mild stress caused a marked increase in the level of caspase-3 mRNA and proteins in rat hippocampus tissues. The increased level of caspase-3 mRNA and protein level was inhibited by treatment of rats with 5,7-dimethoxycoumarin (10 mg/kg). 5,7-Dimethoxycoumarin administration into the rats caused a marked increase in the levels of heat shock protein-70 mRNA and protein. The levels of heat shock protein-70 were markedly lower both in normal and chronic mild stress groups of rats compared to the 5,7-dimethoxycoumarin treated groups. Thus 5,7-dimethoxycoumarin prevented the chronic mild stress induced depression in rats through an increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

The probiotic Bifidobacterium infantis 35624 displays visceral antinociceptive effects in the rat.

PubMed

McKernan, D P; Fitzgerald, P; Dinan, T G; Cryan, J F

2010-09-01

Irritable bowel syndrome (IBS) is characterized by recurrent abdominal pain and altering bowel habit with a high percentage of patients displaying comorbid anxiety. Growing clinical and preclinical evidence suggests that probiotic agents may restore the altered brain-gut communication in IBS. In this study, we evaluated the efficacy of repeated treatment with three different probiotics in reducing visceral pain in visceral normosensitive (Sprague-Dawley [SD]) and visceral hypersensitive (Wistar-Kyoto [WKY]) rat strains. Following 14 days oral gavage of Lactobacillus salivarius UCC118, Bifidobacterium infantis 35624, or Bifidobacterium breve UCC2003 both SD and WKY rats were exposed to a novel stress, the open field arena and their behavior was recorded. Subsequently, the effects of probiotics on visceral nociceptive responses were analyzed by recording pain behaviors during colorectal distension (CRD). It was found that there was a difference in the open field behavior between strains but none of the probiotic treatment altered behavior within each strain. Interestingly, the probiotic B. infantis 35624 but not others tested significantly reduced CRD-induced visceral pain behaviors in both rat strains. It significantly increased the threshold pressure of the first pain behavior and also reduced the total number pain behaviors during CRD. These data confirm that probiotics such as B. infantis 35624 are effective in reducing visceral pain and may be effective in treating certain symptoms of IBS.

Orally administered whole egg demonstrates antidepressant-like effects in the forced swimming test on rats.

PubMed

Nagasawa, Mao; Otsuka, Tsuyoshi; Ogino, Yumi; Yoshida, Junki; Tomonaga, Shozo; Yasuo, Shinobu; Furuse, Mitsuhiro

2014-08-01

Several studies have reported that vegetarian diets are associated with a higher prevalence of major depression. Therefore, we hypothesised that the consumption of animal products, especially eggs, may have positive effects on mental health, especially on major depression, because a previous study reported that egg consumption produces numerous beneficial effects in humans. The purpose of the present study was to evaluate the effects of chronic whole-egg treatment on depression-like behaviours in Wistar rats, a control strain, and Wistar Kyoto rats, an animal model of depression. In both the rats, either whole-egg solution (5 ml/kg) or distilled water (5 ml/kg) was orally administrated for 35 days. During these periods, the open-field test (OFT) was conducted on the 21st day, and a forced swimming test (FST) was enforced on the 27th and 28th days. On the 36th day, the plasma and brain were collected. Chronic whole-egg treatment did not affect line crossing in the OFT, whereas it reduced the total duration of immobility in the FST on both strains. Furthermore, interestingly, the results indicated the possibility that whole-egg treatment elevated the incorporation of tryptophan into the brain, and the tryptophan concentration in the prefrontal cortex was actually increased by the treatment. This study demonstrated that whole-egg treatment exerts an antidepressant-like effect in the FST. It is suggested that whole egg may be an excellent food for preventing and alleviating the conditions of major depression.

The Effect of TIMP-1 on the Cone Mosaic in the Retina of the Rat Model of Retinitis Pigmentosa

PubMed Central

Ji, Yerina; Yu, Wan-Qing; Eom, Yun Sung; Bruce, Farouk; Craft, Cheryl Mae; Grzywacz, Norberto M.; Lee, Eun-Jin

2015-01-01

Purpose. The array of photoreceptors found in normal retinas provides uniform and regular sampling of the visual space. In contrast, cones in retinas of the S334ter-line-3 rat model for RP migrate to form a mosaic of rings, leaving large holes with few or no photoreceptors. Similar mosaics appear in human patients with other forms of retinal dystrophy. In the current study, we aimed to investigate the effect of tissue inhibitor of metalloproteinase-1 (TIMP-1) on the mosaic of cones in S334ter-line-3 rat retinas. We focused on TIMP-1 because it is one of the regulators of the extracellular matrix important for cellular migration. Methods. Immunohistochemistry was performed to reveal M-opsin cone cells (M-cone) and the results were quantified to test statistically whether or not TIMP-1 restores the mosaics to normal. In particular, the tests focused on the Voronoi and nearest-neighbor distance analyses. Results. Our tests indicated that TIMP-1 led to significant disruption of the M-opsin cone rings in S334ter-line-3 rat retinas and resulted in almost complete homogeneous mosaics. In addition, TIMP-1 induced the M-cone spatial distribution to become closer to random with decreased regularity in S334ter-line-3 rat retinas. Conclusions. These findings confirm that TIMP-1 induced M-cone mosaics in S334ter-line-3 to gain homogeneity without reaching the degree of regularity seen in normal retinal mosaics. Even if TIMP-1 fails to promote regularity, the effects of this drug on homogeneity appear to be so dramatic that TIMP-1 may be a potential therapeutic agent. TIMP-1 improves sampling of the visual field simply by causing homogeneity. PMID:25515575

Effects of experimental suppression of active (REM) sleep during early development upon adult brain and behavior in the rat.

PubMed

Mirmiran, M; Scholtens, J; van de Poll, N E; Uylings, H B; van der Gugten, J; Boer, G J

1983-04-01

In order to test the hypothesis that active sleep (AS) is important for the normal development of the central nervous system, 3 different deprivation methods were applied to male Wistar rat pups during the first month of life. Daily injection of clomipramine from 8 to 21 days of age reduced the high level of AS to less than the adult value throughout most of the experimental period. Administration of clonidine from 8 to 21 days of life induced an almost total suppression of AS. Instrumental deprivation, using the 'pendulum' method, led to a significant (but less severe) AS reduction during 2-4 weeks of postnatal age. Open-field behavior testing in adulthood revealed a higher than normal level of ambulation in all 3 experimental groups. Masculine sexual responses were deficient, due to a low level of both mounts and ejaculations, in both clomipramine- and clonidine-treated animals. Neither passive avoidance learning nor dark preference tests revealed any differences between the experimental and control rats. Sleep observations showed that there was an abnormally high incidence of large myoclonic jerks during AS in both clomipramine- and clonidine-treated rats. Subsequent measurement of regional brain weights showed a significant reduction in the cerebral cortex and medulla oblongata, as compared with the respective control groups, in both the clomipramine- and the clonidine-treated rats. In addition, DNA and protein determination in the affected brain areas showed a proportional reduction in the cortex and in the medulla. These results demonstrate that interference with normal functioning either of AS per se or of specific monoaminergic transmitter systems during early development can produce long-lasting behavioral as well as brain morphological and biochemical abnormalities in later life.

Engaging in paced mating, but neither exploratory, anti-anxiety, nor social behavior, increases 5α-reduced progestin concentrations in midbrain, hippocampus, striatum, and cortex

PubMed Central

Frye, Cheryl A; Paris, Jason J; Rhodes, Madeline E

2010-01-01

Sequential actions of 17β-estradiol (E2) and progesterone (P4) in the hypothalamus and the P4 metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), in the midbrain ventral tegmental area (VTA) respectively mediate the initiation and intensity of lordosis of female rats and mayalso modulate anxiety and social behaviors, through actions in these, and/or other brain regions. Biosynthesis of E2, P4, and 3α,5α-THP can also occur in brain, independent of peripheral gland secretion, in response to environmental/behavioral stimuli. The extent to which engaging in tasks related to reproductive behaviors and/or mating increased E2 or progestin concentrations in brain was investigated. In Experiment 1, proestrous rats were randomly assigned to be tested in individual tasks, including the open field, elevated plus maze, partner preference, social interaction, or no test control, in conjunction with paced mating or no mating. Engaging in paced mating, but not other behaviors, significantly increased dihydroprogesterone (DHP) and 3α,5α-THP levels in midbrain, hippocampus, striatum, and cortex. In Experiment 2, proestrous rats were tested in the combinations of the above tasks (open field and elevated plus maze, partner preference, and social interaction) with or without paced mating. As in Experiment 1, only engaging in paced mating increased DHP and 3α,5α-THP concentrations in midbrain, hippocampus, striatum, and cortex. Thus, paced mating enhances concentrations of 5α-reduced progestins in brain areas associated with reproduction (midbrain), as well as exploration/anxiety (hippocampus and striatum) and social behavior (cortex). PMID:17379660

Estrogen Receptor-β Agonist Diarylpropionitrile: Biological Activities of R- and S-Enantiomers on Behavior and Hormonal Response to Stress

PubMed Central

Weiser, Michael J.; Wu, T. John; Handa, Robert J.

2009-01-01

Estrogens have been shown to have positive and negative effects on anxiety and depressive-like behaviors, perhaps explained by the existence of two distinct estrogen receptor (ER) systems, ERα and ERβ. The ERβ agonist, diarylpropionitrile (DPN) has been shown to have anxiolytic properties in rats. DPN exists as a racemic mixture of two enantiomers, R-DPN and S-DPN. In this study, we compared R-DPN and S-DPN for their in vitro binding affinity, ability to activate transcription in vitro at an estrogen response element, and in vivo endocrine and behavioral responses. In vitro binding studies using recombinant rat ERβ revealed that S-DPN has a severalfold greater relative binding affinity for ERβ than does R-DPN. Furthermore, cotransfection of N-38 immortalized hypothalamic cells with an estrogen response element-luc reporter and ERβ revealed that S-DPN is a potent activator of transcription in vitro, whereas R-DPN is not. Subsequently, we examined anxiety-like behaviors using the open-field test and elevated plus maze or depressive-like behaviors, using the forced swim test. Ovariectomized young adult female Sprague Dawley rats treated with racemic DPN, S-DPN, and the ERβ agonist, WAY-200070, showed significantly decreased anxiety-like behaviors in both the open-field and elevated plus maze and significantly less depressive-like behaviors in the forced swim test compared with vehicle-, R-DPN-, or propylpyrazoletriol (ERα agonist)-treated animals. In concordance with the relative binding affinity and transcriptional potency, these results demonstrate that the S-enantiomer is the biologically active form of DPN. These studies also indicate that estrogen's positive effects on mood, including its anxiolytic and antidepressive actions, are due to its actions at ERβ. PMID:19074580

Impact of maternal mild hyperglycemia on maternal care and offspring development and behavior of Wistar rats.

PubMed

Kiss, Ana Carolina Inhasz; Woodside, Barbara; Felício, Luciano Freitas; Anselmo-Franci, Janete; Damasceno, Débora Cristina

2012-10-10

The aim of the present study was to evaluate the effect of maternal mild hyperglycemia on maternal behavior, as well as the development, behavior, reproductive function, and glucose tolerance of the offspring. At birth, litters were assigned either to Control (subcutaneous (sc)-citrate buffer) or STZ groups (streptozotocin (STZ)-100mg/kg-sc.). On PND 90 both STZ-treated and Control female rats were mated. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed during pregnancy. Pregnancy duration, litter size and sex ratio were assessed. Newborns were classified according to birth weight as small (SPA), adequate (APA), or large for pregnancy age (LPA). Maternal behavior was analyzed on PND 5 and 10. Offspring body weight, length, and anogenital distance were measured and general activity was assessed in the open field. Sexual behavior was tested in both male and female offspring. Levels of reproductive hormones and estrous cycle duration were evaluated in female offspring. Female offspring were mated and both a GTT and ITT performed during pregnancy. Neonatal STZ administration caused mild hyperglycemia during pregnancy and changed some aspects of maternal care. The hyperglycemic intrauterine milieu impaired physical development and increased immobility in the open field in the offspring although the latter effect appeared at different ages for males (adulthood) and females (infancy). There was no impairment in the sexual behavior of either male or female offspring. As adults, female offspring of STZ-treated mothers did not show glucose intolerance during pregnancy. Thus, offspring of female rats that show mild hyperglycemia in pregnancy have fewer behavioral and developmental impairments than previously reported in the offspring of severely diabetic dams suggesting that the degree of impairment is directly related to the mother glycemic intensity. Copyright © 2012 Elsevier Inc. All rights reserved.

Chronic nandrolone decanoate exposure during adolescence affects emotional behavior and monoaminergic neurotransmission in adulthood.

PubMed

Rainer, Quentin; Speziali, Simona; Rubino, Tiziana; Dominguez-Lopez, Sergio; Bambico, Francis Rodriguez; Gobbi, Gabriella; Parolaro, Daniela

2014-08-01

Nandrolone decanoate, an anabolic androgen steroid (AAS) illicitly used by adult and adolescent athletes to enhance physical performance and body image, induces psychiatric side effects, such as aggression, depression as well as a spectrum of adverse physiological impairments. Since adolescence represents a neurodevelopmental window that is extremely sensitive to the detrimental effects of drug abuse, we investigated the long-term behavioral and neurophysiological consequences of nandrolone abuse during adolescence. Adolescent rats received daily injections of nandrolone decanoate (15 mg/kg, i.m.) for 14 days (PND 40-53). At early adulthood (PND 68), forced swim, sucrose preference, open field and elevated plus maze tests were performed to assess behavioral changes. In vivo electrophysiological recordings were carried out to monitor changes in electrical activity of serotonergic neurons of the dorsal raphe nucleus (DRN) and noradrenergic neurons of the locus coeruleus (LC). Our results show that after early exposure to nandrolone, rats display depression-related behavior, characterized by increased immobility in the forced swim test and reduced sucrose intake in the sucrose preference test. In addition, adult rats presented anxiety-like behavior characterized by decreased time and number of entries in the central zone of the open field and decreased time spent in the open arms of the elevated plus maze. Nandrolone decreased the firing rate of spontaneously active serotonergic neurons in the DRN while increasing the firing rate of noradrenergic neurons in the LC. These results provide evidence that nandrolone decanoate exposure during adolescence alters the emotional profile of animals in adulthood and significantly modifies both serotonergic and noradrenergic neurotransmission. Copyright © 2014 Elsevier Ltd. All rights reserved.

Risk-assessment and risk-taking behavior predict potassium- and amphetamine-induced dopamine response in the dorsal striatum of rats

PubMed Central

Palm, Sara; Momeni, Shima; Lundberg, Stina; Nylander, Ingrid; Roman, Erika

2014-01-01

Certain personality types and behavioral traits display high correlations to drug use and an increased level of dopamine in the reward system is a common denominator of all drugs of abuse. Dopamine response to drugs has been suggested to correlate with some of these personality types and to be a key factor influencing the predisposition to addiction. This study investigated if behavioral traits can be related to potassium- and amphetamine-induced dopamine response in the dorsal striatum, an area hypothesized to be involved in the shift from drug use to addiction. The open field and multivariate concentric square field™ tests were used to assess individual behavior in male Wistar rats. Chronoamperometric recordings were then made to study the potassium- and amphetamine-induced dopamine response in vivo. A classification based on risk-taking behavior in the open field was used for further comparisons. Risk-taking behavior was correlated between the behavioral tests and high risk takers displayed a more pronounced response to the dopamine uptake blocking effects of amphetamine. Behavioral parameters from both tests could also predict potassium- and amphetamine-induced dopamine responses showing a correlation between neurochemistry and behavior in risk-assessment and risk-taking parameters. In conclusion, the high risk-taking rats showed a more pronounced reduction of dopamine uptake in the dorsal striatum after amphetamine indicating that this area may contribute to the sensitivity of these animals to psychostimulants and proneness to addiction. Further, inherent dopamine activity was related to risk-assessment behavior, which may be of importance for decision-making and inhibitory control, key components in addiction. PMID:25076877

High novelty-seeking rats are resilient to negative physiological effects of the early life stress.

PubMed

Clinton, Sarah M; Watson, Stanley J; Akil, Huda

2014-01-01

Exposure to early life stress dramatically impacts adult behavior, physiology, and neuroendocrine function. Using rats bred for novelty-seeking differences and known to display divergent anxiety, depression, and stress vulnerability, we examined the interaction between early life adversity and genetic predisposition for high- versus low-emotional reactivity. Thus, bred Low Novelty Responder (bLR) rats, which naturally exhibit high anxiety- and depression-like behavior, and bred High Novelty Responder (bHR) rats, which show low anxiety/depression together with elevated aggression, impulsivity, and addictive behavior, were subjected to daily 3 h maternal separation (MS) stress postnatal days 1-14. We hypothesized that MS stress would differentially impact adult bHR/bLR behavior, physiology (stress-induced defecation), and neuroendocrine reactivity. While MS stress did not impact bHR and bLR anxiety-like behavior in the open field test and elevated plus maze, it exacerbated bLRs' already high physiological response to stress - stress-induced defecation. In both tests, MS bLR adult offspring showed exaggerated stress-induced defecation compared to bLR controls while bHR offspring were unaffected. MS also selectively impacted bLRs' (but not bHRs') neuroendocrine stress reactivity, producing an exaggerated corticosterone acute stress response in MS bLR versus control bLR rats. These findings highlight how genetic predisposition shapes individuals' response to early life stress. Future work will explore neural mechanisms underlying the distinct behavioral and neuroendocrine consequences of MS in bHR/bLR animals.

Spatial learning, monoamines and oxidative stress in rats exposed to 900 MHz electromagnetic field in combination with iron overload.

PubMed

Maaroufi, Karima; Had-Aissouni, Laurence; Melon, Christophe; Sakly, Mohsen; Abdelmelek, Hafedh; Poucet, Bruno; Save, Etienne

2014-01-01

The increasing use of mobile phone technology over the last decade raises concerns about the impact of high frequency electromagnetic fields (EMF) on health. More recently, a link between EMF, iron overload in the brain and neurodegenerative disorders including Parkinson's and Alzheimer's diseases has been suggested. Co-exposure to EMF and brain iron overload may have a greater impact on brain tissues and cognitive processes than each treatment by itself. To examine this hypothesis, Long-Evans rats submitted to 900 MHz exposure or combined 900 MHz EMF and iron overload treatments were tested in various spatial learning tasks (navigation task in the Morris water maze, working memory task in the radial-arm maze, and object exploration task involving spatial and non spatial processing). Biogenic monoamines and metabolites (dopamine, serotonin) and oxidative stress were measured. Rats exposed to EMF were impaired in the object exploration task but not in the navigation and working memory tasks. They also showed alterations of monoamine content in several brain areas but mainly in the hippocampus. Rats that received combined treatment did not show greater behavioral and neurochemical deficits than EMF-exposed rats. None of the two treatments produced global oxidative stress. These results show that there is an impact of EMF on the brain and cognitive processes but this impact is revealed only in a task exploiting spontaneous exploratory activity. In contrast, there are no synergistic effects between EMF and a high content of iron in the brain. Copyright © 2013 Elsevier B.V. All rights reserved.

[Influence of low frequency magnetic field used in magnetotherapy on interleukin 6 (IL-6) contents in rat heart and brain].

PubMed

Ciejka, Elżbieta; Skibska, Beata; Gorąca, Anna

2017-06-27

The human population is exposed ever more frequently to magnetic fields (MF). This is due to both technological progress and development of the economy as well as to advances made in medical science. That is why the thorough understanding and systematized knowledge about mechanisms by which MF exerts its effects on living organisms play such an important role. In this context the health of MF-exposed people is the subject of particular concern. The aim of the study was to evaluate the effect of extremely low frequency magnetic field (ELFMF) used in magnetotherapy on the concentration of interleukin 6 (IL-6) in rat heart and brain. The male rats were randomly divided into 3 experimental groups: group I - control, without contact with magnetic field; group II - exposed to bipolar, rectangular magnetic field 40 Hz, induction "peak-to-peak" 7 mT 30 min/day for 2 weeks; and group III - exposed to bipolar, rectangular magnetic field 40 Hz, 7 mT 60 min/day for 2 weeks. Concentration of IL-6 in the heart and brain of animals was measured after MF exposure. Exposure to ELFMF: 40 Hz, induction "peak-to-peak" 7 mT 30 min/day for 2 weeks caused a significant IL-6 increase in rat hearts compared to the control group (p < 0.05) and a non-significant IL-6 decrease in rat brain. The magnetic field applied for 60 min resulted in non-significant IL-6 increase in rat hearts compared to the control group and significant IL-6 decrease in rat brain (p < 0.05). The influence of magnetic field on inflammation in the body varies depending on the MF parameters and the affected tissues or cells. Med Pr 2017;68(4):517-523. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Effects of the mGluR5 antagonist MPEP on ethanol withdrawal induced anxiety-like syndrome in rats.

PubMed

Kumar, Jaya; Hapidin, Hermizi; Bee, Yvonne-Tee Get; Ismail, Zalina

2013-11-26

Abstinence from chronic ethanol consumption leads to the manifestation of a variety of symptoms attributed to central nervous system hyperexcitability, such as increased irritability, anxiety, and restlessness. Recent studies have demonstrated the importance of metabotropic glutamate receptor 5 (mGluR5) in addictive behaviours. This study investigates the effects of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on ethanol withdrawal induced anxiety using two behavioural paradigms. Male Wistar rats were fed a Modified Liquid Diet (MLD) containing low fat cow milk, sucrose, and maltodextrin with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours into ethanol withdrawal, the rats were intraperitoneally injected with normal saline and MPEP (2.5, 5.0, 10, 20, 30 mg/kg) and were assessed for ethanol withdrawal induced anxiety-like syndrome using an automated elevated plus maze and an open field. MPEP at 10 mg/kg significantly attenuated ethanol withdrawal induced anxiety without any compromising effects on locomotor activities. Despite reversing several indices of ethanol withdrawal induced anxiety in both the elevated plus maze and the open field, low doses of MPEP (2.5, 5 mg/kg) significantly compromised the locomotor activities of ethanol withdrawn rats. High doses of MPEP (20 and 30 mg/kg) significantly attenuated withdrawal anxiety when tested in the elevated plus maze but not in the open field. Administration of MPEP (2.5, 5, 10, 20, 30 mg/kg) has no significant compromising effect on the locomotor activities of ethanol naïve rats. Despite significantly reducing withdrawal anxiety in both behavioural paradigms at 10 mg/kg, the compromising effects of low and high doses of MPEP must be further explored along with the therapeutic efficiency of this drug for relieving withdrawal induced anxiety.

Effects of the mGluR5 antagonist MPEP on ethanol withdrawal induced anxiety-like syndrome in rats

PubMed Central

2013-01-01

Abstinence from chronic ethanol consumption leads to the manifestation of a variety of symptoms attributed to central nervous system hyperexcitability, such as increased irritability, anxiety, and restlessness. Recent studies have demonstrated the importance of metabotropic glutamate receptor 5 (mGluR5) in addictive behaviours. This study investigates the effects of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on ethanol withdrawal induced anxiety using two behavioural paradigms. Male Wistar rats were fed a Modified Liquid Diet (MLD) containing low fat cow milk, sucrose, and maltodextrin with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours into ethanol withdrawal, the rats were intraperitoneally injected with normal saline and MPEP (2.5, 5.0, 10, 20, 30 mg/kg) and were assessed for ethanol withdrawal induced anxiety-like syndrome using an automated elevated plus maze and an open field. MPEP at 10 mg/kg significantly attenuated ethanol withdrawal induced anxiety without any compromising effects on locomotor activities. Despite reversing several indices of ethanol withdrawal induced anxiety in both the elevated plus maze and the open field, low doses of MPEP (2.5, 5 mg/kg) significantly compromised the locomotor activities of ethanol withdrawn rats. High doses of MPEP (20 and 30 mg/kg) significantly attenuated withdrawal anxiety when tested in the elevated plus maze but not in the open field. Administration of MPEP (2.5, 5, 10, 20, 30 mg/kg) has no significant compromising effect on the locomotor activities of ethanol naïve rats. Despite significantly reducing withdrawal anxiety in both behavioural paradigms at 10 mg/kg, the compromising effects of low and high doses of MPEP must be further explored along with the therapeutic efficiency of this drug for relieving withdrawal induced anxiety. PMID:24279870

Electric and magnetic fields and tumor progression. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keng, P.C.; Grota, L.J.; Michaelson, S.

This laboratory study has rigorously investigated two previously reported biological effects of 60-Hz electric and magnetic fields. The first effect involves nighttime suppression of melatonin synthesis in the pineal glands of rats exposed to high electric fields. The second concerns the increase in colony forming ability of human colon cancer cells exposed to 1.4-G magnetic fields. Neither effect was detected in the present study. A series of published laboratory studies on rats reported that 60-Hz electric fields at various field levels up to 130 kV/m suppress the nighttime synthesis of melatonin, a hormone produced by the pineal gland. Since melatoninmore » is known to modulate the immune system and may inhibit cancer cell activity, changes in physiological levels of melatonin may have significant health consequences. In the repeat experiments, field exposure did not alter nighttime levels of melatonin or enzyme activities in the pineal gland. A small but statistically significant reduction of about 20% in serum melatonin was seen in exposed animals. Pineal melatonin was also unaffected by the presence of red light as a cofactor with field exposure or by time-shifting the daily field exposure period. Another study reported that 60-Hz magnetic fields can affect the colony forming ability of human cancer cells after exposure in a culture medium. In the repeat experiments, field exposure did not alter the colony forming ability of human Colo 205 cells in two different cell concentrations at plating or in two different incubation conditions. Field exposure also did not affect cell cycling in any of the four cell lines tested.« less

The effects of N-Methyl-D-Aspartate receptor blockade during the early neurodevelopmental period on emotional behaviors and cognitive functions of adolescent Wistar rats.

PubMed

Kocahan, Sayad; Akillioglu, Kubra; Binokay, Secil; Sencar, Leman; Polat, Sait

2013-05-01

The N-Methyl-D-Aspartate (NMDA) receptor is expressed abundantly in the brain and plays an important role in neuronal development, learning and memory, neurodegenerative diseases, and neurogenesis. In this study, we evaluated the effects of NMDA receptor blockade during the early neurodevelopmental period on exploratory locomotion, anxiety-like behaviors and cognitive functions of adolescent Wistar rats. NMDA receptor hypofunction was induced 7-10 days after birth using MK-801 in rats (0.25 mg/kg twice a day for 4 days via intraperitoneal injection). The open-field (OF), elevated plus maze (EPM) and passive avoidance (PA) tests were used to evaluate exploratory locomotion, anxiety-like behaviors and cognitive functions. In the OF test, MK-801 caused an increase in locomotion behavior (p < 0.01) and in the frequency of rearing (p < 0.05). In the EPM test, MK-801 treatment increased the time spent in the open arms, the number of open arm entries and the amount of head dipping (p < 0.01). MK-801 treatment caused no statistical difference compared to the control group in the PA test (p > 0.05). Chronic NMDA receptor blockade during the critical period of maturation for the glutamatergic brain system (postnatal days 7-10) produces locomotor hyperactivity and decreased anxiety levels, but has no significant main effect on cognitive function during adolescence.

False context fear memory in rats.

PubMed

Bae, Sarah E; Holmes, Nathan M; Westbrook, R Frederick

2015-10-01

Four experiments used rats to study false context fear memories. In Experiment 1, rats were pre-exposed to a distinctive chamber (context A) or to a control environment (context C), shocked after a delay in a second chamber (context B) and tested either in B or A. Rats pre-exposed to A froze just as much as control rats in B but more than control rats in A. In Experiment 2, rats were pre-exposed to A or C, subjected to an immediate shock in B and tested in B or A. Rats pre-exposed to A froze when tested in A but did not freeze when tested in B and control rats did not freeze in either A or B. The false fear memory to the pre-exposed A was contingent on its similarity with the shocked B. In Experiment 3, rats pre-exposed to A and subjected to immediate shock in B froze when tested in A but did not freeze when tested in C and rats pre-exposed to C did not freeze when tested either in A or C. In Experiment 4, rats pre-exposed to A and subjected to immediate shock in B froze more when tested in A than rats whose pre-exposure to A began with an immediate shock. The results were discussed in terms of a dual systems explanation of context fear conditioning: a hippocampal-dependent process that forms a unitary representation of context and an amygdala-based process which associates this representation with shock. © 2015 Bae et al.; Published by Cold Spring Harbor Laboratory Press.

Place and Response Learning in the Open-field Tower Maze.

PubMed

Lipatova, Olga; Campolattaro, Matthew M; Toufexis, Donna J; Mabry, Erin A

2015-10-28

This protocol describes how the Open-field Tower Maze (OFTM) paradigm is used to study spatial learning in rodents. This maze is especially useful for examining how rats learn to use a place- or response-learning to successfully navigate in an open-field arena. Additionally, this protocol describes how the OFTM differs from other behavioral maze paradigms that are commonly used to study spatial learning in rodents. The OFTM described in this article was adapted from the one previously described by Cole, Clipperton, and Walt (2007). Specifically, the OFTM was created to test spatial learning in rodents without the experimenter having to consider how "stress" might play a role as a confounding variable. Experiments have shown that stress-alone can significantly affect cognitive function(1). The representative results section contains data from an experiment that used the OFTM to examine the effects of estradiol treatment on place- and response-learning in adult female Sprague Dawley rats(2). Future studies will be designed to examine the role of the hippocampus and striatum in place- and response-learning in the OFTM.

Comparison of the validity of the use of the spontaneously hypertensive rat as a model of attention deficit hyperactivity disorder in males and females.

PubMed

Bayless, Daniel W; Perez, Maria C; Daniel, Jill M

2015-06-01

The spontaneously hypertensive rat (SHR) is a commonly used and well-studied rodent model of attention deficit hyperactivity disorder (ADHD). Sex differences in the cognitive symptoms of ADHD are reported. However, the female SHR rat is much less studied than its male counterpart. The goal of the current study was to assess the validity of the SHR rodent model of ADHD by examining attentional performance, inhibitory control, and hyperactivity in both male and female SHR rats. Adult SHR and control Wistar-Kyoto rats were trained on the 5-choice serial reaction time task, a self-paced test of attention and inhibitory control. This task requires animals to identify the location of a brief light stimulus among five possible locations under several challenging conditions. Analyses of percent correct revealed that attentional performance in SHR females was not significantly different from control females, whereas attentional performance in SHR males was significantly different from control males. Analyses of the number of premature responses revealed that SHR rats made more inhibitory control errors than did control rats and that this decrease in inhibitory control was present in both SHR males and females. Analyses of activity in the open field revealed that SHR rats were more hyperactive than were control rats and that this increased hyperactivity was present in both SHR males and females. The current findings have implications for the study of sex differences in ADHD and for the use of SHR rats as a model of ADHD in females. Copyright © 2015 Elsevier B.V. All rights reserved.

NASA Rat Acoustic Tolerance Test 1994-1995: 8 kHz, 16 kHz, 32 kHz Experiments

NASA Technical Reports Server (NTRS)

Mele, Gary D.; Holley, Daniel C.; Naidu, Sujata

1996-01-01

Adult male Sprague-Dawley rats were exposed to chronic applied sound (74 to 79 dB, SPL) with octave band center frequencies of either 8, 16 or 32 kHz for up to 60 days. Control cages had ambient sound levels of about 62 dB (SPL). Groups of rats (test vs. control; N=9 per group) were euthanized after 0. 5. 14, 30, and 60 days. On each euthanasia day, objective evaluation of their physiology and behavior was performed using a Stress Assessment Battery (SAB) of measures. In addition, rat hearing was assessed using the brain stem auditory evoked potential (BAER) method after 60 days of exposure. No statistically significant differences in mean daily food use could be attributed to the presence of the applied test sound. Test rats used 5% more water than control rats. In the 8 kHz and 32 kHz tests this amount was statistically significant(P less than .05). This is a minor difference of questionable physiological significance. However, it may be an indication of a small reaction to the constant applied sound. Across all test frequencies, day 5 test rats had 6% larger spleens than control rats. No other body or organ weight differences were found to be statistically significant with respect to the application of sound. This spleen effect may be a transient adaptive process related to adaptation to the constant applied noise. No significant test effect on differential white blood cell counts could be demonstrated. One group demonstrated a low eosinophil count (16 kHz experiment, day 14 test group). However this was highly suspect. Across all test frequencies studied, day 5 test rats had 17% fewer total leukocytes than day 5 control rats. Sound exposed test rats exhibited 44% lower plasma corticosterone concentrations than did control rats. Note that the plasma corticosterone concentration was lower in the sound exposed test animals than the control animals in every instance (frequency exposure and number of days exposed).

Zeaxanthin improved diabetes-induced anxiety and depression through inhibiting inflammation in hippocampus.

PubMed

Zhou, Xiaoyan; Gan, Tian; Fang, Gaoxia; Wang, Shangshang; Mao, Yizhen; Ying, Changjiang

2018-06-01

It is generally accepted that inflammation plays a key role in anxiety and depression induced by diabetes. However, the underlying mechanism and effective treatment method of these diabetes-associated behavior disorders remain to be determined. In the present study, we attempted to illuminate the implication of zeaxanthin in anxiety, depression and neuroinflammation caused by hyperglycemia, and further elaborate the relevant mechanism under these neuropsychiatric disorders. In the current work, diabetic rats were induced by high glucose and fat diet followed by a single intraperitoneal injection of streptozocin, and zeaxanthin was orally administration every day (From 6th to 19th week). Diabetes-associated anxiety and depression were assessed using open field test (OFT) and Forced swimming test (FST) respectively. Moreover, the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in hippocampus were tested using ELISA and WB. Data showed that long-term zeaxanthin treatment improve diabetic symptoms and alleviate anxiety and depression in diabetic rats. Furthermore, excessive production of IL-6, IL-1β and TNF-α could be reduced with zeaxanthin treatment. In conclusion, we suggested that zeaxanthin can ameliorate diabetes-associated anxiety and depression, inhibit inflammation in diabetic rats. Our results could provide a potential therapeutic approach for the treatment of abnormal behavior induced by hyperglycemia.

Proinflammatory cytokines correlate with early exercise attenuating anxiety-like behavior after cerebral ischemia.

PubMed

Zhang, Qi; Zhang, Jingjun; Yan, Yuzhong; Zhang, Pengyue; Zhang, Wei; Xia, Rong

2017-11-01

Stroke may cause neuropsychiatric problems, which have negative effects on cognitive functions and behavior. Exercise plays an important role in reducing the occurrence and development of stroke, the concrete mechanism is not fully clarified. In this study, we attempted to determine whether early treadmill exercise attenuates anxiety-like behavior by regulation of inflammation after brain ischemia. We subjected adult male rats to middle cerebral artery occlusion (MCAO) for 90 min and trained rats started to run on a treadmill from postoperative day 1 to day 14. The effects of treadmill on cognitive functions, anxiety-like behavior, and immune activation were analyzed by Morris water maze test, open field test, elevated plus maze test, and enzyme-linked immunosorbent assay. Early treadmill exercise significantly improved cognitive function, alleviated anxiety-like behavior in ischemic rats model; this improvement was associated with significantly decreased activation of astrocytes and microglia cells and proinflammatory markers (platelet-activating factor [PAF], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α], intercellular adhesion molecule-1 [ICAM-1], and vascular cell adhesion molecule-1 [VCAM-1]). Our results indicated that early treadmill exercise attenuated anxiety-like behavior by decreasing inflammation response, exercise conferred a great benefit of attenuating anxiety-like behavior via anti-inflammatory treatment may prove to be a novel neuroprotective strategy for stroke.

Catalytic nanomedicine: a new field in antitumor treatment using supported platinum nanoparticles. In vitro DNA degradation and in vivo tests with C6 animal model on Wistar rats.

PubMed

López, T; Figueras, F; Manjarrez, J; Bustos, J; Alvarez, M; Silvestre-Albero, J; Rodríguez-Reinoso, F; Martínez-Ferre, A; Martínez, E

2010-05-01

Novel nanostructured TiO2 and SiO2 based biocatalysts, with 3-4 wt. % of Pt have been developed. The obtained materials exhibit a high surface area together with a broad pore size distribution. The method of synthesis allowed obtaining high dispersed platinum metal nanoparticles. In vitro DNA reactivity test of the biocatalysts were carried out by electrophoresis and formation of DNA adducts was observed. The most active biocatalyst was H2PtCl6/SiO2. These biocatalysts were also tested in an experimental model of C6 brain tumours in Wistar rats. Administration of the material was made by stereotactic brain surgery to place it directly in the malignant tissue. A significant decrease in tumour size and weight as well as morphologic changes in cancer cells were observed. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

Effects of chronic dysthyroidism on activity and exploration.

PubMed

Sala-Roca, Josefina; Martí-Carbonell, Maria Assumpció; Garau, Adriana; Darbra, Sonia; Balada, Ferran

2002-09-01

The aim of the present study was to determine the influence of thyroid function on the activity and exploratory behaviour of male Wistar rats. Dysthyroidism was induced by adding drugs to their drinking water from the ninth day of gestation. This method is not as stressful as daily thyroxine injections or thyroidectomy, and therefore did not affect the analysed behavioural patterns. After weaning, the drugs were administered to the young rats until the end of the experiment. Activity and exploration were measured using the Boissier test, a light-darkness test and an open-field test when they were 77 days old. In order to verify that the animals' motor capacity had not been impaired, a psychomotor battery was used. Chronic hyperthyroidism produced a significant increase in activity, but did not affect exploration. On the other hand, hypothyroidism did not affect activity, but did increase exploration. This increase in exploration was observed in activity-independent behavioural parameters, such as head dipping and glancing. Copyright 2002 Elsevier Science Inc.

Individual differences in the forced swimming test and the effect of environmental enrichment: searching for an interaction.

PubMed

Sequeira-Cordero, A; Mora-Gallegos, A; Cuenca-Berger, P; Fornaguera-Trías, J

2014-04-18

Animals with low and high immobility in the forced swimming test (FST) differ in a number of neurobehavioral factors. A growing body of evidence suggests that the exposure to enriched environments mediates a number of changes in the brain. Therefore, we studied if animals' individuality can somehow modulate the response to environmental stimuli. Male rats were classified according to their immobility time scores in the FST test session as animals with low, medium or high immobility. Then, rats from groups with low and high immobility were randomly distributed in two groups to be reared in different housing conditions (i.e., enriched and standard conditions) during 8weeks. Animals were subjected to the open field test (OFT) before and 6weeks after the start of housing protocol. Rats with high immobility in the FST also showed high ambulation and high rearing time in the first OFT. Such findings were not observed in the second OFT. Conversely, an effect of environmental enrichment was found in the second OFT where enriched animals showed lower ambulation and higher grooming time than the standard control group. Rats were sacrificed after the housing protocol and neurochemical content and/or gene expression were studied in three different brain regions: the prefrontal cortex, the hippocampus and the nucleus accumbens. Rats with low immobility showed significantly higher accumbal 5-HT levels than animals with high immobility, whereas no neurochemical differences were observed between enriched and standard animals. Regarding expression data, however, an effect of enrichment on accumbal corticotropin-releasing factor (CRF) and its receptor 1 (CRFR1) levels was observed, and such effect depended on immobility levels. Thus, our results not only allowed us to identify a number of differences between animals with low and high immobility or animals housed in standard and enriched conditions, but also suggested that animals' individuality modulated in some way the response to environmental stimuli. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

A medicinal herb, Melissa officinalis L. ameliorates depressive-like behavior of rats in the forced swimming test via regulating the serotonergic neurotransmitter.

PubMed

Lin, Shih-Hang; Chou, Mei-Ling; Chen, Wei-Cheng; Lai, Yi-Syuan; Lu, Kuan-Hung; Hao, Cherng-Wei; Sheen, Lee-Yan

2015-12-04

Depression is a serious psychological disorder that causes extreme economic loss and social problems. However, the conventional medications typically cause side effects that result in patients opting to out of therapy. Lemon balm (Melissa officinalis L., MO) is an old and particularly reliable medicinal herb for relieving feelings of melancholy, depression and anxiety. The present study aims to investigate the antidepressant-like activity of water extract of MO (WMO) by evaluating its influence on the behaviors and the relevant neurotransmitters of rats performed to forced swimming test. Two phases of the experiment were conducted. In the acute model, rats were administered ultrapure water (control), fluoxetine, WMO, or the indicated active compound (rosmarinic acid, RA) three times in one day. In the sub-acute model, rats were respectively administered ultrapure water (control), fluoxetine, or three dosages of WMO once a day for 10 days. Locomotor activity and depression-like behavior were examined using the open field test and the forced swimming test, respectively. The levels of relevant neurotransmitters and their metabolites in the frontal cortex, amygdala, hippocampus, and striatum were analyzed by high performance liquid chromatography. In the acute model, WMO and RA significantly reduced depressive-like behavior but the type of related neurotransmitter could not be determined. The results indicated that the effect of WMO administration on the reduction of immobility time was associated with an increase in swimming time of the rats, indicative of serotonergic neurotransmission modulation. Chromatography data validated that the activity of WMO was associated with a reduction in the serotonin turnover rate. The present study shows the serotonergic antidepressant-like activity of WMO. Hence, WMO may offer a serotonergic antidepressant activity to prevent depression and to assist in conventional therapies. Copyright © 2015. Published by Elsevier Ireland Ltd.

Analyzing the experiences of adolescent control rats: Effects of the absence of physical or social stimulation on anxiety-like behaviour are dependent on the test.

PubMed

Joshi, Namrata; Leslie, Ronald A; Perrot, Tara S

2017-10-01

The present study was designed to systematically assess the control experience routinely used in our laboratory as part of studies on predator odour stress. Specifically, we examined effects of the physical and social components of this control experience on measures of anxiety-like behaviour in adolescent rats. Adolescent animals are at increased susceptibility to environmental perturbations and have been used for such studies much less often. Long-Evans rats of both sexes were subjected to physical stimulation (Exposed or Unexposed) and social stimulation (Single-Housed or Pair-Housed), resulting in four groups. Exposed rats received six 30-min exposures to an enclosed arena containing an unscented piece of cat collar occurring between adolescence and early adulthood, while Unexposed remained in the home cage. Groups of Exposed and Unexposed animals were housed singly (Single-Housed) from early adolescence to early adulthood or Pair-Housed during this time. Experimental procedures began in adolescence and involved repeated assessment of startle amplitude (measure of anxiety-like behaviour) and prepulse inhibition (PPI; a measure of sensorimotor gating) to gauge the short-term impact of social and/or physical stimulation. All animals were re-paired in adulthood prior to a final startle/PPI session to assess if isolation limited to adolescence could impose long-term effects that were not reversible. We also measured anxiety-like behaviour in adulthood using an extended open field test (EOFT; addition of novel objects to the open field on later days), and the elevated plus maze task (EPM), as well as a sucrose preference test (SPT) to measure anhedonia. An absence of social or physical stimulation resulted in increased startle amplitude and some measures of anxiety-like behaviour in the EOFT, but a reduction in such anxiety-like behaviour in the EPM task. These results suggest common neural substrates for the physical and social experiences. Performance in the SPT was unaltered by any experimental treatments. Sensorimotor gating, as measured by PPI, was increased in the absence of physical stimulation with no short-term effect of isolation, or of re-pairing. These results indicate the importance of considering individual components of the rearing environment of rats, while showing the need to use multiple assays of anxiety-like behaviour. Copyright © 2017. Published by Elsevier Inc.

Paternal stress prior to conception alters DNA methylation and behaviour of developing rat offspring.

PubMed

Mychasiuk, R; Harker, A; Ilnytskyy, S; Gibb, R

2013-06-25

Although there has been an abundance of research focused on offspring outcomes associated with maternal experiences, there has been limited examination of the relationship between paternal experiences and offspring brain development. As spermatogenesis is a continuous process, experiences that have the ability to alter epigenetic regulation in fathers may actually change developmental trajectories of offspring. The purpose of this study was to examine the effects of paternal stress prior to conception on behaviour and the epigenome of both male and female developing rat offspring. Male Long-Evans rats were stressed for 27 consecutive days and then mated with control female rats. Early behaviour was tested in offspring using the negative geotaxis task and the open field. At P21 offspring were sacrificed and global DNA methylation levels in the hippocampus and frontal cortex were analysed. Paternal stress prior to conception altered behaviour of all offspring on the negative geotaxis task, delaying acquisition of the task. In addition, male offspring demonstrated a reduction in stress reactivity in the open field paradigm spending more time than expected in the centre of the open field. Paternal stress also altered DNA methylation patterns in offspring at P21, global methylation was reduced in the frontal cortex of female offspring, but increased in the hippocampus of both male and female offspring. The results from this study clearly demonstrate that paternal stress during spermatogenesis can influence offspring behaviour and DNA methylation patterns, and these affects occur in a sex-dependent manner. Development takes place in the centre of a complex interaction between maternal, paternal, and environmental influences, which combine to produce the various phenotypes and individual differences that we perceive. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Disparate cocaine-induced locomotion as a predictor of choice behavior in rats trained in a delay-discounting task

PubMed Central

Stanis, Jessica J.; Burns, Randi M.; Sherrill, Luke K.; Gulley, Joshua M.

2008-01-01

Heightened impulsivity and differential sensitivity to a drug's behavioral effects are traits that, individually, have been associated with chronic drug use and dependence. Here, we used an animal model to test whether individual differences in cocaine-induced activity are predictive of impulsive choice behavior. Adult, male Sprague-Dawley rats were given cocaine (10 mg/kg, i.p.) and classified into low or high cocaine responders (LCRs and HCRs, respectively) based on their locomotor response in an open-field arena. Rats were then trained in a delay-discounting task that offers a choice between immediately delivered, but smaller reinforcements, or larger reinforcements that are delivered after a delay. We also examined the effects of amphetamine (AMPH; 0.3-1.0 mg/kg) and the 5-HT1A agonist 8-OH-DPAT (0.3-1.0 mg/kg) on delay discounting. Lastly, all rats were retested in the open-field to determine if phenotypes were stable. We observed baseline differences in choice behavior between the groups, with HCRs behaving more impulsively (i.e., choosing the small reinforcement) compared to LCRs. AMPH decreased choice of the large reinforcement in LCRs, but did not alter choice in HCRs. Impulsive choice was increased in both phenotypes following 8-OH-DPAT, with LCRs exhibiting changes across a wider range of delays. When cocaine-induced open-field behavior was retested, responses in LCRs were similar whereas HCRs showed evidence of tolerance. Our results suggest that differential sensitivity to cocaine-induced locomotion is predictive of impulsivity and the potential neurobiological differences in LCRs and HCRs may provide insight into mechanisms contributing to vulnerability for chronic drug use and/or dependence. PMID:18539407

Effects of methimepip and JNJ-5207852 in Wistar rats exposed to an open-field with and without object and in Balb/c mice exposed to a radial-arm maze.

PubMed

Abuhamdah, Rushdie M A; van Rensburg, Ruan; Lethbridge, Natasha L; Ennaceur, Abdel; Chazot, Paul L

2012-01-01

The role of the histamine H(3) receptor (H(3)R) in anxiety is controversial, due to limitations in drug selectivity and limited validity of behavioral tests used in previous studies. In the present report, we describe two experiments. In the first one, Wistar rats were treated with an H(3)R agonist (methimepip), and exposed to an open-field. In the second one, Balb/c mice were treated with H(3)R agonist (methimepip) or antagonist (JNJ-5207852), and exposed to an open space 3D maze which is a modified version of the radial-arm maze. C57BL/6J saline treated mice were included for comparisons. When exposed to an empty open field, Wistar rats spent more time in the outer area and made very low number of brief crossings in the central area. However, when an object occupied the central area, rats crossed frequently into and spent a long time in the central area. Administration of a range of different doses of methimepip (selective H(3)R agonist) reduced the entries into the central area with a novel object, indicating enhanced avoidance response. In the 3D maze, both Balb/c and C57BL/6J saline-treated mice crossed frequently onto the bridges that radiate from the central platform but only C57BL/6J mice crossed onto the arms which extend the bridges. This suggests that Balb/c mice are more anxious than C57BL/6J mice. Neither methimepip nor JNJ-5207852 (selective H(3)R antagonist/inverse agonist) induced entry into the arms of the maze, indicative of lack of anxiolytic effects.

Interaction of Electromagnetic Fields with Biosynthetic Processes in Connective Tissue Cells

DTIC Science & Technology

1989-12-01

Normal Chondrocytes.............................................10 Swarm Rat Chondrosarcoma Cells..................................15 Conclusions...articular cartilage, and in rat chondrosarcoma cells (a continuous cell line). Another long-term goal is to study the possible role of fields in...Investigators have recently found that bovine [12, 13, 14], rabbit [15], and human [161 chondrocytes as well as Swarm rat chondrosarcoma cells [171 isolated a

Influence of gender and the oestrous cycle on in vitro contractile responses of the rat urinary bladder to cholinergic stimulation

PubMed Central

Longhurst, Penelope A; Levendusky, Mark

2000-01-01

Experiments were done to determine the influence of gender and the oestrous cycle on rat urinary bladder contractility in response to cholinergic stimulation. Bladder strips from female rats responded to high frequency stimulation with smaller contractile responses than did strips from males, and to low concentrations of carbachol with greater responses. The decreased responsiveness of bladder strips from female rats to electrical field stimulation can be primarily attributed to the rats in the oestrous stage of the oestrous cycle. Bladder strips from female rats in all stages of the oestrous cycle were more sensitive to carbachol than those from males, but there were no differences in sensitivity to electrical field stimulation. The contractile responses of strips from both male and female rats to carbachol were antagonized by muscarinic antagonists with the following rank order of affinity (pA2) estimates: 4-DAMP>>pirenzepine>methoctramine, suggesting that the receptor mediating contraction was the M3 subtype. There were no differences in pA2 values between bladder strips from male and female rats. The data indicate that responsiveness of bladder strips to electrical field stimulation and carbachol is altered in female rats in the oestrous stage of the oestrous cycle. Furthermore, gender influences the sensitivity of rat bladder to muscarinic stimulation. PMID:10991909

Intracerebroventricular oxytocin administration in rats enhances object recognition and increases expression of neurotrophins, microtubule-associated protein 2, and synapsin I.

PubMed

Havranek, Tomas; Zatkova, Martina; Lestanova, Zuzana; Bacova, Zuzana; Mravec, Boris; Hodosy, Julius; Strbak, Vladimir; Bakos, Jan

2015-06-01

Brain oxytocin regulates a variety of social and affiliative behaviors and affects also learning and memory. However, mechanisms of its action at the level of neuronal circuits are not fully understood. The present study tests the hypothesis that molecular factors required for memory formation and synaptic plasticity, including brain-derived neurotrophic factor, neural growth factor, nestin, microtubule-associated protein 2 (MAP2), and synapsin I, are enhanced by central administration of oxytocin. We also investigated whether oxytocin enhances object recognition and acts as anxiolytic agent. Therefore, male Wistar rats were infused continuously with oxytocin (20 ng/µl) via an osmotic minipump into the lateral cerebral ventricle for 7 days; controls were infused with vehicle. The object recognition test, open field test, and elevated plus maze test were performed on the sixth, seventh, and eighth days from starting the infusion. No significant effects of oxytocin on anxious-like behavior were observed. The object recognition test showed that oxytocin-treated rats significantly preferred unknown objects. Oxytocin treatment significantly increased gene expression and protein levels of neurotrophins, MAP2, and synapsin I in the hippocampus. No changes were observed in nestin expression. Our results provide the first direct evidence implicating oxytocin as a regulator of brain plasticity at the level of changes of neuronal growth factors, cytoskeletal proteins, and behavior. The data support assumption that oxytocin is important for short-term hippocampus-dependent memory. © 2015 Wiley Periodicals, Inc.

NASA's Desert RATS Science Backroom: Remotely Supporting Planetary Exploration

NASA Technical Reports Server (NTRS)

Cohen, Barbara A.; Eppler, Dean; Gruener, John; Horz, Fred; Ming, Doug; Yingst, R. Aileen

2012-01-01

NASA's Desert Research and Technology Studies (Desert RATS) is a multi-year series of tests designed to exercise planetary surface hardware and operations in conditions where long-distance, multi-day roving is achievable. In recent years, a D-RATS science backroom has conducted science operations and tested specific operational approaches. Approaches from the Apollo, Mars Exploration Rovers and Phoenix missions were merged to become the baseline for these tests. In 2010, six days of lunar-analog traverse operations were conducted during each week of the 2-week test, with three traverse days each week conducted with voice and data communications continuously available, and three traverse days conducted with only two 1-hour communications periods per day. In 2011, a variety of exploration science scenarios that tested operations for a near-earth asteroid using several small exploration vehicles and a single habitat. Communications between the ground and the crew in the field used a 50-second one-way delay, while communications between crewmembers in the exploration vehicles and the habitat were instantaneous. Within these frameworks, the team evaluated integrated science operations management using real-time science operations to oversee daily crew activities, and strategic level evaluations of science data and daily traverse results. Exploration scenarios for Mars may include architectural similarities such as crew in a habitat communicating with crew in a vehicle, but significantly more autonomy will have to be given to the crew rather than step-by-step interaction with a science backroom on Earth.

Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats

PubMed Central

Zhang, Qing; Miller, Christopher; Bible, Jesse; Li, Jiliang; Xu, Xiaoqing; Mehta, Nozer; Gilligan, James; Vignery, Agnès; Scholz, Jodi A Carlson

2012-01-01

Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH). Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture. PMID:24710549

Neuroprotective effect of curcumin on hippocampal injury in 6-OHDA-induced Parkinson's disease rat.

PubMed

Yang, Jiaqing; Song, Shilei; Li, Jian; Liang, Tao

2014-06-01

Clinically, Parkinson's disease (PD)-related neuronal lesions commonly occur. The purpose of this study is to investigate potential therapeutic effect of curcumin against hippocampal damage of 6-hydroxydopamine (6-OHDA)-PD rat model. These results showed that curcumin significantly increased the body weight of 6-OHDA-impaired rats (P<0.01), and reversed the anhedonia in rats induced by 6-OHDA impairment (P<0.01). Meanwhile, behavioral manifestations of curcumin-treated PD rats were effectively ameliorated as shown in open field test (P<0.01). In addition, curcumin increased the contents of monoaminergic neurotransmitters (P<0.01), such as dopamine (DA) and norepinephrine (NE), in hippocampal homogenate through high performance liquid chromatography (HPLC) assay. Curcumin effectively alleviated the 6-OHDA-induced hippocampal damage as observed in hematoxylin-eosin (H&E) staining. Furthermore, curcumin obviously up-regulated hippocampal brain derived neurotrophic factor (BDNF), TrkB, phosphatidylinositide 3-kinases (PI3K) protein expressions, respectively as shown in Western blot analysis. These findings demonstrated that curcumin mediated the neuroprotection against 6-OHDA-induced hippocampus neurons in rats, which the underlying mechanism is involved in activating BDNF/TrkB-dependent pathway for promoting neural regeneration of hippocampal tissue. Copyright © 2014 Elsevier GmbH. All rights reserved.

Analgesic effect of the electromagnetic resonant frequencies derived from the NMR spectrum of morphine.

PubMed

Verginadis, Ioannis I; Simos, Yannis V; Velalopoulou, Anastasia P; Vadalouca, Athina N; Kalfakakou, Vicky P; Karkabounas, Spyridon Ch; Evangelou, Angelos M

2012-12-01

Exposure to various types of electromagnetic fields (EMFs) affects pain specificity (nociception) and pain inhibition (analgesia). Previous study of ours has shown that exposure to the resonant spectra derived from biologically active substances' NMR may induce to live targets the same effects as the substances themselves. The purpose of this study is to investigate the potential analgesic effect of the resonant EMFs derived from the NMR spectrum of morphine. Twenty five Wistar rats were divided into five groups: control group; intraperitoneal administration of morphine 10 mg/kg body wt; exposure of rats to resonant EMFs of morphine; exposure of rats to randomly selected non resonant EMFs; and intraperitoneal administration of naloxone and simultaneous exposure of rats to the resonant EMFs of morphine. Tail Flick and Hot Plate tests were performed for estimation of the latency time. Results showed that rats exposed to NMR spectrum of morphine induced a significant increase in latency time at time points (p < 0.05), while exposure to the non resonant random EMFs exerted no effects. Additionally, naloxone administration inhibited the analgesic effects of the NMR spectrum of morphine. Our results indicate that exposure of rats to the resonant EMFs derived from the NMR spectrum of morphine may exert on animals similar analgesic effects to morphine itself.

Effects of melatonin on aluminium-induced neurobehavioral and neurochemical changes in aging rats.

PubMed

Allagui, M S; Feriani, A; Saoudi, M; Badraoui, R; Bouoni, Z; Nciri, R; Murat, J C; Elfeki, A

2014-08-01

This study aimed to investigate the potential protective effects of melatonin (Mel) against aluminium-induced neurodegenerative changes in aging Wistar rats (24-28months old). Herein, aluminium chloride (AlCl3) (50mg/kg BW/day) was administered by gavage, and melatonin (Mel) was co-administered to a group of Al-treated rats by an intra-peritoneal injection at a daily dose of 10mg/kg BW for four months. The findings revealed that aluminium administration induced a significant decrease in body weight associated with marked mortality for the old group of rats, which was more pronounced in old Al-treated rats. Behavioural alterations were assessed by 'open fields', 'elevated plus maze' and 'Radial 8-arms maze' tests. The results demonstrated that Mel co-administration alleviated neurobehavioral changes in both old and old Al-treated rats. Melatonin was noted to play a good neuroprotective role, reducing lipid peroxidation (TBARs), and enhancing enzymatic (SOD, CAT and GPx) activities in the brain organs of old control and old Al-treated rats. Mel treatment also reversed the decrease of AChE activity in the brain tissues, which was confirmed by histological sections. Overall, the results showed that Mel administration can induce beneficial effects for the treatment of Al-induced neurobehavioral and neurochemical changes in the central nervous system (CNS). Copyright © 2014 Elsevier Ltd. All rights reserved.

Age-dependent change in exploratory behavior of male rats following exposure to threat stimulus: effect of juvenile experience.

PubMed

Arakawa, Hiroyuki

2007-07-01

The ontogeny of exploratory behavior depending on the intensity of threat in a modified open-field was investigated in male rats aged 40, 65, and 130 days, by comparing with less threatening condition with no shock and more threatening condition where they were exposed to mild electric shock. The number of crossings in a dim peripheral alley was counted as the level of activity. The total duration of stay in the central area was measured as the level of exploration. The number of entries and stretch-attend postures into a bright center square were measured as active exploratory behavior and the risk assessment behavior, respectively. When exposed to mild shock prior to the test, 40-day-old rats decreased these exploratory behaviors, while 65- and 130-day-old rats increased active exploratory behavior (Experiment 1). A lower level of exploratory behavior following a mild shock was found in 65 and 130-day-old rats isolated during the juvenile stage, but not in rats isolated after puberty (Experiment 2). These findings suggest that the direction of changes in exploratory behavior of male rats following an increase in potential danger showed ontogenetic transition, which is mediated by social experiences as juveniles, but not as adults. This transition may be associated with the emergence of active exploratory behavior during the juvenile stage, which is activated by social interaction.

Disruption of behavior and brain metabolism in artificially reared rats.

PubMed

Aguirre-Benítez, Elsa L; Porras, Mercedes G; Parra, Leticia; González-Ríos, Jacquelina; Garduño-Torres, Dafne F; Albores-García, Damaris; Avendaño, Arturo; Ávila-Rodríguez, Miguel A; Melo, Angel I; Jiménez-Estrada, Ismael; Mendoza-Garrido, Ma Eugenia; Toriz, César; Diaz, Daniel; Ibarra-Coronado, Elizabeth; Mendoza-Ángeles, Karina; Hernández-Falcón, Jesús

2017-12-01

Early adverse life stress has been associated to behavioral disorders that can manifest as inappropriate or aggressive responses to social challenges. In this study, we analyzed the effects of artificial rearing on the open field and burial behavioral tests and on GFAP, c-Fos immunoreactivity, and glucose metabolism measured in anxiety-related brain areas. Artificial rearing of male rats was performed by supplying artificial milk through a cheek cannula and tactile stimulation, mimicking the mother's licking to rat pups from the fourth postnatal day until weaning. Tactile stimulation was applied twice a day, at morning and at night, by means of a camel brush on the rat anogenital area. As compared to mother reared rats, greater aggressiveness, and boldness, stereotyped behavior (burial conduct) was observed in artificially reared rats which occurred in parallel to a reduction of GFAP immunoreactivity in somatosensory cortex, c-Fos immunoreactivity at the amygdala and primary somatosensory cortex, and lower metabolism in amygdala (as measured by 2-deoxi-2-[ 18 fluoro]-d-glucose uptake, assessed by microPET imaging). These results could suggest that tactile and/or chemical stimuli from the mother and littermates carry relevant information for the proper development of the central nervous system, particularly in brain areas involved with emotions and social relationships of the rat. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1413-1429, 2017. © 2017 Wiley Periodicals, Inc.

Serotonergic activation of locomotor behavior and posture in one-day old rats.

PubMed

Swann, Hillary E; Kempe, R Blaine; Van Orden, Ashley M; Brumley, Michele R

2016-04-01

The purpose of this study was to determine what dose of quipazine, a serotonergic agonist, facilitates air-stepping and induces postural control and patterns of locomotion in newborn rats. Subjects in both experiments were 1-day-old rat pups. In Experiment 1, pups were restrained and tested for air-stepping in a 35-min test session. Immediately following a 5-min baseline, pups were treated with quipazine (1.0, 3.0, or 10.0 mg/kg) or saline (vehicle control), administered intraperitoneally in a 50 μL injection. Bilateral alternating stepping occurred most frequently following treatment with 10.0 mg/kg quipazine, however the percentage of alternating steps, interlimb phase, and step period were very similar between the 3.0 and 10.0 mg/kg doses. For interlimb phase, the forelimbs and hindlimbs maintained a near perfect anti-phase pattern of coordination, with step period averaging about 1s. In Experiment 2, pups were treated with 3.0 or 10.0 mg/kg quipazine or saline, and then were placed on a surface (open field, unrestrained). Both doses of quipazine resulted in developmentally advanced postural control and locomotor patterns, including head elevation, postural stances, pivoting, crawling, and a few instances of quadrupedal walking. The 3.0 mg/kg dose of quipazine was the most effective at evoking sustained locomotion. Between the 2 experiments, behavior exhibited by the rat pup varied based on testing environment, emphasizing the role that environment and sensory cues exert over motor behavior. Overall, quipazine administered at a dose of 3.0 mg/kg was highly effective at promoting alternating limb coordination and inducing locomotor activity in both testing environments. Published by Elsevier B.V.

Changes in Dpysl2 expression are associated with prenatally stressed rat offspring and susceptibility to schizophrenia in humans

PubMed Central

LEE, HWAYOUNG; JOO, JAESOON; NAH, SEONG-SU; KIM, JONG WOO; KIM, HYUNG-KI; KWON, JUN-TACK; LEE, HWA-YOUNG; KIM, YOUNG OCK; KIM, HAK-JAE

2015-01-01

Exposure to stress during critical periods of fetal brain development is an environmental risk factor for the development of schizophrenia in adult offspring. In the present study, a repeated-variable stress paradigm was applied to pregnant rats during the last week of gestation, which is analogous to the second trimester of brain development in humans. Behavioral and proteomic analyses were conducted in prenatally-stressed (PNS) adult offspring and non-stressed (NS) adult controls. In the behavioral tests, grooming behavior in the social interaction test, line-crossing behavior in the open field test, and swimming behavior in the forced swimming test were decreased in the PNS group. Western blot analysis and immunohistochemical analysis revealed that the expression of dihydropyrimidinase-like 2 (Dpysl2) or collapsin response mediator protein 2 (Crmp2) was downregulated in the prefrontal cortex and hippocampus of rats in the PNS group. Subsequently, single-nucleotide polymorphisms (SNPs) of the human dihydropyrimidinase-like 2 (DPYSL2) gene were analyzed in a population. Two functional SNPs (rs9886448 in the promoter region and rs2289593 in the exon region) were associated with susceptibility to schizophrenia. The present findings demonstrated that the downregulation of genes such as Dpysl2 and Dypsl3 in a rat model of prenatal stress may affect subsequent behavioral changes and that polymorphisms of the DPYSL2 gene in humans may be associated with the development of schizophrenia. Taken together with previous studies investigating the association between the DPYSL2 gene and schizophrenia, the present findings may contribute additional evidence regarding developmental theories of the pathophysiology of schizophrenia. PMID:25847191

Evaluation of the effect of acute sibutramine in female rats in the elevated T-maze and elevated plus-maze tests.

PubMed

Santos, Raliny O; de Assunção, Gabriela L M; de Medeiros, Diogo M B; de Sousa Pinto, Icaro A; de Barros, Keizianny S; Soares, Bruno L; André, Eunice; Gavioli, Elaine C; de Paula Soares-Rachetti, Vanessa

2014-02-01

Sibutramine is a serotonin and norepinephrine reuptake inhibitor indicated for the treatment of obesity. A pre-clinical study showed that acute administration of sibutramine promoted anxiolytic- and panicolytic-like effects in male rats. However, in clinical reports, sibutramine favoured the onset of panic attacks in women. In this study, the effect of sibutramine on experimental anxiety in females and the relevance of different oestrous cycle phases for this effect were analysed. In experiment 1, both male and female rats were submitted to acute intraperitoneal injection of sibutramine or vehicle 30 min. before testing in the elevated T-maze (ETM) and in the open-field test (OF). Females in the pro-oestrus (P), oestrus (E), early dioestrus (ED) and late dioestrus (LD) phases were tested in the ETM and OF (experiment 2) or in the elevated plus-maze (EPM) 30 min. after the injection of sibutramine. Sibutramine impaired the escape response in the ETM in both males and females. This effect was observed for P, E and ED, but not for LD females. Sibutramine altered neither the inhibitory avoidance in the ETM nor the behaviour of females in the EPM. Thus, sibutramine promoted a panicolytic-like effect in female rats cycling at P, E and ED, but not in the LD phase and did not alter behaviours related to anxiety in both ETM and EPM. Considering that pre-clinical studies aiming the screening of anxiolytic drugs employ male rodents, data here obtained reinforce the importance of better understanding the effects of drugs in females. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

Influence of multi-walled carbon nanotubes on the cognitive abilities of Wistar rats

PubMed Central

Sayapina, Nina V.; Sergievich, Alexander A.; Kuznetsov, Vladimir L.; Chaika, Vladimir V.; Lisitskaya, Irina G.; Khoroshikh, Pavel P.; Batalova, Tatyana A.; Tsarouhas, Kostas; Spandidos, Demetrios; Tsatsakis, Aristidis M.; Fenga, Concettina; Golokhvast, Kirill S.

2016-01-01

Studies of the neurobehavioral effects of carbon nanomaterials, particularly those of multi-walled carbon nanotubes (MWCNTs), have concentrated on cognitive effects, but data are scarce. The aim of this study was to assess the influence of MWCNTs on a number of higher nervous system functions of Wistar rats. For a period of 10 days, two experimental groups were fed with MWCNTs of different diameters (MWCNT-1 group, 8–10 nm; MWCNT-2 group, 18–20 nm) once a day at a dosage of 500 mg/kg. In the open-field test, reductions of integral indications of researching activity were observed for the two MWCNT-treated groups, with a parallel significant (P<0.01) increase in stress levels for these groups compared with the untreated control group. In the elevated plus-maze test, integral indices of researching activity in the MWCNT-1 and MWCNT-2 groups reduced by day 10 by 51 and 62%, respectively, while rat stress levels remained relatively unchanged. In the universal problem solving box test, reductions in motivation and energy indices of researching activity were observed in the two experimental groups. Searching activity in the MWCNT-1 group by day 3 was reduced by 50% (P<0.01) and in the MWCNT-2 group the relevant reduction reached 11.2%. By day 10, the reduction compared with controls, was 64% (P<0.01) and 58% (P<0.01) for the MWCNT-1 and MWCNT-2 groups, respectively. In conclusion, a series of specific tests demonstrated that MWCNT-treated rats experienced a significant reduction of some of their cognitive abilities, a disturbing and worrying finding, taking into consideration the continuing and accelerating use of carbon nanotubes in medicine and science. PMID:27588053

Slow Physical Growth, Delayed Reflex Ontogeny, and Permanent Behavioral as Well as Cognitive Impairments in Rats Following Intra-generational Protein Malnutrition

PubMed Central

Naik, Aijaz A.; Patro, Ishan K.; Patro, Nisha

2015-01-01

Environmental stressors including protein malnutrition (PMN) during pre-, neo- and post-natal age have been documented to affect cognitive development and cause increased susceptibility to neuropsychiatric disorders. Most studies have addressed either of the three windows and that does not emulate the clinical conditions of intra-uterine growth restriction (IUGR). Such data fail to provide a complete picture of the behavioral alterations in the F1 generation. The present study thus addresses the larger window from gestation to F1 generation, a new model of intra-generational PMN. Naive Sprague Dawley (SD) dams pre-gestationally switched to LP (8% protein) or HP (20% protein) diets for 45 days were bred and maintained throughout gestation on same diets. Pups born (HP/LP dams) were maintained on the respective diets post-weaningly. The present study aimed to show the sex specific differences in the neurobehavioral evolution and behavioral phenotype of the HP/LP F1 generation pups. A battery of neurodevelopmental reflex tests, behavioral (Open field and forelimb gripstrength test), and cognitive [Elevated plus maze (EPM) and Morris water maze (MWM)] assays were performed. A decelerated growth curve with significantly restricted body and brain weight, delays in apparition of neuro-reflexes and poor performance in the LP group rats was recorded. Intra-generational PMN induced poor habituation-with-time in novel environment exploration, low anxiety and hyperactive like profile in open field test in young and adult rats. The study revealed poor forelimb neuromuscular strength in LP F1 pups till adulthood. Group occupancy plots in MWM test revealed hyperactivity with poor learning, impaired memory retention and integration, thus modeling the signs of early onset Alzehemier phenotype. In addition, a gender specific effect of LP diet with severity in males and favoring female sex was also noticed. PMID:26696810

Food Restriction Increases Acquisition, Persistence and Drug Prime-Induced Expression of a Cocaine-Conditioned Place Preference in Rats

PubMed Central

Zheng, Danielle; de Vaca, Soledad Cabeza; Carr, Kenneth D.

2011-01-01

Cocaine conditioned place preference (CPP) is more persistent in food-restricted than ad libitum fed rats. This study assessed whether food restriction acts during conditioning and/or expression to increase persistence. In Experiment 1, rats were food-restricted during conditioning with a 7.0 mg/kg (i.p.) dose of cocaine. After the first CPP test, half of the rats were switched to ad libitum feeding for three weeks, half remained on food restriction, and this was followed by CPP testing. Rats tested under the ad libitum feeding condition displayed extinction by the fifth test. Their CPP did not reinstate in response to overnight food deprivation or a cocaine prime. Rats maintained on food restriction displayed a persistent CPP. In Experiment 2, rats were ad libitum fed during conditioning with the 7.0 mg/kg dose. In the first test only a trend toward CPP was displayed. Rats maintained under the ad libitum feeding condition did not display a CPP during subsequent testing and did not respond to a cocaine prime. Rats tested under food-restriction also did not display a CPP, but expressed a CPP following a cocaine prime. In Experiment 3, rats were ad libitum fed during conditioning with a 12.0 mg/kg dose. After the first test, half of the rats were switched to food restriction for three weeks. Rats that were maintained under the ad libitum condition displayed extinction by the fourth test. Their CPP was not reinstated by a cocaine prime. Rats tested under food-restriction displayed a persistent CPP. These results indicate that food restriction lowers the threshold dose for cocaine CPP and interacts with a previously acquired CPP to increase its persistence. In so far as CPP models Pavlovian conditioning that contributes to addiction, these results suggest the importance of diet and the physiology of energy balance as modulatory factors. PMID:22074687

Food restriction increases acquisition, persistence and drug prime-induced expression of a cocaine-conditioned place preference in rats.

PubMed

Zheng, Danielle; Cabeza de Vaca, Soledad; Carr, Kenneth D

2012-01-01

Cocaine conditioned place preference (CPP) is more persistent in food-restricted than ad libitum fed rats. This study assessed whether food restriction acts during conditioning and/or expression to increase persistence. In Experiment 1, rats were food-restricted during conditioning with a 7.0 mg/kg (i.p.) dose of cocaine. After the first CPP test, half of the rats were switched to ad libitum feeding for three weeks, half remained on food restriction, and this was followed by CPP testing. Rats tested under the ad libitum feeding condition displayed extinction by the fifth test. Their CPP did not reinstate in response to overnight food deprivation or a cocaine prime. Rats maintained on food restriction displayed a persistent CPP. In Experiment 2, rats were ad libitum fed during conditioning with the 7.0 mg/kg dose. In the first test only a trend toward CPP was displayed. Rats maintained under the ad libitum feeding condition did not display a CPP during subsequent testing and did not respond to a cocaine prime. Rats tested under food-restriction also did not display a CPP, but expressed a CPP following a cocaine prime. In Experiment 3, rats were ad libitum fed during conditioning with a 12.0 mg/kg dose. After the first test, half of the rats were switched to food restriction for three weeks. Rats that were maintained under the ad libitum condition displayed extinction by the fourth test. Their CPP was not reinstated by a cocaine prime. Rats tested under food-restriction displayed a persistent CPP. These results indicate that food restriction lowers the threshold dose for cocaine CPP and interacts with a previously acquired CPP to increase its persistence. In so far as CPP models Pavlovian conditioning that contributes to addiction, these results suggest the importance of diet and the physiology of energy balance as modulatory factors. Copyright © 2011 Elsevier Inc. All rights reserved.

Long-term trihexyphenidyl exposure alters neuroimmune response and inflammation in aging rat: relevance to age and Alzheimer's disease.

PubMed

Huang, Yuqi; Zhao, Zhe; Wei, Xiaoli; Zheng, Yong; Yu, Jianqiang; Zheng, Jianquan; Wang, Liyun

2016-07-01

Clinical studies have shown an association between long-term anticholinergic (AC) drug exposure and Alzheimer's disease (AD) pathogenesis, which has been primarily investigated in Parkinson's disease (PD). However, long-term AC exposure as a risk factor for developing neurodegenerative disorders and the exact mechanisms and potential for disease progression remain unclear. Here, we have addressed the issue using trihexyphenidyl (THP), a commonly used AC drug in PD patients, to determine if THP can accelerate AD-like neurodegenerative progression and study potential mechanisms involved. Male Sprague-Dawley rats (SD) were intraperitoneally injected with THP (0.3 and 1.0 mg/kg) or normal saline (NS) for 7 months. Alterations in cognitive and behavioral performance were assessed using the Morris water maze (MWM) and open field tests. After behavior tests, whole genome oligo microarrays, quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry, and immunofluorescence-confocal were used to investigate the global mechanisms underlying THP-induced neuropathology with aging. Compared with NS controls, the MWM test results showed that THP-treated rats exhibited significantly extended mean latencies during the initial 3 months of testing; however, this behavioral deficit was restored between the fourth and sixth month of MWM testing. The same tendencies were confirmed by MWM probe and open field tests. Gene microarray analysis identified 68 (47 %) upregulated and 176 (53 %) downregulated genes in the "THP-aging" vs. "NS-aging" group. The most significant populations of genes downregulated by THP were the immune response-, antigen processing and presentation-, and major histocompatibility complex (MHC)-related genes, as validated by qRT-PCR. The decreased expression of MHC class I in THP-treated aging brains was confirmed by confocal analysis. Notably, long-term THP treatment primed hippocampal and cortical microglia to undergo an inflammatory phenotypic switch, causing microgliosis and microglia activation, which were positively accompanied by pathological misfolded tau lesions. Our findings suggest that immune response and neuroinflammation represent a pivotal mechanism in THP-induced AD-like neuropathology processes with long-term exposure to AC drugs.

Effect of Hypericum perforatum on different models of movement disorders in rats.

PubMed

Reis, Elizete M; Röpke, Jivago; Busanello, Alcindo; Reckziegel, Patrícia; Leal, Caroline Q; Wagner, Caroline; Boligon, Aline A; Athayde, Margareth L; Fachinetto, Roselei

2013-10-01

The effects of Hypericum perforatum, a plant with antidepressant action, were evaluated in models of abnormal movements in rats, brought about by administration of fluphenazine or reserpine. The number of vacuous chewing movements (VCMs) and locomotor activity (the number of crossings and rears in the open field test) were measured. In experiment 1, rats received a single administration of fluphenazine enanthate (25 mg/kg, intramuscular) and/or daily treatment with H. perforatum (300 mg/kg, in place of drinking water) for 7 days. Fluphenazine increased VCMs and decreased locomotor activity. H. perforatum had no effect on either the number of VCMs or the locomotor activity. In experiment 2, rats received reserpine every 2 days for 6 days (0.5 mg/kg, subcutaneous) and/or H. perforatum (300 mg/kg, in place of drinking water) daily for 16 days beginning 10 days before the first administration of reserpine. Reserpine treatment increased VCMs and decreased locomotor activity. H. perforatum had no effect on either the number of VCMs or the number of rears but did prevent the effect of reserpine on the number of crossings. In conclusion, H. perforatum failed to protect against orofacial movements induced by fluphenazine or reserpine in rats.

Resveratrol ameliorates chronic unpredictable mild stress-induced depression-like behavior: involvement of the HPA axis, inflammatory markers, BDNF, and Wnt/β-catenin pathway in rats.

PubMed

Yang, Xin-Hua; Song, Su-Qi; Xu, Yun

2017-01-01

Classic antidepressant drugs are modestly effective across the population and most are associated with intolerable side effects. Recently, numerous lines of evidence suggest that resveratrol (RES), a natural polyphenol, possesses beneficial therapeutic activity for depression. The aim of the present study was to explore whether RES exhibits an antidepressant-like effect in a depression model and to explore the possible mechanism. A depression model was established via chronic unpredictable mild stress (CUMS), after which the model rats in the RES and fluoxetine groups received a daily injection of RES or fluoxetine, respectively. The sucrose preference test, open field test, and forced swimming test were used to explore the antidepressant-like effects of RES. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the plasma corticosterone concentration and hypothalamic mRNA expression of corticotrophin-releasing hormone. The plasma interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) concentrations were measured by enzyme-linked immunosorbent assay. Hippocampal protein expression of brain-derived neurotrophic factor (BDNF) and the Wnt/β-catenin pathway were analyzed by western blot. The results showed that RES relieved depression-like behavior of CUMS rats, as indicated by the increased sucrose preference and the decreased immobile time. Rats that received RES treatment exhibited reduced plasma corticosterone levels and corticotrophin-releasing hormone mRNA expression in the hypothalamus, suggesting that the hyperactivity of the HPA axis in CUMS rats was reversed by RES. Moreover, after RES treatment, the rats exhibited increased plasma IL-6, CRP, and TNF-α concentrations. Furthermore, RES treatment upregulated the hippocampal protein levels of BDNF and the relative ratio of p-β-catenin/β-catenin while downregulating the relative ratio of p-GSK-3β/GSK-3β. Our findings suggest that RES improved depressive behavior in CUMS rats by downregulating HPA axis hyperactivity, increasing BDNF expression and plasma IL-6, CRP, and TNF-α concentrations, and regulating the hippocampal Wnt/β-catenin pathway.

Rearing in an enriched environment attenuated hyperactivity and inattention in the Spontaneously Hypertensive Rats, an animal model of Attention-Deficit Hyperactivity Disorder.

PubMed

Botanas, Chrislean Jun; Lee, Hyelim; de la Peña, June Bryan; Dela Peña, Irene Joy; Woo, Taeseon; Kim, Hee Jin; Han, Doug Hyun; Kim, Bung-Nyun; Cheong, Jae Hoon

2016-03-01

Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, characterized by symptoms of hyperactivity, inattention, and impulsivity. It is commonly treated with psychostimulants that typically begins during childhood and lasts for an extended period of time. However, there are concerns regarding the consequences of chronic psychostimulant treatment; thus, there is a growing search for an alternative management for ADHD. One non-pharmacological management that is gaining much interest is environmental enrichment. Here, we investigated the effects of rearing in an enriched environment (EE) on the expression of ADHD-like symptoms in the Spontaneously Hypertensive Rats (SHRs), an animal model of ADHD. SHRs were reared in EE or standard environment (SE) from post-natal day (PND) 21 until PND 49. Thereafter, behavioral tests that measure hyperactivity (open field test [OFT]), inattention (Y-maze task), and impulsivity (delay discounting task) were conducted. Additionally, electroencephalography (EEG) was employed to assess the effects of EE on rat's brain activity. Wistar-Kyoto (WKY) rats, the normotensive counterpart of the SHRs, were used to determine whether the effects of EE were specific to a particular genetic background. EE improved the performance of the SHRs and WKY rats in the OFT and Y-maze task, but not the delay discounting task. Interestingly, EE induced significant EEG changes in WKY rats, but not in the SHRs. These findings show that rearing environment may play a role in the expression of ADHD-like symptoms in the SHRs and that EE may be considered as a putative complementary approach in managing ADHD symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

Tannoid principles of Emblica officinalis renovate cognitive deficits and attenuate amyloid pathologies against aluminum chloride induced rat model of Alzheimer's disease.

PubMed

Justin Thenmozhi, Arokiasamy; Dhivyabharathi, Mathiyazahan; William Raja, Tharsius Raja; Manivasagam, Thamilarasan; Essa, Musthafa Mohamed

2016-07-01

Emblica officinalis is mentioned as a maharasayana in many Ayurvedic texts and promotes intelligence, memory, freedom from disease, longevity, and strength of the senses. The present study has been designed to explore the memory-enhancing effect of the tannoid principles of E. officinalis (EoT) at the biochemical, anatomical, behavioral, and molecular levels against aluminum chloride (AlCl3) induced Alzheimer's disease (AD) in rats. Aluminum is reported to have an important role in the etiology, pathogenesis, and development of AD. Male Wistar rats were divided into control, AlCl3 treated, AlCl3 and EoT (50, 100, and 200 mg/kg bw) co-treated, and EoT (200 mg/kg bw) alone treated groups. In control and experimental rats, behavior tests including water maze and open field test, estimation of aluminum, assay of acetylcholinesterase (AChE) activity, and expression of amyloidogenic proteins were performed. Intraperitonial injection of AlCl3 (100 mg/kg bw) for 60 days significantly elevated the concentration of aluminum (Al), activity of AChE and protein expressions of amyloid precursor protein, A-beta1-42, beta-, and gamma-secretases as compared to control group in hippocampus and cortex. Co-administration of EoT orally to AlCl3 rats for 60 days significantly revert back the Al concentration, AChE activity, and A-beta synthesis-related molecules in the studied brain regions. The spatial learning, memory, and locomotor impairments observed in AlCl3 treated rats were significantly attenuated by EoT. Therefore, EoT may be a promising therapy in ameliorating neurotoxicity of aluminum, however further studies are warranted to elucidate the exact mechanism of action of EoT.

Postnatal LPS Challenge Impacts Escape Learning and Expression of Plasticity Factors Mmp9 and Timp1 in Rats: Effects of Repeated Training.

PubMed

Trofimov, Alexander; Strekalova, Tatyana; Mortimer, Niall; Zubareva, Olga; Schwarz, Alexander; Svirin, Evgeniy; Umriukhin, Aleksei; Svistunov, Andrei; Lesch, Klaus-Peter; Klimenko, Victor

2017-08-01

Bacterial intoxication associated with inflammatory conditions during development can impair brain functions, in particular evolutionarily novel forms of memory, such as explicit learning. Little is known about the dangers of early-life inflammation on more basic forms of learning, for example, the acquisition of motor escape abilities, which are generally better preserved under pathological conditions. To address this limitation in knowledge, an inflammatory response was elicited in Wistar pups by lipopolysaccharide (LPS) injections (25 μg/kg) on postnatal days P15, P18 and P21. The acquisition of escape behaviour was tested from P77 by active avoidance footshock model and water maze. Open-field behaviour and blood corticosterone levels were also measured. Rat brain tissue was collected from pups 2 h post-injection and from adult rats which either underwent escape training on P77-P81 or remained untrained. mRNA levels of developmental brain plasticity factors MMP-9 and TIMP-1 were investigated in the medial prefrontal cortex and ventral/dorsal hippocampus. LPS-challenged rats displayed moderately deficient escape responses in both memory tests, increased freezing behaviour and, surprisingly, reduced blood cortisol levels. Mmp9 and Timp1, and their ratio to one another, were differentially altered in pups versus adult untrained rats but remained unchanged overall in rats trained in either learning task. Together, our data indicate that systemic pro-inflammatory response during early postnatal development has long-lasting effects, including on the acquisition of motor escape abilities and plasticity factor expression, into adulthood. Our data suggest that altered stress response could possibly mediate these deviations and repeated training might generate positive effects on plasticity under the employed conditions.

Treatment with lacosamide impedes generalized seizures in a rodent model of cortical dysplasia.

PubMed

Nemes, Ashley D; O'Dwyer, Rebecca; Najm, Imad M; Ying, Zhong; Gonzalez-Martinez, Jorge; Alexopoulos, Andreas V

2017-10-01

Epilepsy is a common neurologic disorder resulting in spontaneous, recurrent seizures. About 30-40% of patients are not responsive to pharmacologic therapies. This may be due to the differences between individual patients such as etiology, underlying pathophysiology, and seizure focus, and it highlights the importance of new drug discovery and testing in this field. Our goal was to determine the efficacy of lacosamide (LCM), a drug approved for the treatment of focal seizures, in a model of generalized epilepsy with cortical dysplasia (CD). We sought to compare LCM to levetiracetam (LEV), a drug that is currently used for the treatment of both partial and generalized epilepsy and to test its proficiency. Pregnant rats were irradiated to produce pups with malformed cortices in a model of CD, which will be referred to as the "first hit." Adult animals, developed normally (NL) and irradiated (XRT), were surgically implanted with electroencephalography (EEG) electrodes. Baseline EEG was recorded on all rats prior to pretreatments with either LCM, LEV, or placebo (PBO). After 30 min, all rats were injected with a subconvulsive dose of pentylenetetrazole (PTZ), a γ-aminobutyric acid receptor A (GABA A ) antagonist used to provoke generalized seizures as a "second hit." LCM and LEV were both effective against seizures induced by PTZ. XRT rats had a higher seizure incidence with longer and more severe seizures than NL rats. Seizure duration was decreased with both LCM and LEV in all animals. In XRT rats, there was a significant reduction in acute seizure incidence and severity with both LCM and LEV after PTZ injection. Our results suggest that LCM could be used as a potential treatment option for generalized epilepsy with CD as the underlying pathology. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Ropren® treatment reverses anxiety-like behavior and monoamines levels in gonadectomized rat model of Alzheimer's disease.

PubMed

Fedotova, Julia; Soultanov, Vagif; Nikitina, Tamara; Roschin, Victor; Ordyan, Natalia; Hritcu, Lucian

2016-10-01

Previous studies indicated that reduced androgen levels may contribute to both physical and cognitive disorders in men, including Alzheimer's disease. New drug candidates for Alzheimer's disease in patients with androgen deficiency should ideally be able to act not only on multiple brain targets but also to correct impaired endocrine functions in hypogonadal men with Alzheimer's disease. Ropren ® is one such candidate for the treatment of Alzheimer's disease in men with an imbalance of androgens. Accordingly, the aim of the current study was to examine the effects of long-term Ropren ® administration (8.6mg/kg, orally, once daily, for 28 days) on the anxiety-like behavior and monoamines levels in the rat hippocampus using a β-amyloid (25-35) rat model of Alzheimer's disease following gonadectomy. Ropren ® was administered to the gonadectomized (GDX) rats and GDX rats treated with testosterone propionate (TP, 0.5mg/kg, subcutaneous, once daily, for 28 days). Anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light-dark test (LDT), locomotor and grooming activities were assessed in the open field test (OFT). Ropren ® alone or in combination with TP-induced anxiolytic effects as evidenced in the EPM and in the LDT and increased locomotor activity in the OFT. Additionally, it was observed that dopamine (DA) and serotonin (5-HT) levels increased while 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio in the hippocampus decreased. Our results indicate that Ropren ® has a marked anxiolytic-like action due to an increase in the monoamines levels in the experimental rat model of Alzheimer's disease with altered levels of androgens. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Electrical stimulation of the lateral habenula produces enduring inhibitory effect on cocaine seeking behavior.

PubMed

Friedman, Alexander; Lax, Elad; Dikshtein, Yahav; Abraham, Lital; Flaumenhaft, Yakov; Sudai, Einav; Ben-Tzion, Moshe; Ami-Ad, Lavi; Yaka, Rami; Yadid, Gal

2010-11-01

The lateral habenula (LHb) is critical for modulation of negative reinforcement, punishment and aversive responses. In light of the success of deep-brain-stimulation (DBS) in the treatment of neurological disorders, we explored the use of LHb DBS as a method of intervention in cocaine self-administration, extinction, and reinstatement in rats. An electrode was implanted into the LHb and rats were trained to self-administer cocaine (21 days; 0.25-1 mg/kg) until they achieved at least three days of stable performance (as measured by daily recordings of active lever presses in self-administration cages). Thereafter, rats received DBS in the presence or absence of cocaine. DBS reduced cocaine seeking behavior during both self-administration and extinction training. DBS also attenuated the rats' lever presses following cocaine reinstatement (5-20 mg/kg) in comparison to sham-operated rats. These results were also controlled by the assessment of physical performance as measured by water self-administration and an open field test, and by evaluation of depressive-like manifestations as measured by the swim and two-bottles-choice tests. In contrast, LHb lesioned rats demonstrated increased cocaine seeking behavior as demonstrated by a delayed extinction response. In the ventral tegmental area, cocaine self-administration elevated glutamatergic receptor subunits NR1 and GluR1 and scaffolding protein PSD95, but not GABA(A)β, protein levels. Following DBS treatment, levels of these subunits returned to control values. We postulate that the effect of both LHb modulation and LHb DBS on cocaine reinforcement may be via attenuation of the cocaine-induced increase in glutaminergic input to the VTA. Copyright © 2010 Elsevier Ltd. All rights reserved.

Electrical stimulation of the lateral habenula produces enduring inhibitory effect on cocaine seeking behavior

PubMed Central

Friedman, Alexander; Lax, Elad; Dikshtein, Yahav; Abraham, Lital; Flaumenhaft, Yakov; Sudai, Einav; Ben-Tzion, Moshe; Ami-Ad, Lavi; Yaka, Rami; Yadid, Gal

2010-01-01

The lateral habenula (LHb) is critical for modulation of negative reinforcement, punishment and aversive responses. In light of the success of deep-brain-stimulation (DBS) in the treatment of neurological disorders, we explored the use of LHb DBS as a method of intervention in cocaine self-administration, extinction, and reinstatement in rats. An electrode was implanted into the LHb and rats were trained to self-administer cocaine (21 days; 0.25–1 mg/kg) until they achieved at least three days of stable performance (as measured by daily recordings of active lever presses in self-administration cages). Thereafter, rats received DBS in the presence or absence of cocaine. DBS reduced cocaine seeking behavior during both self-administration and extinction training. DBS also attenuated the rats' lever presses following cocaine reinstatement (5–20 mg/kg) in comparison to sham-operated rats. These results were also controlled by the assessment of physical performance as measured by water self-administration and an open field test, and by evaluation of depressive-like manifestations as measured by the swim and two-bottles-choice tests. In contrast, LHb lesioned rats demonstrated increased cocaine seeking behavior as demonstrated by a delayed extinction response. In the ventral tegmental area, cocaine self-administration elevated glutamatergic receptor subunits NR1 and GluR1 and scaffolding protein PSD95, but not GABAAβ, protein levels. Following DBS treatment, levels of these subunits returned to control values. We postulate that the effect of both LHb modulation and LHb DBS on cocaine reinforcement may be via attenuation of the cocaine-induced increase in glutaminergic input to the VTA. PMID:20600170

Volumetric changes in the aging rat brain and its impact on cognitive and locomotor functions.

PubMed

Hamezah, Hamizah Shahirah; Durani, Lina Wati; Ibrahim, Nor Faeizah; Yanagisawa, Daijiro; Kato, Tomoko; Shiino, Akihiko; Tanaka, Sachiko; Damanhuri, Hanafi Ahmad; Ngah, Wan Zurinah Wan; Tooyama, Ikuo

2017-12-01

Impairments in cognitive and locomotor functions usually occur with advanced age, as do changes in brain volume. This study was conducted to assess changes in brain volume, cognitive and locomotor functions, and oxidative stress levels in middle- to late-aged rats. Forty-four male Sprague-Dawley rats were divided into four groups: 14, 18, 23, and 27months of age. 1 H magnetic resonance imaging (MRI) was performed using a 7.0-Tesla MR scanner system. The volumes of the lateral ventricles, medial prefrontal cortex (mPFC), hippocampus, striatum, cerebellum, and whole brain were measured. Open field, object recognition, and Morris water maze tests were conducted to assess cognitive and locomotor functions. Blood was taken for measurements of malondialdehyde (MDA), protein carbonyl content, and antioxidant enzyme activity. The lateral ventricle volumes were larger, whereas the mPFC, hippocampus, and striatum volumes were smaller in 27-month-old rats than in 14-month-old rats. In behavioral tasks, the 27-month-old rats showed less exploratory activity and poorer spatial learning and memory than did the 14-month-old rats. Biochemical measurements likewise showed increased MDA and lower glutathione peroxidase (GPx) activity in the 27-month-old rats. In conclusion, age-related increases in oxidative stress, impairment in cognitive and locomotor functions, and changes in brain volume were observed, with the most marked impairments observed in later age. Copyright © 2017. Published by Elsevier Inc.

Adolescent social isolation affects schizophrenia-like behavior and astrocyte biomarkers in the PFC of adult rats.

PubMed

Sun, Lan; Min, Li; Zhou, Hao; Li, Man; Shao, Feng; Wang, Weiwen

2017-08-30

Social isolation is regarded as a cause of schizophrenia spectrum disorders. Animal models of schizophrenia are constructed by repeated early environment deprivation as an important paradigm to reveal its pathological mechanism. Male Sprague Dawley rats were assigned to either social-rearing (SR) or isolated-rearing (IR) groups during postnatal days (PNDs) 21-34. On PND 56, all rats underwent behavioral testing including locomotor activity, anxiety-related behaviors in an open field and prepulse inhibition (PPI). Then, the rats were sacrificed and prefrontal cortex (PFC) tissues were separated for high-throughput proteomics analysis and Western blot validation. Rats of the IR group showed increased spontaneous locomotion, increased anxiety-like behavior and disrupted PPI compared with rats of the SR group. Based on proteomics analysis, a total of 124 PFC proteins were found to be significantly differentially expressed between the SR group and the IR group, the most remarkable of which were glial fibrillary acidic protein (GFAP), Annexin A2 (ANXA2) and vimentin (VIM), three astrocyte biomarkers. Further Western blot measurement confirmed that the levels of GFAP, ANXA2 and VIM were increased significantly in IR rats. Adolescent social isolation induced schizophrenia-like behaviors and significantly different expression of 124 PFC proteins in adult rats, especially GFAP, ANXA2 and VIM, which suggests that astrocyte development might be involved in the neural mechanism of schizophrenia. Copyright © 2017. Published by Elsevier B.V.

Metyrapone Reveals That Previous Chronic Stress Differentially Impairs Hippocampal-dependent Memory

PubMed Central

CONRAD, CHERYL D.; MAULDIN-JOURDAIN, MELISSA L.; HOBBS, REBECCA J.

2007-01-01

Chronic stress facilitates fear conditioning in rats with hippocampal neuronal atrophy and in rats in which the atrophy is prevented with tianeptine, a serotonin re-uptake enhancer. The purpose of this study was to determine whether the lack of dissociation between fear conditioning performance and hippocampal integrity was masked by the presence of endogenous corticosteroids during training. As in previous studies, rats were stressed by daily restraint (6 h/day for 21 days), trained in the conditioning chamber (day 23), and then assessed for conditioned fear (day 25) at a time when hippocampal dendritic atrophy persists. On the training day, half of the control and stressed rats were injected with metyrapone to reduce corticosterone release. Two hours later, two paired or unpaired presentations of tone and footshock were delivered. Although metyrapone reduced conditioned fear in all rats, only stressed rats showed dissociated fear conditioning (i.e. tone conditioning was reduced while contextual conditioning was eliminated). Chronically stressed rats, regardless of metyrapone treatment displayed more rearing in the open field when tested immediately after the completion of fear conditioning. These data support the hypothesis that increased emotionality and enhanced fear conditioning exhibited by chronically stressed rats may be due to endogenous corticosterone secretion at the time of fear conditioned training. Moreover, these data suggest that chronic stress impairs hippocampal-dependent processes more robustly than hippocampal-independent processes after metyrapone to reduce corticosterone secretion during aversive training. PMID:18301732

Social Effects on Rat Spatial Choice in an Open Field Task

ERIC Educational Resources Information Center

Keller, Matthew R.; Brown, Michael F.

2011-01-01

Pairs of rats foraged in trials either together or separately in an open field apparatus for pellets hidden in discreet locations in a 5 x 5 matrix. Trial duration was either 1 or 4 min. The tendency to choose locations that had earlier been visited by another rat was examined by comparing the choices made in the presence and absence of the other…

[Effect of genotype and day or night time of testing on mice behavior in the light-dark box and the open-field tests].

PubMed

Morozova, M V; Kulikov, A V

2010-01-01

The light-dark box (LDB) and the open-field (OF) tests are widespread experimental models for studying locomotion and anxiety in laboratory rats and mice. The fact that rodents are nocturnal animals and more active at night raises a critical question of whether behavioral experiments carried out in the light phase are methodologically correct. Parameters of behavior of four mouse strains (C57BL/6J, DBA2/J, AKR/J and CBA/LacJ) in the light-dark box and open-field tests in the light and dark phases were compared. No significant influence of the phase of testing on anxiety in LDB and OF tests was revealed. In the OF test CBA mice showed increased locomotor activity, whereas AKR and C57BL/6 mice showed increased defecation in the dark phase. It was concluded that: 1) the phase of testing is not crucial for the expression of anxiety in LDB and OF; 2) the sensitivity to the phase of testing depends on the genotype; 3) the indices of behavior in the genotypes sensitive to the phase of testing (locomotion in the CBA and defecation in the AKR and C57BL/6 mouse strains) are increased in the dark phase.

[The influence of application of a low-frequency magnetic field on the serum corticosterone level (an experimental study)].

PubMed

Alabovskiĭ, V V; Gotovskiĭ, M Iu; Vinokurov, A A; Maslov, O V

2013-01-01

The results of analysis of the literature publications suggest the necessity of experimental studies aimed at investigation of modulating effect of low-frequency magnetic fields on endocrine organs. The present study was carried out using 200 outbred white male rats (body weight 200-220 g). Corticosterone was measured in blood sera following the application of a low-frequency magnetic field (20 and 53 Hz with induction from 0.4 to 6 mT) generated by a Mini-Expert-T apparatus for induction magnetic therapy during 30 minutes. It was shown that the application of the alternating magnetic field to the adrenal region of the rats in the selected frequency and induction ranges caused a significant increase in the serum corticosterone levels. The results of the present study on the hormonal activity of rat adrenals give reason to consider the influence of the alternating magnetic fields as being modulatory. Analysis of the data thus obtained has demonstrated the non-linear dependence of glucocorticoid activity of the rat adrenal glands on the induction strength of the alternating magnetic field.

Repeated exposures to chlorpyrifos lead to spatial memory retrieval impairment and motor activity alteration.

PubMed

Yan, Changhui; Jiao, Lifei; Zhao, Jun; Yang, Haiying; Peng, Shuangqing

2012-07-01

Chlorpyrifos (CPF) is one of the most commonly used insecticides throughout the world and has become one of the major pesticides detected in farm products. Chronic exposures to CPF, especially at the dosages without eliciting any systemic toxicity, require greater attention. The purpose of this study was, therefore, to evaluate the behavioral effects of repeated low doses (doses that do not produce overt signs of cholinergic toxicity) of CPF in adult rats. Male rats were given 0, 1.0, 5.0 or 10.0mg/kg of CPF through intragastric administration daily for 4 consecutive weeks. The behavioral functions were assessed in a series of behavioral tests, including water maze task, open-field test, grip strength and rotarod test. Furthermore, the present study was designed to evaluate the effects of repeated exposures to CPF on water maze recall and not acquisition. The results showed that the selected doses only had mild inhibition effects on cholinesterase activity, and have no effects on weight gain and daily food consumption. Performances in the spatial retention task (Morris water maze) were impaired after the 4-week exposure to CPF, but the performances of grip strength and rotarod test were not affected. Motor activities in the open field were changed, especially the time spent in the central zone increased. The results indicated that repeated exposures to low doses of CPF may lead to spatial recall impairments, behavioral abnormalities. However, the underlying mechanism needs further investigations. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of an Individual Readiness Assurance Test on a Team Readiness Assurance Test in the Team-Based Learning of Physiology

ERIC Educational Resources Information Center

Gopalan, Chaya; Fox, Dainielle J.; Gaebelein, Claude J.

2013-01-01

We examined whether requiring an individual readiness assurance test (iRAT) before a team readiness assurance test (tRAT) would benefit students in becoming better problem solvers in physiology. It was tested in the form of tRAT scores, the time required to complete the tRAT assignment, and individual performance on the unit examinations. Students…

Marked rapid alterations in nocturnal pineal serotonin metabolism in mice and rats exposed to weak intermittent magnetic fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lerchl, A.; Nonaka, K.O.; Stokkan, K.A.

Adult AMES mice and male Sprague Dawley rats were exposed to an artificial magnetic field, generated by Helmholtz coils. 3.5 hours after the onset of darkness the coils were activated for one hour resulting in an inversion of the horizontal component of the earth's magnetic field. The coils were activated and deactivated at 5 min intervals during the 1 hour exposure period. In both mice and rats, the levels of serotonin in the pineal were markedly increased by the exposure. In rats, an increase of pineal 5-hydroxyindole acetic acid and a decrease of the activity of the pineal enzyme serotonin-N-acetyltransferasemore » also was observed. However, pineal and serum melatonin levels were not altered. The results indicate that the metabolism of serotonin in the pineal is quickly affected by the exposure of animals to a magnetic field.« less

Nociceptive neuronal Fc-gamma receptor I is involved in IgG immune complex induced pain in the rat.

PubMed

Jiang, Haowu; Shen, Xinhua; Chen, Zhiyong; Liu, Fan; Wang, Tao; Xie, Yikuan; Ma, Chao

2017-05-01

Antigen-specific immune diseases such as rheumatoid arthritis are often accompanied by pain and hyperalgesia. Our previous studies have demonstrated that Fc-gamma-receptor type I (FcγRI) is expressed in a subpopulation of rat dorsal root ganglion (DRG) neurons and can be directly activated by IgG immune complex (IgG-IC). In this study we investigated whether neuronal FcγRI contributes to antigen-specific pain in the naïve and rheumatoid arthritis model rats. In vitro calcium imaging and whole-cell patch clamp recordings in dissociated DRG neurons revealed that only the small-, but not medium- or large-sized DRG neurons responded to IgG-IC. Accordingly, in vivo electrophysiological recordings showed that intradermal injection of IgG-IC into the peripheral receptive field could sensitize only the C- (but not A-) type sensory neurons and evoke action potential discharges. Pain-related behavioral tests showed that intradermal injection of IgG-IC dose-dependently produced mechanical and thermal hyperalgesia in the hindpaw of rats. These behavioral effects could be alleviated by localized administration of non-specific IgG or an FcγRI antibody, but not by mast cell stabilizer or histamine antagonist. In a rat model of antigen-induced arthritis (AIA) produced by methylated bovine serum albumin, FcγRI were found upregulated exclusively in the small-sized DRG neurons. In vitro calcium imaging revealed that significantly more small-sized DRG neurons responded to IgG-IC in the AIA rats, although there was no significant difference between the AIA and control rats in the magnitude of calcium changes in the DRG neurons. Moreover, in vivo electrophysiological recordings showed that C-nociceptive neurons in the AIA rats exhibited a greater incidence of action potential discharges and stronger responses to mechanical stimuli after IgG-IC was injected to the receptive fields. These results suggest that FcγRI expressed in the peripheral nociceptors might be directly activated by IgG-IC and contribute to antigen-specific pain in pathological conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of primary and recurrent sacral chordoma on the motor and nociceptive function of hindlimbs in rats: an orthotopic spine model.

PubMed

Sarabia-Estrada, Rachel; Ruiz-Valls, Alejandro; Shah, Sagar R; Ahmed, A Karim; Ordonez, Alvaro A; Rodriguez, Fausto J; Guerrero-Cazares, Hugo; Jimenez-Estrada, Ismael; Velarde, Esteban; Tyler, Betty; Li, Yuxin; Phillips, Neil A; Goodwin, C Rory; Petteys, Rory J; Jain, Sanjay K; Gallia, Gary L; Gokaslan, Ziya L; Quinones-Hinojosa, Alfredo; Sciubba, Daniel M

2017-08-01

OBJECTIVE Chordoma is a slow-growing, locally aggressive cancer that is minimally responsive to conventional chemotherapy and radiotherapy and has high local recurrence rates after resection. Currently, there are no rodent models of spinal chordoma. In the present study, the authors sought to develop and characterize an orthotopic model of human chordoma in an immunocompromised rat. METHODS Thirty-four immunocompromised rats were randomly allocated to 4 study groups; 22 of the 34 rats were engrafted in the lumbar spine with human chordoma. The groups were as follows: UCH1 tumor-engrafted (n = 11), JHC7 tumor-engrafted (n = 11), sham surgery (n = 6), and intact control (n = 6) rats. Neurological impairment of rats due to tumor growth was evaluated using open field and locomotion gait analysis; pain response was evaluated using mechanical or thermal paw stimulation. Cone beam CT (CBCT), MRI, and nanoScan PET/CT were performed to evaluate bony changes due to tumor growth. On Day 550, rats were killed and spines were processed for H & E-based histological examination and immunohistochemistry for brachyury, S100β, and cytokeratin. RESULTS The spine tumors displayed typical chordoma morphology, that is, physaliferous cells filled with vacuolated cytoplasm of mucoid matrix. Brachyury immunoreactivity was confirmed by immunostaining, in which samples from tumor-engrafted rats showed a strong nuclear signal. Sclerotic lesions in the vertebral body of rats in the UCH1 and JHC7 groups were observed on CBCT. Tumor growth was confirmed using contrast-enhanced MRI. In UCH1 rats, large tumors were observed growing from the vertebral body. JHC7 chordoma-engrafted rats showed smaller tumors confined to the bone periphery compared with UCH1 chordoma-engrafted rats. Locomotion analysis showed a disruption in the normal gait pattern, with an increase in the step length and duration of the gait in tumor-engrafted rats. The distance traveled and the speed of rats in the open field test was significantly reduced in the UCH1 and JHC7 tumor-engrafted rats compared with controls. Nociceptive response to a mechanical stimulus showed a significant (p < 0.001) increase in the paw withdrawal threshold (mechanical hypalgesia). In contrast, the paw withdrawal response to a thermal stimulus decreased significantly (p < 0.05) in tumor-engrafted rats. CONCLUSIONS The authors developed an orthotopic human chordoma model in rats. Rats were followed for 550 days using imaging techniques, including MRI, CBCT, and nanoScan PET/CT, to evaluate lesion progression and bony integrity. Nociceptive evaluations and locomotion analysis were performed during follow-up. This model reproduces cardinal signs, such as locomotor and sensory deficits, similar to those observed clinically in human patients. To the authors' knowledge, this is the first spine rodent model of human chordoma. Its use and further study will be essential for pathophysiology research and the development of new therapeutic strategies.

Effects of exposure to 2100MHz GSM-like radiofrequency electromagnetic field on auditory system of rats.

PubMed

Çeliker, Metin; Özgür, Abdulkadir; Tümkaya, Levent; Terzi, Suat; Yılmaz, Mustafa; Kalkan, Yıldıray; Erdoğan, Ender

The use of mobile phones has become widespread in recent years. Although beneficial from the communication viewpoint, the electromagnetic fields generated by mobile phones may cause unwanted biological changes in the human body. In this study, we aimed to evaluate the effects of 2100MHz Global System for Mobile communication (GSM-like) electromagnetic field, generated by an electromagnetic fields generator, on the auditory system of rats by using electrophysiological, histopathologic and immunohistochemical methods. Fourteen adult Wistar albino rats were included in the study. The rats were divided randomly into two groups of seven rats each. The study group was exposed continuously for 30days to a 2100MHz electromagnetic fields with a signal level (power) of 5.4dBm (3.47mW) to simulate the talk mode on a mobile phone. The control group was not exposed to the aforementioned electromagnetic fields. After 30days, the Auditory Brainstem Responses of both groups were recorded and the rats were sacrificed. The cochlear nuclei were evaluated by histopathologic and immunohistochemical methods. The Auditory Brainstem Responses records of the two groups did not differ significantly. The histopathologic analysis showed increased degeneration signs in the study group (p=0.007). In addition, immunohistochemical analysis revealed increased apoptotic index in the study group compared to that in the control group (p=0.002). The results support that long-term exposure to a GSM-like 2100MHz electromagnetic fields causes an increase in neuronal degeneration and apoptosis in the auditory system. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Cannabis exacerbates depressive symptoms in rat model induced by reserpine.

PubMed

Khadrawy, Yasser A; Sawie, Hussein G; Abdel-Salam, Omar M E; Hosny, Eman N

2017-05-01

Cannabis sativa is one of the most widely recreational drugs and its use is more prevalent among depressed patients. Some studies reported that Cannabis has antidepressant effects while others showed increased depressive symptoms in Cannabis users. Therefore, the present study aims to investigate the effect of Cannabis extract on the depressive-like rats. Twenty four rats were divided into: control, rat model of depression induced by reserpine and depressive-like rats treated with Cannabis sativa extract (10mg/kg expressed as Δ9-tetrahydrocannabinol). The depressive-like rats showed a severe decrease in motor activity as assessed by open field test (OFT). This was accompanied by a decrease in monoamine levels and a significant increase in acetylcholinesterase activity in the cortex and hippocampus. Na + ,K + -ATPase activity increased in the cortex and decreased in the hippocampus of rat model. In addition, a state of oxidative stress was evident in the two brain regions. This was indicated from the significant increase in the levels of lipid peroxidation and nitric oxide. No signs of improvement were observed in the behavioral and neurochemical analyses in the depressive-like rats treated with Cannabis extract. Furthermore, Cannabis extract exacerbated the lipid peroxidation in the cortex and hippocampus. According to the present findings, it could be concluded that Cannabis sativa aggravates the motor deficits and neurochemical changes induced in the cortex and hippocampus of rat model of depression. Therefore, the obtained results could explain the reported increase in the depressive symptoms and memory impairment among Cannabis users. Copyright © 2017 Elsevier B.V. All rights reserved.

GeoLab's First Field Trials, 2010 Desert RATS: Evaluating Tools for Early Sample Characterization

NASA Technical Reports Server (NTRS)

Evans, Cindy A.; Bell, M. S.; Calaway, M. J.; Graff, Trevor; Young, Kelsey

2011-01-01

As part of an accelerated prototyping project to support science operations tests for future exploration missions, we designed and built a geological laboratory, GeoLab, that was integrated into NASA's first generation Habitat Demonstration Unit-1/Pressurized Excursion Module (HDU1-PEM). GeoLab includes a pressurized glovebox for transferring and handling samples collected on geological traverses, and a suite of instruments for collecting preliminary data to help characterize those samples. The GeoLab and the HDU1-PEM were tested for the first time as part of the 2010 Desert Research and Technology Studies (DRATS), NASA's analog field exercise for testing mission technologies. The HDU1- PEM and GeoLab participated in two weeks of joint operations in northern Arizona with two crewed rovers and the DRATS science team.

Chronic ethanol exposure during adolescence in rats induces motor impairments and cerebral cortex damage associated with oxidative stress.

PubMed

Teixeira, Francisco Bruno; Santana, Luana Nazaré da Silva; Bezerra, Fernando Romualdo; De Carvalho, Sabrina; Fontes-Júnior, Enéas Andrade; Prediger, Rui Daniel; Crespo-López, Maria Elena; Maia, Cristiane Socorro Ferraz; Lima, Rafael Rodrigues

2014-01-01

Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage to complete 90 days of age. The open field, inclined plane and the rotarod tests were used to assess the spontaneous locomotor activity and motor coordination performance in adult animals. Following completion of behavioral tests, half of animals were submitted to immunohistochemical evaluation of NeuN (marker of neuronal bodies), GFAP (a marker of astrocytes) and Iba1 (microglia marker) in the cerebral cortex while the other half of the animals were subjected to analysis of oxidative stress markers by biochemical assays. Chronic ethanol intoxication in rats from adolescence to adulthood induced significant motor deficits including impaired spontaneous locomotion, coordination and muscle strength. These behavioral impairments were accompanied by marked changes in all cellular populations evaluated as well as increased levels of nitrite and lipid peroxidation in the cerebral cortex. These findings indicate that continuous ethanol intoxication from adolescence to adulthood is able to provide neurobehavioral and neurodegenerative damage to cerebral cortex.

Activation of AMPA receptor in the infralimbic cortex facilitates extinction and attenuates the heroin-seeking behavior in rats.

PubMed

Chen, Weisheng; Wang, Yiqi; Sun, Anna; Zhou, Linyi; Xu, Wenjin; Zhu, Huaqiang; Zhuang, Dingding; Lai, Miaojun; Zhang, Fuqiang; Zhou, Wenhua; Liu, Huifen

2016-01-26

Infralimbic cortex (IL) is proposed to suppress cocaine seeking after extinction, but whether the IL regulates the extinction and reinstatement of heroin-seeking behavior is unknown. To address this issue, the male SD rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 days, then the rats underwent 7 daily 2h extinction session in the operant chamber. The activation of IL by microinjection PEPA, an allosteric AMPA receptor potentiator into IL before each of extinction session facilitated the extinction responding after heroin self-administration, but did not alter the locomotor activity in an open field testing environment. Other rats were first trained under a FR1 schedule for heroin self-administration for 14 days, followed by 14 days of extinction training, and reinstatement of heroin-seeking induced by cues was measured for 2h. Intra-IL microinjecting of PEPA at 15min prior to test inhibited the reinstatement of heroin-seeking induced by cues. Moreover, the expression of GluR1 in the IL and NAc remarkably increased after treatment with PEPA during the reinstatement. These finding suggested that activation of glutamatergic projection from IL to NAc shell may be involved in the extinction and reinstatement of heroin-seeking. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chronic choline supplementation improves cognitive and motor performance via modulating oxidative and neurochemical status in rats.

PubMed

Tabassum, Saiqa; Haider, Saida; Ahmad, Saara; Madiha, Syeda; Parveen, Tahira

2017-08-01

Choline, an essential nutrient, accounts for multiple functions in the body and brain. While its beneficial effects on healthy adults are not clear, choline supplementation is important during pregnancy for brain development, in elderly patients for support of cognitive performance and in patients with neurological disorders to reduce memory deficits. Thus, the aim of this study is to investigate whether choline administration in healthy adult rats beneficially impacts cognitive and locomotor performance, and associated oxidative and neurochemical outcomes. Two groups, control and choline, received tap water and choline bitartrate, respectively at the dose equivalent to adequate intake for five weeks. Food intake and body weight were monitored daily. Behavioral analysis comprising assessment of cognitive performance (by novel object recognition, passive avoidance and Morris Water Maze test) and locomotor performance (by Open field, Kondziela's inverted screen and beam walking test) were performed. Following testing, rats were decapitated and brain samples were collected for estimation of acetylcholine, redox profile and monoamine measurements. The results showed that chronic choline administration significantly improves cognitive and locomotor performance accompanied by a reduction in oxidative stress, enhanced cholinergic neurotransmission and monoamine levels in the brain of healthy adult rats. Hence, chronic choline intake was found to improve behavioral, oxidative and neurochemical outcomes in the normal population, so it can be suggested that choline tablets can be used as a safe and effective supplement for improving the neurological health of normal individuals and that they might also be beneficial in preventing cognitive and motor disorders later in life. Copyright © 2017 Elsevier Inc. All rights reserved.

Magnetic-field-induced DNA strand breaks in brain cells of the rat.

PubMed Central

Lai, Henry; Singh, Narendra P

2004-01-01

In previous research, we found that rats acutely (2 hr) exposed to a 60-Hz sinusoidal magnetic field at intensities of 0.1-0.5 millitesla (mT) showed increases in DNA single- and double-strand breaks in their brain cells. Further research showed that these effects could be blocked by pretreating the rats with the free radical scavengers melatonin and N-tert-butyl-alpha-phenylnitrone, suggesting the involvement of free radicals. In the present study, effects of magnetic field exposure on brain cell DNA in the rat were further investigated. Exposure to a 60-Hz magnetic field at 0.01 mT for 24 hr caused a significant increase in DNA single- and double-strand breaks. Prolonging the exposure to 48 hr caused a larger increase. This indicates that the effect is cumulative. In addition, treatment with Trolox (a vitamin E analog) or 7-nitroindazole (a nitric oxide synthase inhibitor) blocked magnetic-field-induced DNA strand breaks. These data further support a role of free radicals on the effects of magnetic fields. Treatment with the iron chelator deferiprone also blocked the effects of magnetic fields on brain cell DNA, suggesting the involvement of iron. Acute magnetic field exposure increased apoptosis and necrosis of brain cells in the rat. We hypothesize that exposure to a 60-Hz magnetic field initiates an iron-mediated process (e.g., the Fenton reaction) that increases free radical formation in brain cells, leading to DNA strand breaks and cell death. This hypothesis could have an important implication for the possible health effects associated with exposure to extremely low-frequency magnetic fields in the public and occupational environments. PMID:15121512

40 CFR 799.4360 - Tributyl phosphate.

Code of Federal Regulations, 2011 CFR

2011-07-01

... provisions also apply: (i) Animal selection. Testing shall be performed in laboratory rats. (ii) Duration of... apply: (i) Animal selection. Testing shall be performed in laboratory rats. (ii) Duration of testing...) Animal selection. Testing shall be performed in laboratory rats. (ii) Duration of testing. Animals shall...

Male rats with the testicular feminization mutation of the androgen receptor display elevated anxiety-related behavior and corticosterone response to mild stress

PubMed Central

Zuloaga, Damian G.; Poort, Jessica E.; Jordan, Cynthia L.; Breedlove, S. Marc

2011-01-01

Testosterone influences the hypothalamic-pituitary-adrenal axis, anxiety-related behavior, and sensorimotor gating in rodents, but little is known about the role of the androgen receptor (AR) in mediating these influences. We compared levels of the stress hormone corticosterone at baseline and following exposure to a novel object in an open field in wild type (wt) male and female rats, and male rats with the testicular feminization mutation (Tfm) of the AR, which disables its function. Basal corticosterone was equivalent in all groups, but exposure to a novel object in an open field elicited a greater increase in corticosterone in Tfm males and wt females than in wt males. Tfm males also showed increased behavioral indices of anxiety compared to wt males and females in the test. Analysis of the immediate early gene c-Fos expression after exposure to a novel object revealed greater activation in Tfm males than wt males in some regions (medial preoptic area) and lesser activation in others (dentate gyrus, posterodorsal medial amygdala). No differences were found in a measure of sensorimotor gating (prepulse inhibition of the acoustic startle response), although Tfm males had an increased acoustic startle response compared to wt males and females. These findings demonstrate that ARs play a role in regulating anxiety-related behaviors, as well as corticosterone responses and neural activation following exposure to a mild stressor in rats. PMID:21801726

NON-INVASIVE RADIOFREQUENCY ABLATION OF CANCER TARGETED BY GOLD NANOPARTICLES

PubMed Central

Cardinal, Jon; Klune, John Robert; Chory, Eamon; Jeyabalan, Geetha; Kanzius, John S.; Nalesnik, Michael; Geller, David A.

2008-01-01

Introduction Current radiofrequency ablation (RFA) techniques require invasive needle placement and are limited by accuracy of targeting. The purpose of this study was to test a novel non-invasive radiowave machine that uses RF energy to thermally destroy tissue. Gold nanoparticles were designed and produced to facilitate tissue heating by the radiowaves. Methods A solid state radiowave machine consisting of a power generator and transmitting/receiving couplers which transmit radiowaves at 13.56 MHz was used. Gold nanoparticles were produced by citrate reduction and exposed to the RF field either in solutions testing or after incubation with HepG2 cells. A rat hepatoma model using JM-1 cells and Fisher rats was employed using direct injection of nanoparticles into the tumor to focus the radiowaves for select heating. Temperatures were measured using a fiber-optic thermometer for real-time data. Results Solutions containing gold nanoparticles heated in a time- and power-dependent manner. HepG2 liver cancer cells cultured in the presence of gold nanoparticles achieved adequate heating to cause cell death upon exposure to the RF field with no cytotoxicity attributable to the gold nanoparticles themselves. In vivo rat exposures at 35W using gold nanoparticles for tissue injection resulted in significant temperature increases and thermal injury at subcutaneous injection sites as compared to vehicle (water) injected controls. Discussion These data show that non-invasive radiowave thermal ablation of cancer cells is feasible when facilitated by gold nanoparticles. Future studies will focus on tumor selective targeting of nanoparticles for in vivo tumor destruction. PMID:18656617

Interaction of Electromagnetic Fields with Chondrocytes in Gel Culture

DTIC Science & Technology

1990-02-01

biosynthesis due to applied electromagnetic fields. The results suggest that both normal chondrocytes and swarm rat chondrosarcoma cells in agarose Culture...and Swarm rat chondrosarcoma cells in agarose iii culture can, under proper culture conditions, continue to synthesize ma- trix macromolecules at a...cartilagc, and in rat chondrosarcoma cells (a continuous cell line). The overt gene expression of chondrocytes results in the synthesis and deposition of a

[The regulation of FSH release by the testis. Studies on inhibin].

PubMed

Krause, W

1977-05-12

The FSH release from the hypophysis is suggested to be particularly regulated by a testicular hormone called inhibin. Origin, structure and target organs of inhibin are unknown. Experiments to test some hypotheses in this field are described. Adult male rats, prenatally treated with busulfan, show only Sertoli cells in the semiferous tubules. Experimental cryptorchidism and orchidectomy, however, leads to an increase in FSH levels as observed in normal animals. This indicates the role of Sertoli cells in FSH regulation. Ligation of efferent ducts of testes leads to an increase of FSH levels, too, indicating that an FSH-inhibiting principle cannot be absorbed. Interstitial testis fluid (ITF) of normal rats was applicated to immature female rats. Their FSH release is inhibited, visible in the lower ovarian weight gain following additional hCG-administration. Orchidectomized animals react with a decrease of FSH levels to the application of ITF. Therefore ITF seems to contain a FSH-inhibiting factor. Androgen binding protein-content of epididymes, however, is increased after repeated injections of ITF. It is concluded that testis (probably the Sertoli cells) produces a FSH-inhibiting factor, but ITF contains only small amounts of inhibin.

Rats avoid exposure to HVdc electric fields: a dose response study.

PubMed

Creim, J A; Lovely, R H; Weigel, R J; Forsythe, W C; Anderson, L E

1993-01-01

Rats, given the choice, avoid exposure to alternating current (ac) 60-Hz electric fields at intensities > or = 75 kV/m. This study investigated the generality of this behavior by studying the response of rats when exposed to high voltage direct current (HVdc) electric fields. Three hundred eighty male Long Evans rats were studied in 9 experiments with 40 rats per experiment and in one experiment with 20 rats to determine 1) if rats avoid exposure to HVdc electric fields of varying field strengths, and 2) if avoidance did occur, what role, if any, the concentration of air ions would have on the avoidance behavior. In all experiments a three-compartment glass shuttlebox was used; either the left or right compartment could be exposed to a combination of HVdc electric fields and air ions while the other compartment remained sham-exposed. The third, center compartment was a transition zone between exposure and sham-exposure. In each experiment, the rats were individually assessed in 1-h sessions where half of the rats (n = 20) had the choice to locomote between the two sides being exposed or sham-exposed, while the other half of the rats (n = 20) were sham-exposed regardless of their location, except in one experiment where there was no sham-exposed group. The exposure levels for the first six experiments were 80, 55, 42.5, 30, -36, and -55 kV/m, respectively. The air ion concentration was constant at 1.4 x 10(6) ions/cc for the four positive exposure levels and -1.4 x 10(6) ions/cc for the two negative exposure levels. Rats having a choice between exposure and non-exposure relative to always sham-exposed control animals significantly reduced the amount of time spent on the exposed side at 80 kV/m (P < .002) as they did at both 55 and -55 kV/m (P < .005). No significant differences between groups were observed at 42.5, 30, or -36 kV/m. To determine what role the air ion concentration might have had on the avoidance behavior at field strengths of 55 kV/m or greater, four additional experiments were conducted. The HVdc exposure level was held constant at either -55 kV/m (for three experiments) or -55 kV/m (for 1 experiment) while the air ion concentration was varied between experiments at 2.5 x 10(5) ions/cc, 1.0 x 10(4) for two of the experiments and was below the measurement limit (< +/- 2 x 10(3) ions/cc) for the other two experiments at 55 and -55 kV/m.(ABSTRACT TRUNCATED AT 400 WORDS)

Electroacupuncture Improves Cognitive Function and Hippocampal Neurogenesis after Brain Irradiation.

PubMed

Fan, Xing-Wen; Liu, Huan-Huan; Wang, Hong-Bing; Chen, Fu; Yang, Yu; Chen, Yan; Guan, Shi-Kuo; Wu, Kai-Liang

2017-06-01

Cognitive impairments after brain irradiation seriously affect quality of life for patients, and there is currently no effective treatment. In this study using an irradiated rat model, the role of electroacupuncture was investigated for treatment of radiation-induced brain injury. Animals received 10 Gy exposure to the entire brain, and electroacupuncture was administered 3 days before irradiation as well as up to 2 weeks postirradiation. Behavioral tests were performed one month postirradiation, and rats were then sacrificed for histology or molecular studies. Electroacupuncture markedly improved animal performance in the novel place recognition test. In the emotion test, electroacupuncture reduced defecation during the open-field test, and latency to consumption of food in the novelty suppressed feeding test. Brain irradiation inhibited the generation of immature neurons, but did not cause neural stem cell loss. Electroacupuncture partially restored hippocampal neurogenesis. Electroacupuncture decreased the amount of activated microglia and increased resting microglia in the hippocampus after irradiation. In addition, electroacupuncture promoted mRNA and protein expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. In conclusion, electroacupuncture could improve cognitive function and hippocampal neurogenesis after irradiation, and the protective effect of electroacupuncture was associated with the modulation of microglia and upregulation of BDNF in the hippocampus.