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Sample records for rat forced swimming

  1. Structure of the rat behaviour in the forced swimming test.

    PubMed

    Lino-de-Oliveira, Cilene; De Lima, Thereza C M; de Pádua Carobrez, Antonio

    2005-03-30

    Forced swimming test (FST) or 'behavioural despair' test is a useful screening for antidepressant drugs. The FST predictability has been improved by a number of procedural modifications. Description of the behavioural microstructure in FST may help to delineate innovative protocols. Thus, counts of all behaviours emitted during FST in rats (four-month-old Wistar male, n = 63) were recorded and examined by Markovian sequential analysis (MSA) and principal components analysis (PCA). In a second experiment, rats (n = 28) were tested in an open field test (OFT) followed a week later by FST; behaviours in both tests were recorded and analysed by two correlation methods (Pearson's test and sliding window correlation). The descriptive ethological analysis displayed counts of swimming and immobility increased over the course of the test, whereas climbing behaviour decreased. The MSA revealed the occurrence of immobility was predicted by swimming, climbing, and diving behaviours whereas the immobility predicted the occurrence of swimming behaviour and headshakes. The PCA showed duration of immobility and climbing loaded into one component and duration of immobility and swimming loaded into another one. Low as well high levels of climbing behaviour were positively correlated with motor activity in the OFT. In brief, the present data suggest there are at least two different factors that grouped variables related to the behavioural despair in the FST. In addition, altered motor activity could be predicted by the frequency of climbing behaviour recorded in the FST.

  2. Influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats.

    PubMed

    Kitamura, Yoshihisa; Araki, Hiroaki; Nagatani, Tadashi; Takao, Katsuyuki; Shibata, Kazuhiko; Gomita, Yutaka

    2004-12-01

    We studied the influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats. Both single and chronic administration of imipramine potently shortened immobility in naive rats during forced-swim testing. However, chronic, 14-day forced-swim stress testing blocked the immobility-decreasing effect induced by a single administration of imipramine. When imipramine was administered for 14 days concurrently with forced-swim stress testing, immobility was shortened significantly. From the viewpoint of imipramine's effect, these findings suggest that chronic forced-swim stress testing in rats may be an effective animal model for depression.

  3. Role of amygdala MAPK activation on immobility behavior of forced swim rats.

    PubMed

    Huang, Tung-Yi; Lin, Chih-Hung

    2006-10-01

    The role of amygdala mitogen-activated protein kinase (MAPK) in rats during a forced swim test was investigated. The variation of amygdala MAPK level was studied in control rats and early-life maternally deprived rats. A forced swim test was carried out to estimate the immobility level. The data showed that the immobility time of rats that received maternal deprivation in early life was longer than that of control rats and Western blot analysis also showed that the amygdala phospho-MAPK level in maternally deprived rats was almost two times higher than in control rats. Intra-amygdala infusion of PD098059 or U0126, MEK inhibitors, suppressed immobility behavior during the forced swim test in both rats. Western blot analysis also showed that the amygdala MAPK activities in both rats infused with MEK inhibitors were also suppressed in parallel with expression of immobility behavior. The suppressed MAPK activities as well as the restoration of immobility time returned to the original level 48 h later. These results suggest that amygdala MAPK activation might play a role in the regulation of immobility behavior in rats during the forced swim test. Moreover, it could provide a hint that amygdala MAPK activation might be involved in the formation of depression-like behavior.

  4. Reduction in the level of immobilization in forced swim test and ethanol intake in rats by oxygen therapy.

    PubMed

    Kampov-Polevoy, A B; Dubtchenko, V V; Crosby, R D; Halikas, J A

    1993-01-01

    Experiments replicated the previous finding that rats with high immobilization time in the forced swim test (passive rats) consumed more 15% ethanol solution in a free choice situation with tap water than rats with active behavior (active rats). Exposure of passive rats to oxygen under normal and elevated (2 ata) pressure resulted in the decrease in immobilization scores in the forced swim test as well as reduction in alcohol consumption and preference.

  5. Right-but not left-paw use in female rats provides advantage in forced swim tests.

    PubMed

    Soyman, Efe; Tunckol, Elcin; Lacin, Emre; Canbeyli, Resit

    2015-10-15

    Left- and right-pawed adult female Wistar rats were subjected to forced swimming on two consecutive days. Compared to the right-pawed group, left- pawed rats displayed significantly increased immobility from the first to the second swim test and remained significantly more immobile in the second swim test. Both groups performed similarly in spatial learning in the Morris water maze suggesting that left- pawed rats are differentially and specifically susceptible to depressogenic treatment.

  6. Omega-3 fatty acids have antidepressant activity in forced swimming test in Wistar rats.

    PubMed

    Lakhwani, Lalit; Tongia, Sudheer K; Pal, Veerendra S; Agrawal, Rajendra P; Nyati, Prem; Phadnis, Pradeep

    2007-01-01

    Forced swimming test is used to induce a characteristic behavior of immobility in rats, which resembles depression in humans to some extent. We evaluated the effect of omega-3 fatty acids alone as well as compared it with the standard antidepressant therapy with fluoxetine in both acute and chronic studies. In both the studies, rats were divided into 4 groups and subjected to the following drug interventions - Group 1- control: Group 2- fluoxetine in dose of 10 mg/kg subcutaneously 23.5, 5 and 1 h before the test: Group 3- omega-3 fatty acids in dose of 500 mg/kg orally; Group 4- fluoxetine plus omega-3 fatty acids both. In acute study, omega-3 fatty acids were given in single dose 2 h prior to the test while in chronic study omega-3 fatty acids were given daily for a period of 28 days. All animals were subjected to a 15-min pretest followed 24 h later by a 5-min test. A time sampling method was used to score the behavioral activity in each group. The results revealed that in acute study, omega-3 fatty acids do not have any significant effect in forced swimming test. However, in chronic study, omega-3 fatty acids affect the immobility and swimming behavior significantly when compared with control (p < 0.01) without any significant effect on climbing behavior and the efficacy of combination of omega-3 fatty acids and fluoxetine is significantly more than that of fluoxetine alone in changing the behavioral activity of rats in forced swimming test. It leads to the conclusion that omega-3 fatty acids have antidepressant activity per se, and the combination of fluoxetine and omega-3 fatty acids has more antidepressant efficacy than fluoxetine alone in forced swimming test in Wistar rats.

  7. Effect of citalopram in the modified forced swim test in rats.

    PubMed

    Kuśmider, Maciej; Solich, Joanna; Pałach, Paulina; Dziedzicka-Wasylewska, Marta

    2007-01-01

    The present study examined the effect of citalopram (7.5 and 15 mg/kg) in the modified forced swim test (FST) in Wistar rats, in comparison to the effect of desipramine at the same doses. The citalopram at both doses increased swimming behavior, at the cost of climbing and immobility. The administration of desipramine increased climbing behavior while immobility counts were decreased. The modified FST is indeed more sensitive than the conventional FST in describing precisely the behavioral effects of antidepressant drugs, allowing to roughly estimate the contribution of individual neurotransmitter system to the mechanism of action of the studied drug.

  8. Antidepressant-like actions of pregnancy, and progesterone in Wistar rats forced to swim.

    PubMed

    Molina-Hernández, M; Téllez-Alcántara, N P

    2001-07-01

    In rats, some behavioral changes occurring during pregnancy related to the presence of progesterone may be analyzed in the forced swimming task (FST), which is designed to test the antidepressant profile of drugs. The present study was aimed to analyze in pregnant rats, in rats after delivery, or in rats after receiving progesterone those behavioral changes displayed in the FST. We hypothesize that pregnancy and progesterone will produce antidepressant-like effects in rats forced to swim. Therefore, pregnant rats (14th, 17th, and 20th days), or rats after delivery (3rd, and 7th days) were tested in the FST. Ovariectomized rats receiving saline (0.9%; i.p.), clomipramine (1.25 mg/kg; i.p.), or desipramine (2.14 mg/kg; i.p.) for 28 days were also tested in the FST. In a second series of experiments, ovariectomized rats receiving vehicle or progesterone (0.5 mg/kg; or 2.0 mg/kg; sc.) were tested in the FST. Locomotion was evaluated in the open field test. Results showed that in the FST: 1) pregnancy (P < 0.05), or progesterone (P < 0.05), or desipramine (P < 0.05), reduced immobility by increasing climbing; 2) clomipramine (P < 0.05) reduced immobility by increasing swimming; 3) rats tested after delivery displayed similar behavior than control rats. A lower locomotion was observed only at the end of pregnancy. In conclusion, results suggest that during pregnancy, a reproductive process characterized by its high levels of progesterone, antidepressant-like effects can be found.

  9. Urine from stressed rats increases immobility in receptor rats forced to swim: role of 2-heptanone.

    PubMed

    Gutiérrez-García, Ana G; Contreras, Carlos M; Mendoza-López, M Remedios; García-Barradas, Oscar; Cruz-Sánchez, J Samuel

    2007-05-16

    The present study was aimed to determine whether the urine from donor rats, which were physically stressed (UD-PS) by unavoidable electric footshocks, produces despair in receptor partner rats (RP) in the long-term. For each trial, an RP rat was placed during 10 min once per day for 21 days in a small non-movement-restricting cage impregnated with the urine collected from a UD-PS rat. Control rats, free of stimulation, maintained their locomotion and immobility scores at basal values throughout the 21-day test. After 21 days of stressing experience [F(2,90)=15.22, P<0.0001] locomotion significantly increased in RP rats (r=0.938, P<0.01), whereas in the UD-PS group locomotion decreased (r=-0.606, P<0.05). The RP and UD-PS groups displayed the longest time of immobility [F(2,90)=8.83, P<0.001] in the forced-swim test (RP, r=0.886, P<0.05; UD-PS, r=0.962, P<0.001) compared with the control group (r=-0.307, NS). We conclude that the RP became similarly despaired as the UD-PS group through the action of 2-heptanone, a ketonic compound identified in UD-PS urine by HS-GC/MS techniques. This ketone was found to be increased [F(2,15)=3.50, P<0.05] from the 1st day of unavoidable electric footshocks, and to induce despair, an effect reverted [F(2,21)=16.5, P<0.0001] by imipramine (5.0 mg/kg) in another group of rats.

  10. Frequency of climbing behavior as a predictor of altered motor activity in rat forced swimming test.

    PubMed

    Vieira, Cíntia; De Lima, Thereza C M; Carobrez, Antonio de Pádua; Lino-de-Oliveira, Cilene

    2008-11-14

    Previous work has shown that the frequency of climbing behavior in rats submitted to the forced swimming test (FST) correlated to the section's crosses in the open field test, which suggest it might be taken as a predictor of motor activity in rat FST. To investigate this proposal, the frequency, duration, as well as the ratio duration/frequency for each behavior expressed in the FST (immobility, swimming and climbing) were compared in animals treated with a motor stimulant, caffeine (CAF), and the antidepressant, clomipramine (CLM). Male Wistar rats were submitted to 15min of forced swimming (pre-test) and 24h later received saline (SAL, 1ml/kg, i.p.) or CAF (6.5mg/kg, i.p.) 30min prior a 5-min session (test) of FST. To validate experimental procedures, an additional group of rats received three injections of SAL (1ml/kg, i.p.) or clomipramine (CLM, 10mg/kg, i.p.) between the pre-test and test sessions. The results of the present study showed that both drugs, CLM and CAF, significantly reduced the duration of immobility and significantly increased the duration of swimming. In addition, CAF significantly decreased the ratio of immobility, and CLM significantly increased the ratio of swimming and climbing. Moreover, CLM significantly increased the duration of climbing but only CAF increased the frequency of climbing. Thus, it seems that the frequency of climbing could be a predictor of altered motor activity scored directly in the FST. Further, we believe that this parameter could be useful for fast and reliable discrimination between antidepressant drugs and stimulants of motor activity.

  11. Using the rat forced swim test to assess antidepressant-like activity in rodents.

    PubMed

    Slattery, David A; Cryan, John F

    2012-05-03

    The forced swim test (FST) is one of the most commonly used animal models for assessing antidepressant-like behavior. This protocol details using the FST in rats, which takes place over 48 h and is followed by the video analysis of the behavior. The swim test involves the scoring of active (swimming and climbing) or passive (immobility) behavior when rodents are forced to swim in a cylinder from which there is no escape. There are two versions that are used, namely the traditional and modified FSTs, which differ in their experimental setup. For both versions, a pretest of 15 min (although a number of laboratories have used a 10-min pretest with success) is included, as this accentuates the different behaviors in the 5-min swim test following drug treatment. Reduction in passive behavior is interpreted as an antidepressant-like effect of the manipulation, provided it does not increase general locomotor activity, which could provide a false positive result in the FST.

  12. Onion peel water extracts enhance immune status in forced swimming rat model.

    PubMed

    Lee, Hyun-A; Han, Sang-Jun; Hong, Sunhwa; Kim, Dong-Woo; Oh, Gi-Wook; Kim, Okjin

    2014-12-01

    Onion peel contains a high concentration of quercetin and other flavonoids. In this study, the potential immune-enhancing effects of an onion peel water extract (OPE) supplement were investigated by the rat forced swimming test. OPE was prepared using hot water. Thirty-six male Sprague Dawley rats were fed a pellet diet for 1 week and were then randomly divided into six groups: normal control (NC), forced swimming control (FSC), positive control (quercetin 20 mg/kg), and three groups administered 4, 20, or 100 mg/kg of OPE. Oral drug administration was conducted daily for 4 weeks. All rats, except those of NC group, were forced to swim in water and were considered exhausted when they failed to rise to the water surface to breathe within a 7-s period. Blood lymphocyte counts, immune organ weights, histopathological analysis, and serum interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-12 levels were determined. OPE-treated rats consumed more food and had an increased thymic cortex to medulla ratio than that observed in FSC group rats (P<0.05). The area of the white pulp in the spleens of OPE-treated group rats was increased compared with that in FSC group rats (P<0.05). Furthermore, blood lymphocyte numbers and IFN-γ, TNF-α, and IL-12 concentrations were significantly higher in OPE-fed groups than in FSC group (P<0.05). These results suggest that an OPE supplement can improve the immune status by increasing the number of immune-related cells and specific cytokine levels. PMID:25628726

  13. Onion peel water extracts enhance immune status in forced swimming rat model

    PubMed Central

    Lee, Hyun-A; Han, Sang-Jun; Hong, Sunhwa; Kim, Dong-Woo; Oh, Gi-Wook

    2014-01-01

    Onion peel contains a high concentration of quercetin and other flavonoids. In this study, the potential immune-enhancing effects of an onion peel water extract (OPE) supplement were investigated by the rat forced swimming test. OPE was prepared using hot water. Thirty-six male Sprague Dawley rats were fed a pellet diet for 1 week and were then randomly divided into six groups: normal control (NC), forced swimming control (FSC), positive control (quercetin 20 mg/kg), and three groups administered 4, 20, or 100 mg/kg of OPE. Oral drug administration was conducted daily for 4 weeks. All rats, except those of NC group, were forced to swim in water and were considered exhausted when they failed to rise to the water surface to breathe within a 7-s period. Blood lymphocyte counts, immune organ weights, histopathological analysis, and serum interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-12 levels were determined. OPE-treated rats consumed more food and had an increased thymic cortex to medulla ratio than that observed in FSC group rats (P<0.05). The area of the white pulp in the spleens of OPE-treated group rats was increased compared with that in FSC group rats (P<0.05). Furthermore, blood lymphocyte numbers and IFN-γ, TNF-α, and IL-12 concentrations were significantly higher in OPE-fed groups than in FSC group (P<0.05). These results suggest that an OPE supplement can improve the immune status by increasing the number of immune-related cells and specific cytokine levels. PMID:25628726

  14. Estrogen effects on the forced swim test differ in two outbred rat strains

    PubMed Central

    Koss, Wendy A.; Einat, Haim; Schloesser, Robert J.; Manji, Husseini K.; Rubinow, David R.

    2012-01-01

    Changes in reproductive hormones, such as estrogen, play a role in mood regulation. The present study examined strain differences (Long-Evans vs. Wistar-Hannover) in the behavioral and biochemical effects of estrogen manipulation. Adult ovariectomized female rats were treated with estradiol, vehicle, or withdrawn from estradiol. The two strains demonstrated differential behavioral responses to short-term estradiol administration in the forced swim test; estradiol induced an antidepressant-like effect in Long-Evans rats but not in Wistar rats. Conversely, withdrawal from estradiol resulted in a depressive-like state in the Wistar rats but not in the Long-Evans rats. Western blot analyses found no differences in estrogen receptors α and β within the hippocampus or the frontal cortex, two brain areas strongly implicated in affective disorders. These data demonstrate the importance of strain as a variable when interpreting behavioral effects of estrogen. PMID:22266677

  15. Commercially available Hypericum perforatum extracts do not decrease immobility of rats in the forced swimming test.

    PubMed

    Guilhermano, Luiz G; Ortiz, Luciana; Ferigolo, Maristela; Barros, Helena M T

    2004-01-01

    There are controversial results of clinical trials on the antidepressant effects of Hypericum perforatum, while several preclinical studies describe antidepressant properties for Hypericum extracts. This study evaluates the antidepressant effect of two commercially available hydroalcoholic extracts of H. perforatum standardized to contain 0.3% hypericin in comparison to imipramine (IMI), in the forced swimming test (FST). Wistar rats were treated with different doses of two Hypericum extracts, of hypericin or of IMI and submitted to the FST. The experiments were videotape recorded to detail immobile and active behaviors of rats during the procedures. The imported extract tested and hypericin did not modify rats' behaviors in the test, while IMI, a classical antidepressant, significantly shortened immobility and prolonged climbing behavior during forced swimming. The locally produced Hypericum extract significantly increased immobility duration as compared to the controls at the same time as climbing efforts were decreased. Therefore, the two different commercially available Brazilian hydroalcoholic H. perforatum extracts did not show the expected effects in a screening test for antidepressant agents, on the contrary, one of the extracts promoted a depressant-like effect in rats. Therefore, these extracts available to the population differ from other Hypericum extracts. At which step of the production or commercialization chain these extracts probably lost their therapeutic potential remains to be evaluated.

  16. Stressors can affect immobility time and response to imipramine in the rat forced swim test.

    PubMed

    Gutiérrez-García, Ana G; Contreras, Carlos M

    2009-02-01

    We subjected Wistar rats to the forced swim test (FST) to compare the effects of two doses of imipramine in physically stressed rats (P: unavoidable electric footshocks), emotionally stressed rats (E: odors), or non-stressed rats (C). Stress or control sessions lasted 35 days. Drug treatments began on day 21 and continued for the next 14 days. E rats were placed for 10 min, once per day for 35 days, in a small non-movement-restricting cage impregnated with urine collected from a P rat. E and P rats exhibited opposite changes in locomotion. After 21 days of stress sessions, P rats displayed the longest immobility times in the FST, followed by E rats. In the P group, on day 7 of treatment (day 28 of the study), imipramine (2.5 mg/kg) reduced immobility time to baseline values. In the E group, immobility time decreased only after 14 days of treatment with the low imipramine dose. The high dose of imipramine (5.0 mg/kg) reduced immobility time at day 7 of treatment in all groups. In conclusion, physical and emotional stress similarly increased immobility time in the FST, but emotional stress appears to be more resistant to imipramine treatment.

  17. Region- and sex-specific changes in CART mRNA in rat hypothalamic nuclei induced by forced swim stress.

    PubMed

    Balkan, Burcu; Gozen, Oguz; Koylu, Ersin O; Keser, Aysegul; Kuhar, Michael J; Pogun, Sakire

    2012-10-15

    Cocaine and amphetamine regulated transcript (CART) mRNA and peptides are highly expressed in the paraventricular (PVN), dorsomedial (DMH) and arcuate (ARC) nuclei of the hypothalamus. It has been suggested that these nuclei regulate the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system activity, and feeding behavior. Our previous studies showed that forced swim stress augmented CART peptide expression significantly in whole hypothalamus of male rats. In another study, forced swim stress increased the number of CART-immunoreactive cells in female PVN, whereas no effect was observed in male PVN or in the ARC nucleus of either sex. In the present study, we evaluated the effect of forced swim stress on CART mRNA expression in PVN, DMH and ARC nuclei in both male and female rats. Twelve male (stressed and controls, n=6 each) and 12 female (stressed and controls, n=6 each) Sprague-Dawley rats were used. Control animals were only handled, whereas forced swim stress procedure was applied to the stressed groups. Brains were dissected and brain sections containing PVN, DMH and ARC nuclei were prepared. CART mRNA levels were determined by in situ hybridization. In male rats, forced swim stress upregulated CART mRNA expression in DMH and downregulated it in the ARC. In female rats, forced swim stress increased CART mRNA expression in PVN and DMH, whereas a decrease was observed in the ARC nucleus. Our results show that forced swim stress elicits region- and sex-specific changes in CART mRNA expression in rat hypothalamus that may help in explaining some of the effects of stress.

  18. Effects of BNST lesions in female rats on forced swimming and navigational learning.

    PubMed

    Pezuk, Pinar; Aydin, Elif; Aksoy, Ayla; Canbeyli, Resit

    2008-09-01

    The bed nucleus of the stria terminalis (BNST) in the forebrain shows sexual dimorphism in its neuroanatomical connectivity and neurochemical characteristics. The structure is involved in many behavioral and motivational phenomena particularly related to coping with stress. Female rats differ from males in responding to stressful situations such as forced swimming and navigational learning in the water maze. It was previously shown that bilateral damage to the BNST in male Wistar rats aggravated depression as measured by forced swim tests, but did not impair navigational learning in the water maze. The present study extended the findings to female rats demonstrating that bilateral electrolytic lesions of the BNST increased immobility and decreased climbing compared to sham-operated controls, but failed to affect performance in the water maze. Additionally, lesions did not alter behavior in the open field and the elevated plus-maze tests suggesting not only that the modulation of depression by BNST lesions is specific, but also providing support for the view that the BNST may not necessarily be critically involved in anxiety.

  19. Nitric oxide modulates retention of immobility in the forced swimming test in rats.

    PubMed

    Jefferys, D; Funder, J

    1996-01-11

    Although originally developed as a possible screen for antidepressants, the Porsolt forced swimming test has more recently been extensively used as a model for studying the involvement of the endocrine system in the acquisition and retention of behavioural responses. In previous studies we have shown that while adrenalectomised rats acquire the immobile response normally, they are unable to retain it on retest next day. In the present study we show that retention of the immobile response in the Porsolt swim test is impaired in intact rats given the nitric oxide (NO) inhibitor L-N-arginine methyl ester (L-NAME), in a dose- and time-dependent manner. At a dose of 50 mg/kg levels of immobility are similar to those in adrenalectomised animals, an effect reversed by the simultaneous administration of L-arginine (50 mg/kg). L-Arginine also reverses the behavioural effect of adrenalectomy, and L-NAME blocks the ability of dexamethasone or the kappa-selective opioid ketocyclazocine to reverse the effect of adrenalectomy on retention of the immobile response. We conclude that the kappa-opioid and glucocorticoid mediated pathways previously shown to independently facilitate retention are mediated by nitric oxide.

  20. Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test.

    PubMed

    Cryan, John F; Valentino, Rita J; Lucki, Irwin

    2005-01-01

    Selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed antidepressant class today and exert their antidepressant-like effects by increasing synaptic concentrations of serotonin (5-HT). The rat forced swim test (FST) is the most widely used animal test predictive of antidepressant action. Procedural modifications recently introduced by our laboratory have enabled SSRI-induced behavioral responses to be measured in the modified FST. The use of this model to understand the pharmacological and physiological mechanisms underlying the role of 5-HT in the behavioral effects of antidepressant drugs is reviewed. Although all antidepressants reduced behavioral immobility, those antidepressants that increase serotonergic neurotransmission predominantly increase swimming behavior whereas those that increase catacholaminergic neurotransmission increase climbing behavior. The 5-HT(1A), 5-HT(1B/1D) and 5-HT(2C) receptors are the 5-HT receptors most important to the therapeutic effects of SSRIs, based on extensive evaluation of agonists and antagonists of individual 5-HT receptor subtypes. Studies involving chronic administration have shown that the effects of antidepressants are augmented following chronic treatment. Other studies have demonstrated strain differences in the response to serotonergic compounds. Finally, a physiological model of performance in the rat FST has been proposed involving the regulation of 5-HT transmission by corticotropin releasing factor (CRF).

  1. The modified forced-swim test in rats: influence of rope- or straw-suspension on climbing behavior.

    PubMed

    Nishimura, H; Tsuda, A; Ida, Y; Tanaka, M

    1988-01-01

    We modified Porsolt's forced-swim test by suspending ropes or straws above the water in order to investigate a possible relationship between immobility and perceived escape responses from water. In this modified test, it was demonstrated clearly that rats reduced their duration of immobility and attempted to climb up the suspended ropes or straws. Most rats which had remained immobile during a 5-min test period in the forced-swim test, exhibited such climbing responses within 5-10 min of rope-suspension. Despite the suspension of ropes, however, some rats showed immobile postures and did not respond to the rope. On the other hand, straws were used in order to produce sliding and prevent climbing when the animals attempted to climb. There were no differences in immobility during either rope- or straw-suspension. It seems that the climbing behavior displayed by forced-swimming rats is due to a "pseudo-escape" effect produced by the suspension of an object above the water. The present findings were interpreted as further evidence for the notion that immobility in forced-swimming rats does not necessarily imply "behavioral despair," but rather an emotional reaction to an inescapable stressor.

  2. Water temperature determines neurochemical and behavioural responses to forced swim stress: an in vivo microdialysis and biotelemetry study in rats.

    PubMed

    Linthorst, Astrid C E; Flachskamm, Cornelia; Reul, Johannes M H M

    2008-03-01

    Forced swimming is a behavioural stress model increasingly used to investigate the neurocircuitry of stress responses. Although forced swim stress clearly is a psychological stressor (anxiety, panic), its physical aspects are often neglected. There are indications that behavioural and neurochemical responses to swim stress depend on the water temperature. Thus, we investigated the responsiveness of hippocampal serotonergic neurotransmission (important in the coordination of stress responses), and of behaviour and core body temperature to forced swimming at different water temperatures (19, 25 and 35 degrees C). In vivo microdialysis and biotelemetry in freely-behaving rats were used. Dialysates were analysed for serotonin (5-HT) and its metabolite 5-HIAA (5-hydroxyindoleacetic acid) by HPLC with electrochemical detection. Forced swimming in water at 25 and 19 degrees C decreased core body temperature by 8 and 12 degrees C, respectively. A rapid and pronounced increase in hippocampal 5-HT and 5-HIAA was found in rats that swam at 35 degrees C, whereas biphasic responses in 5-HT and 5-HIAA were observed at 25 and 19 degrees C. Also swim stress behaviour and post-stress home cage behaviour depended on the water temperature. Comparing the serotonergic and core body temperature changes revealed that a combination of two different 5-HT and 5-HIAA responses seems to shape the neurotransmitter response. Swimming-induced increases in hippocampal extracellular concentrations of 5-HT and 5-HIAA occurred at all water temperatures, but these increases were temporarily quenched, or concentrations were transistently decreased, when core body temperature fell below 31 degrees C in water at 25 or 19 degrees C. These data demonstrate that water temperature is a key factor determining the impact of forced swim stress on behaviour and neurochemistry, and underscore that changes in these parameters should be interpreted in the light of the autonomic responses induced by this stressor

  3. Neural responses of rats in the forced swimming test: [F-18]FDG micro PET study.

    PubMed

    Jang, Dong-Pyo; Lee, So-Hee; Lee, Sang-Yoon; Park, Chan-Woong; Cho, Zang-Hee; Kim, Young-Bo

    2009-10-12

    The forced swimming test (FST) is a widely used tool in the assessment of behavioral despair and prediction of response to antidepressants. However, the neural mechanisms underlying behavioral changes between pretest and test sessions of the FST remain unclear. In this study, we investigated changes in rat brain activity during the FST using [F-18]Fluorodeoxyglucose micro PET. In both pretest and test sessions, the activity of the cerebellum and striatum increased, whereas significant deactivation was observed in the hippocampus, inferior colliculus, orbital cortex, and insula. The periaqueductal gray (PAG) region activated markedly in the pretest session, but did not activate in the test session. There was a significant increase in immobility and a decrease in climbing during the behavioral analysis test session. These results suggest that the PAG region may play an important role in the modulation of FST coping strategies subsequent to failure of the escape response during the pretest session.

  4. Adaptation of the pituitary-adrenal axis to daily repeated forced swim exposure in rats is dependent on the temperature of water.

    PubMed

    Rabasa, Cristina; Delgado-Morales, Raúl; Gómez-Román, Almudena; Nadal, Roser; Armario, Antonio

    2013-11-01

    Comparison of exposure to certain predominantly emotional stressors reveals a qualitatively similar neuroendocrine response profile as well as a reduction of physiological responses after daily repeated exposure (adaptation). However, particular physical components of the stressor may interfere with adaptation. As defective adaptation to stress can enhance the probability to develop pathologies, we studied in adult male rats (n = 10/group) swimming behavior (struggling, immobility and mild swim) and physiological responses (ACTH, corticosterone and rectal temperature) to daily repeated exposure to forced swim (20 min, 13 d) at 25 or 36 °C (swim25 or swim36). Rats were repeatedly blood-sampled by tail-nick and hormones measured by radioimmunoassay. Some differences were observed between the two swim temperature groups after the first exposure to forced swim: (a) active behaviors were greater in swim25 than swim36 groups; (b) swim25 but not swim36 caused hypothermia; and (c) swim36 elicited the same ACTH response as swim25, but plasma corticosterone concentration was lower for swim36 at 30 min post-swim. After daily repeated exposure, adaptation in ACTH secretion was observed with swim36 already on day 4, whereas with swim25 adaptation was not observed until day 13 and was of lower magnitude. Nevertheless, after repeated exposure to swim25 a partial protection from hypothermia was observed and the two swim conditions resulted in progressive reduction of active behaviors. Thus, daily repeated swim at 25 °C impairs adaptation of the hypothalamic-pituitary-adrenal axis as compared to swim at 36 °C, supporting the hypothesis that certain physical components of predominantly emotional stressors can interfere with the process of adaptation.

  5. Antioxidant and Antifatigue Properties of the Aqueous Extract of Moringa oleifera in Rats Subjected to Forced Swimming Endurance Test.

    PubMed

    Lamou, Bonoy; Taiwe, Germain Sotoing; Hamadou, André; Abene; Houlray, Justin; Atour, Mahamat Mey; Tan, Paul Vernyuy

    2016-01-01

    The effects of the aqueous extract of Moringa oleifera on swimming performance and related biochemical parameters were investigated in male Wistar rats (130-132 g). Four groups of rats (16 per group) were fed a standard laboratory diet and given distilled water, 100, 200, or 400 mg/kg of extract, respectively, for 28 days. On day 28, 8 rats from each group were subjected to the forced swimming test with tail load (10% of body weight). The remaining 8 rats per group were subjected to the 90-minute free swim. Maximum swimming time, glycemia, lactamia, uremia, triglyceridemia, hepatic and muscle glycogen, hematological parameters, and oxidative stress parameters (superoxide dismutase, catalase, reduced glutathione, and malondialdehyde) were measured. Results. M. oleifera extract increased maximum swimming time, blood hemoglobin, blood glucose, and hepatic and muscle glycogen reserves. The extract also increased the activity of antioxidant enzymes and decreased the blood concentrations of malondialdehyde. Furthermore, it decreased blood concentrations of lactate, triglycerides, and urea. In conclusion, the antifatigue properties of M. oleifera extract are demonstrated by its ability to improve body energy stores and tissue antioxidant capacity and to reduce the tissue build-up of lactic acid. PMID:26904162

  6. Antioxidant and Antifatigue Properties of the Aqueous Extract of Moringa oleifera in Rats Subjected to Forced Swimming Endurance Test

    PubMed Central

    Lamou, Bonoy; Taiwe, Germain Sotoing; Hamadou, André; Abene; Houlray, Justin; Atour, Mahamat Mey; Tan, Paul Vernyuy

    2016-01-01

    The effects of the aqueous extract of Moringa oleifera on swimming performance and related biochemical parameters were investigated in male Wistar rats (130–132 g). Four groups of rats (16 per group) were fed a standard laboratory diet and given distilled water, 100, 200, or 400 mg/kg of extract, respectively, for 28 days. On day 28, 8 rats from each group were subjected to the forced swimming test with tail load (10% of body weight). The remaining 8 rats per group were subjected to the 90-minute free swim. Maximum swimming time, glycemia, lactamia, uremia, triglyceridemia, hepatic and muscle glycogen, hematological parameters, and oxidative stress parameters (superoxide dismutase, catalase, reduced glutathione, and malondialdehyde) were measured. Results. M. oleifera extract increased maximum swimming time, blood hemoglobin, blood glucose, and hepatic and muscle glycogen reserves. The extract also increased the activity of antioxidant enzymes and decreased the blood concentrations of malondialdehyde. Furthermore, it decreased blood concentrations of lactate, triglycerides, and urea. In conclusion, the antifatigue properties of M. oleifera extract are demonstrated by its ability to improve body energy stores and tissue antioxidant capacity and to reduce the tissue build-up of lactic acid. PMID:26904162

  7. Individual differences in the forced swimming test and neurochemical kinetics in the rat brain.

    PubMed

    Sequeira-Cordero, Andrey; Mora-Gallegos, Andrea; Cuenca-Berger, Patricia; Fornaguera-Trías, Jaime

    2014-04-10

    Individual differences in the forced swimming test (FST) could be associated with differential temporal dynamics of gene expression and neurotransmitter activity. We tested juvenile male rats in the FST and classified the animals into those with low and high immobility according to the amount of immobility time recorded in FST. These groups and a control group which did not undergo the FST were sacrificed either 1, 6 or 24 h after the test. We analyzed the expression of the CRF, CRFR1, BDNF and TrkB in the prefrontal cortex, hippocampus and nucleus accumbens as well as norepinephrine, dopamine, serotonin, glutamate, GABA and glutamine in the hippocampus and nucleus accumbens. Animals with low immobility showed significant reductions of BDNF expression across time points in both the prefrontal cortex and the nucleus accumbens when compared with non-swim control. Moreover, rats with high immobility only showed a significant decrease of BDNF expression in the prefrontal cortex 6h after the FST. Regarding neurotransmitters, only accumbal dopamine turnover and hippocampal glutamate content showed an effect of individual differences (i.e. animals with low and high immobility), whereas nearly all parameters showed significant differences across time points. Correlational analyses suggest that immobility in the FST, probably reflecting despair, is related to prefrontal cortical BDNF and to the kinetics observed in several other neurochemical parameters. Taken together, our results suggest that individual differences observed in depression-like behavior can be associated not only with changes in the concentrations of key neurochemical factors but also with differential time courses of such factors. PMID:24518862

  8. Individual differences in the forced swimming test and neurochemical kinetics in the rat brain.

    PubMed

    Sequeira-Cordero, Andrey; Mora-Gallegos, Andrea; Cuenca-Berger, Patricia; Fornaguera-Trías, Jaime

    2014-04-10

    Individual differences in the forced swimming test (FST) could be associated with differential temporal dynamics of gene expression and neurotransmitter activity. We tested juvenile male rats in the FST and classified the animals into those with low and high immobility according to the amount of immobility time recorded in FST. These groups and a control group which did not undergo the FST were sacrificed either 1, 6 or 24 h after the test. We analyzed the expression of the CRF, CRFR1, BDNF and TrkB in the prefrontal cortex, hippocampus and nucleus accumbens as well as norepinephrine, dopamine, serotonin, glutamate, GABA and glutamine in the hippocampus and nucleus accumbens. Animals with low immobility showed significant reductions of BDNF expression across time points in both the prefrontal cortex and the nucleus accumbens when compared with non-swim control. Moreover, rats with high immobility only showed a significant decrease of BDNF expression in the prefrontal cortex 6h after the FST. Regarding neurotransmitters, only accumbal dopamine turnover and hippocampal glutamate content showed an effect of individual differences (i.e. animals with low and high immobility), whereas nearly all parameters showed significant differences across time points. Correlational analyses suggest that immobility in the FST, probably reflecting despair, is related to prefrontal cortical BDNF and to the kinetics observed in several other neurochemical parameters. Taken together, our results suggest that individual differences observed in depression-like behavior can be associated not only with changes in the concentrations of key neurochemical factors but also with differential time courses of such factors.

  9. Effects of chronic and acute stress on rat behaviour in the forced-swim test.

    PubMed

    Suvrathan, Aparna; Tomar, Anupratap; Chattarji, Sumantra

    2010-11-01

    Stress and depression may share common neural plasticity mechanisms. Importantly, the development and reversal of stress-induced plasticity requires time. These temporal aspects, however, are not captured fully in the forced-swim test (FST), a behavioural model for testing antidepressant efficacy, used originally in naïve animals. The present study probed whether and how a rodent model of stress affects behaviour in the FST over time. We found that the intensity and duration of stress are critical in the development of depressive symptoms in male Wistar rats (n = 37) as tested in the FST. Chronic immobilization stress (2 h/day for 10 days) elicited a range of responses, from low to high values of immobility in the FST on day 1, and subsequent immobility on day 2 was inversely related to individual day 1 values. As a whole, chronically stressed rats did not exhibit any significant change in immobility either on day 1 or day 2 compared to control rats. However, climbing behaviour was reduced uniformly from day 1 to day 2, despite the differences in immobility. In contrast, a separate group of rats (n = 30) subjected to the same chronic stressor displayed a significant reduction in open-arm exploration in the elevated plus maze, indicative of a robust increase in anxiety-like behaviour. Furthermore, when the 10-day chronic stress paradigm was reduced to a single 2-h episode of immobilization stress, it triggered a uniform day 1 to day 2 increase in immobility, which was not persistent 10 days later. These results highlight a need for closer examination of the ways in which stress-induced modulation of behaviour in the FST may be used and interpreted in future studies aimed at exploring connections between stress and depression.

  10. Stressors affect the response of male and female rats to clomipramine in a model of behavioral despair (forced swim test).

    PubMed

    Consoli, Daniele; Fedotova, Julia; Micale, Vincenzo; Sapronov, Nikolay S; Drago, Filippo

    2005-09-27

    Aim of the present study was to evaluate the effects of physical stressors (electric foot-shocks) on effect of the antidepressant drug, clomipramine and plasma corticosterone levels in male and female rats tested in a model of behavioral despair (forced swim test,). Male and female rats of the Wistar strain were injected with clomipramine (50 mg/kg, i.p.) or saline. A group of animals also received electric shocks of different intensity and duration of 24, 5 and 1 h before being subjected to forced swim test. At the end of behavioral procedures, vaginal smears were assessed in all female animals and data on immobility time were plotted according to the ovarian cycle phase. After decapitation, corticosterone plasma levels were measured by radioimmunoassay in both male and female rats. Application of mild shocks (5 ms, 0.1 mA) significantly reduced immobility time in forced swim test of untreated male rats and augmented clomipramine effect on this parameter. Moderate shocks of higher intensity or duration (5 ms, 1.0 mA) also resulted in decreased immobility time of untreated male rats, but in reduced effect of clomipramine treatment. Furthermore, application of severe shocks (10 ms, 1.0 mA) increased the immobility time in untreated animals and totally abolished clomipramine effect in forced swim test. Untreated non-shocked female rats in proestrous and estrous phases exhibited a longer immobility time as compared to diestrous animals. Immobility time appeared to be generally higher when mild, moderate or severe shocks were applied prior to behavioral testing in proestrous and estrous animals, while the behavioral response of diestrous and metestrous animals did not differ from that of controls. Clomipramine effect on immobility time was generally reduced by application of shocks of every strengths. Stress-induced plasma corticosterone levels surge correlated with intensity and duration of shocks in both male and female rats, but clomipramine treatment generally

  11. The centrally acting non-narcotic antitussive tipepidine produces antidepressant-like effect in the forced swimming test in rats.

    PubMed

    Kawaura, Kazuaki; Ogata, Yukino; Inoue, Masako; Honda, Sokichi; Soeda, Fumio; Shirasaki, Tetsuya; Takahama, Kazuo

    2009-12-14

    The antidepressant-like effect of tipepidine was studied in rats. Tipepidine at 20 and 40 mg/kg i.p. reduced immobility in the forced swimming test and tipepidine at 40 mg/kg, i.p. increased climbing in the test. The drug at 40 mg/kg, i.p. had no effect on the locomotor activity and motor coordination. These results suggest that tipepidine may be a novel drug with antidepressant-like activity.

  12. Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice.

    PubMed

    Castagné, Vincent; Moser, Paul; Roux, Sylvain; Porsolt, Roger D

    2011-04-01

    The development of antidepressants requires simple rodent behavioral tests for initial screening before undertaking more complex preclinical tests and clinical evaluation. Presented in the unit are two widely used screening tests used for antidepressants, the forced swim (also termed behavioral despair) test in the rat and mouse, and the tail suspension test in the mouse. These tests have good predictive validity and allow rapid and economical detection of substances with potential antidepressant-like activity. The behavioral despair and the tail suspension tests are based on the same principle: measurement of the duration of immobility when rodents are exposed to an inescapable situation. The majority of clinically used antidepressants decrease the duration of immobility. Antidepressants also increase the latency to immobility, and this additional measure can increase the sensitivity of the behavioral despair test in the mouse for certain classes of antidepressant. Testing of new substances in the behavioral despair and tail suspension tests allows a simple assessment of their potential antidepressant activity by the measurement of their effect on immobility.

  13. Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice.

    PubMed

    Castagné, Vincent; Moser, Paul; Roux, Sylvain; Porsolt, Roger D

    2010-06-01

    The development of antidepressants requires simple rodent behavioral tests for initial screening before undertaking more complex preclinical tests and clinical evaluation. Presented in the unit are two widely used screening tests used for antidepressants, the forced swim (also termed behavioral despair) test in the rat and mouse, and the tail suspension test in the mouse. These tests have good predictive validity and allow rapid and economical detection of substances with potential antidepressant-like activity. The behavioral despair and the tail suspension tests are based on the same principle: measurement of the duration of immobility when rodents are exposed to an inescapable situation. The majority of clinically used antidepressants decrease the duration of immobility. Antidepressants also increase the latency to immobility, and this additional measure can increase the sensitivity of the behavioral despair test in the mouse for certain classes of antidepressant. Testing of new substances in the behavioral despair and tail suspension tests allows a simple assessment of their potential antidepressant activity by the measurement of their effect on immobility.

  14. Antidepressant effects of curcumin in the forced swim test and olfactory bulbectomy models of depression in rats.

    PubMed

    Xu, Ying; Ku, Bao-Shan; Yao, Hai-Yan; Lin, Yan-Hua; Ma, Xing; Zhang, Yong-He; Li, Xue-Jun

    2005-09-01

    Curcuma longa is a major constituent of Xiaoyao-san, the traditional Chinese medicinal formula, which has been used to effectively manage stress and depression-related disorders in China. Curcumin is the active component of curcuma longa, and we hypothesized that curcumin would have an influence on depressive-like behaviors. The purpose of the present study was to confirm the putative antidepressant effect of chronic administrations of curcumin (1.25, 2.5, 5 and 10 mg/kg, p.o.) in the forced swimming test and bilateral olfactory bulbectomy (OB) models of depression in rats. In the first study, chronic treatment with curcumin (14 days) reduced the immobility time in the forced swimming test. In the second experiment, curcumin reversed the OB-induced behavioral abnormalities such as hyperactivity in the open field, as well as deficits in step-down passive avoidance. In addition, OB-induced low levels of serotonin (5-HT), noradrenaline (NA), high 5-hydroxyindoleacetic acid (5-HIAA) and 4-dihydroxyphenylacetic acid (DOPAC) in the hippocampus were observed, and were completely reversed by curcumin administration. A slight decrease in 5-HT, NA and dopamine (DA) levels was found in the frontal cortex of OB rats which was also reversed by curcumin treatment. These results confirm the antidepressant effects of curcumin in the forced swim and the OB models of depression in rats, and suggest that these antidepressant effects may be mediated by actions in the central monoaminergic neurotransmitter systems.

  15. Ontogeny and adolescent alcohol exposure in Wistar rats: open field conflict, light/dark box and forced swim test.

    PubMed

    Desikan, Anita; Wills, Derek N; Ehlers, Cindy L

    2014-07-01

    Epidemiological studies have demonstrated that heavy drinking and alcohol abuse and dependence peak during the transition between late adolescence and early adulthood. Studies in animal models have demonstrated that alcohol exposure during adolescence can cause a modification in some aspects of behavioral development, causing the "adolescent phenotype" to be retained into adulthood. However, the "adolescent phenotype" has not been studied for a number of behavioral tests. The objective of the present study was to investigate the ontogeny of behaviors over adolescence/young adulthood in the light/dark box, open field conflict and forced swim test in male Wistar rats. These data were compared to previously published data from rats that received intermittent alcohol vapor exposure during adolescence (AIE) to test whether they retained the "adolescent phenotype" in these behavioral tests. Three age groups of rats were tested (post-natal day (PD) 34-42; PD55-63; PD69-77). In the light/dark box test, younger rats escaped the light box faster than older adults, whereas AIE rats returned to the light box faster and exhibited more rears in the light than controls. In the open field conflict test, both younger and AIE rats had shorter times to first enter the center, spent more time in the center of the field, were closer to the food, and consumed more food than controls. In the forced swim test no clear developmental pattern emerged. The results of the light/dark box and the forced swim test do not support the hypothesis that adolescent ethanol vapor exposure can "lock-in" all adolescent phenotypes. However, data from the open field conflict test suggest that the adolescent and the AIE rats both engaged in more "disinhibited" and food motivated behaviors. These data suggest that, in some behavioral tests, AIE may result in a similar form of behavioral disinhibition to what is seen in adolescence. PMID:24785000

  16. Ontogeny and adolescent alcohol exposure in Wistar rats: open field conflict, light/dark box and forced swim test

    PubMed Central

    Desikan, Anita; Wills, Derek N.; Ehlers, Cindy L.

    2014-01-01

    Epidemiological studies have demonstrated that heavy drinking and alcohol abuse and dependence peak during the transition between late adolescence and early adulthood. Studies in animal models have demonstrated that alcohol exposure during adolescence can cause a modification in some aspects of behavioral development, causing the “adolescent phenotype” to be retained into adulthood. However, the “adolescent phenotype” has not been studied for a number of behavioral tests. The objective of the present study was to investigate the ontogeny of behaviors over adolescence/young adulthood in the light/dark box, open field conflict and forced swim test in male Wistar rats. These data were compared to previously published data from rats that received intermittent alcohol vapor exposure during adolescence (AIE) to test whether they retained the “adolescent phenotype” in these behavioral tests. Three age groups of rats were tested (post-natal day (PD) 34–42; PD55-63; PD69-77). In the light/dark box test, younger rats escaped the light box faster than older adults, whereas AIE rats returned to the light box faster and exhibited more rears in the light than controls. In the open field conflict test, both younger and AIE rats had shorter times to first enter the center, spent more time in the center of the field, were closer to the food, and consumed more food than controls. In the forced swim test no clear developmental pattern emerged. The results of the light/dark box and the forced swim test do not support the hypothesis that adolescent ethanol vapor exposure can “lock-in” all adolescent phenotypes. However, data from the open field conflict test suggest that the adolescent and the AIE rats both engaged in more “disinhibited” and food motivated behaviors. These data suggest that, in some behavioral tests, AIE may result in a similar form of behavioral disinhibition to what is seen in adolescence. PMID:24785000

  17. Ontogeny and adolescent alcohol exposure in Wistar rats: open field conflict, light/dark box and forced swim test.

    PubMed

    Desikan, Anita; Wills, Derek N; Ehlers, Cindy L

    2014-07-01

    Epidemiological studies have demonstrated that heavy drinking and alcohol abuse and dependence peak during the transition between late adolescence and early adulthood. Studies in animal models have demonstrated that alcohol exposure during adolescence can cause a modification in some aspects of behavioral development, causing the "adolescent phenotype" to be retained into adulthood. However, the "adolescent phenotype" has not been studied for a number of behavioral tests. The objective of the present study was to investigate the ontogeny of behaviors over adolescence/young adulthood in the light/dark box, open field conflict and forced swim test in male Wistar rats. These data were compared to previously published data from rats that received intermittent alcohol vapor exposure during adolescence (AIE) to test whether they retained the "adolescent phenotype" in these behavioral tests. Three age groups of rats were tested (post-natal day (PD) 34-42; PD55-63; PD69-77). In the light/dark box test, younger rats escaped the light box faster than older adults, whereas AIE rats returned to the light box faster and exhibited more rears in the light than controls. In the open field conflict test, both younger and AIE rats had shorter times to first enter the center, spent more time in the center of the field, were closer to the food, and consumed more food than controls. In the forced swim test no clear developmental pattern emerged. The results of the light/dark box and the forced swim test do not support the hypothesis that adolescent ethanol vapor exposure can "lock-in" all adolescent phenotypes. However, data from the open field conflict test suggest that the adolescent and the AIE rats both engaged in more "disinhibited" and food motivated behaviors. These data suggest that, in some behavioral tests, AIE may result in a similar form of behavioral disinhibition to what is seen in adolescence.

  18. The highly selective 5-hydroxytryptamine (5-HT)2A receptor antagonist, EMD 281014, significantly increases swimming and decreases immobility in male congenital learned helpless rats in the forced swim test.

    PubMed

    Patel, Jignesh G; Bartoszyk, Gerd D; Edwards, Emmeline; Ashby, Charles R

    2004-04-01

    We examined the effect of the highly selective 5-hydroxytryptamine (5-HT)(2A) receptor antagonist 7-[4-[2-(4-fluoro-phenyl)-ethyl]-piperazine-1-carbonyl]-1H-indole-3-carbonitrile HCl (EMD 281014) in congenital learned helpless male rats in the forced swim test. The administration of EMD-281014 (0.3-30 mg/kg i.p.) to congenital learned helpless rats dose-dependently and significantly (at 10 and 30 mg/kg) decreased immobility and increased swimming compared to vehicle-treated animals. Thus, EMD 281014 produces effects in the forced swim test resembling those of antidepressants.

  19. Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats.

    PubMed

    Kitagawa, Kouhei; Kitamura, Yoshihisa; Miyazaki, Toshiaki; Miyaoka, Junya; Kawasaki, Hiromu; Asanuma, Masato; Sendo, Toshiaki; Gomita, Yutaka

    2009-07-01

    The dopamine D2/D3 receptor agonist pramipexole has clinically been proven to improve depression or treatment-resistant depression. However, the involvement of the dopamine receptor system on the effect of pramipexole on depression remains unclear. We examined the influence of pramipexole on the duration of immobility during the forced swim test in normal and adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which pramipexole acts in this model was explored specifically in relation to the site of action through the use of microinjections into the intramedial prefrontal cortex and nucleus accumbens. Pramipexole (0.3-1 mg/kg) significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by L-741,626, a D2 receptor antagonist, and nafadotride, a D3 receptor antagonist, in normal rats. Furthermore, infusions of pramipexole into the intranucleus accumbens, but not the medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Taken together, the results of these experiments suggested that pramipexole, administered into the intranucleus accumbens rather than the medial prefrontal cortex, exerted an antidepressant-like effect on ACTH-treated rats via the dopaminergic system. The immobility-decreasing effect of pramipexole may be mediated by dopamine D2 and D3 receptors.

  20. Repeated forced swimming impairs prepulse inhibition and alters brain-derived neurotrophic factor and astroglial parameters in rats.

    PubMed

    Borsoi, Milene; Antonio, Camila Boque; Müller, Liz Girardi; Viana, Alice Fialho; Hertzfeldt, Vivian; Lunardi, Paula Santana; Zanotto, Caroline; Nardin, Patrícia; Ravazzolo, Ana Paula; Rates, Stela Maris Kuze; Gonçalves, Carlos-Alberto

    2015-01-01

    Glutamate perturbations and altered neurotrophin levels have been strongly associated with the neurobiology of neuropsychiatric disorders. Environmental stress is a risk factor for mood disorders, disrupting glutamatergic activity in astrocytes in addition to cognitive behaviours. Despite the negative impact of stress-induced neuropsychiatric disorders on public health, the molecular mechanisms underlying the response of the brain to stress has yet to be fully elucidated. Exposure to repeated swimming has proven useful for evaluating the loss of cognitive function after pharmacological and behavioural interventions, but its effect on glutamate function has yet to be fully explored. In the present study, rats previously exposed to repeated forced swimming were evaluated using the novel object recognition test, object location test and prepulse inhibition (PPI) test. In addition, quantification of brain-derived neurotrophic factor (BDNF) mRNA expression and protein levels, glutamate uptake, glutathione, S100B, GluN1 subunit of N-methyl-D-aspartate receptor and calmodulin were evaluated in the frontal cortex and hippocampus after various swimming time points. We found that swimming stress selectively impaired PPI but did not affect memory recognition. Swimming stress altered the frontal cortical and hippocampal BDNF expression and the activity of hippocampal astrocytes by reducing hippocampal glutamate uptake and enhancing glutathione content in a time-dependent manner. In conclusion, these data support the assumption that astrocytes may regulate the activity of brain structures related to cognition in a manner that alters complex behaviours. Moreover, they provide new insight regarding the dynamics immediately after an aversive experience, such as after behavioural despair induction, and suggest that forced swimming can be employed to study altered glutamatergic activity and PPI disruption in rodents. PMID:25444867

  1. Repeated forced swimming impairs prepulse inhibition and alters brain-derived neurotrophic factor and astroglial parameters in rats.

    PubMed

    Borsoi, Milene; Antonio, Camila Boque; Müller, Liz Girardi; Viana, Alice Fialho; Hertzfeldt, Vivian; Lunardi, Paula Santana; Zanotto, Caroline; Nardin, Patrícia; Ravazzolo, Ana Paula; Rates, Stela Maris Kuze; Gonçalves, Carlos-Alberto

    2015-01-01

    Glutamate perturbations and altered neurotrophin levels have been strongly associated with the neurobiology of neuropsychiatric disorders. Environmental stress is a risk factor for mood disorders, disrupting glutamatergic activity in astrocytes in addition to cognitive behaviours. Despite the negative impact of stress-induced neuropsychiatric disorders on public health, the molecular mechanisms underlying the response of the brain to stress has yet to be fully elucidated. Exposure to repeated swimming has proven useful for evaluating the loss of cognitive function after pharmacological and behavioural interventions, but its effect on glutamate function has yet to be fully explored. In the present study, rats previously exposed to repeated forced swimming were evaluated using the novel object recognition test, object location test and prepulse inhibition (PPI) test. In addition, quantification of brain-derived neurotrophic factor (BDNF) mRNA expression and protein levels, glutamate uptake, glutathione, S100B, GluN1 subunit of N-methyl-D-aspartate receptor and calmodulin were evaluated in the frontal cortex and hippocampus after various swimming time points. We found that swimming stress selectively impaired PPI but did not affect memory recognition. Swimming stress altered the frontal cortical and hippocampal BDNF expression and the activity of hippocampal astrocytes by reducing hippocampal glutamate uptake and enhancing glutathione content in a time-dependent manner. In conclusion, these data support the assumption that astrocytes may regulate the activity of brain structures related to cognition in a manner that alters complex behaviours. Moreover, they provide new insight regarding the dynamics immediately after an aversive experience, such as after behavioural despair induction, and suggest that forced swimming can be employed to study altered glutamatergic activity and PPI disruption in rodents.

  2. Prior cold water swim stress alters immobility in the forced swim test and associated activation of serotonergic neurons in the rat dorsal raphe nucleus.

    PubMed

    Drugan, R C; Hibl, P T; Kelly, K J; Dady, K F; Hale, M W; Lowry, C A

    2013-12-01

    Prior adverse experience alters behavioral responses to subsequent stressors. For example, exposure to a brief swim increases immobility in a subsequent swim test 24h later. In order to determine if qualitative differences (e.g. 19°C versus 25°C) in an initial stressor (15-min swim) impact behavioral, physiological, and associated neural responses in a 5-min, 25°C swim test 24h later, rats were surgically implanted with biotelemetry devices 1 week prior to experimentation then randomly assigned to one of six conditions (Day 1 (15 min)/Day 2 (5 min)): (1) home cage (HC)/HC, (2) HC/25°C swim, (3) 19°C swim/HC, (4) 19°C swim/25°C swim, (5) 25°C swim/HC, (6) 25°C swim/25°C swim. Core body temperature (Tb) was measured on Days 1 and 2 using biotelemetry; behavior was measured on Day 2. Rats were transcardially perfused with fixative 2h following the onset of the swim on Day 2 for analysis of c-Fos expression in midbrain serotonergic neurons. Cold water (19°C) swim on Day 1 reduced Tb, compared to both 25°C swim and HC groups on Day 1, and, relative to rats exposed to HC conditions on Day 1, reduced the hypothermic response to the 25°C swim on Day 2. The 19°C swim on Day 1, relative to HC exposure on Day 1, increased immobility during the 5-min swim on Day 2. Also, 19°C swim, relative to HC conditions, on Day 1 reduced swim (25°C)-induced increases in c-Fos expression in serotonergic neurons within the dorsal and interfascicular parts of the dorsal raphe nucleus. These results suggest that exposure to a 5-min 19°C cold water swim, but not exposure to a 5-min 25°C swim alters physiological, behavioral and serotonergic responses to a subsequent stressor.

  3. Influence of enrichment on behavioral and neurogenic effects of antidepressants in Wistar rats submitted to repeated forced swim test.

    PubMed

    Possamai, Fernanda; dos Santos, Juliano; Walber, Thais; Marcon, Juliana C; dos Santos, Tiago Souza; Lino de Oliveira, Cilene

    2015-04-01

    Repeated forced swimming test (rFST) may detect gradual effects of antidepressants in adult rats. Antidepressants, as enrichment, affected behavior and neurogenesis in rats. However, the influence of enrichment on behavioral and neurogenic effects of antidepressants is unknown. Here, effects of antidepressants on rFST and hippocampal neurogenesis were investigated in rats under enriched conditions. Behaviors of male Wistar rats, housed from weaning in standard (SE) or enriched environment (EE), were registered during rFST. The rFST consisted of 15min of swimming (pretest) followed by 5min of swimming in the first (test), seventh (retest 1) and fourteenth (retest 2) days after pretest. One hour before the test, rats received an intraperitoneal injection of saline (1ml/kg), fluoxetine (2.5mg/kg) or imipramine (2.5 or 5mg/kg). These treatments were performed daily until the day of the retest 2. After retest 2, rats were euthanized for the identification of markers for neurogenesis in the hippocampus. Fluoxetine or imipramine decreased immobility in retests 1 and 2, as compared to saline. EE abolished these differences. In EE, fluoxetine or imipramine (5mg/kg) reduced immobility time in retest 2, as compared to the test. Independent of the housing conditions, fluoxetine and imipramine (5mg/kg) increased the ratio of immature neurons per progenitor cell in the hippocampus. In summary, antidepressants or enrichment counteracted the high immobility in rFST. Enrichment changed the effects of antidepressants in rFST depending on the type, and the dose of a substance but failed to change neurogenesis in control or antidepressant treated-rats. Effects of antidepressants and enrichment on rFST seemed neurogenesis-independent.

  4. The swim force as a body force

    NASA Astrophysics Data System (ADS)

    Yan, Wen; Brady, John

    2015-11-01

    Net (as opposed to random) motion of active matter results from an average swim (or propulsive) force. It is shown that the average swim force acts like a body force - an internal body force [Yan and Brady, Soft Matter, DOI:10.1039/C5SM01318F]. As a result, the particle-pressure exerted on a container wall is the sum of the swim pressure [Takatori et al., Phys. Rev. Lett., 2014, 113, 028103] and the `weight' of the active particles. A continuum mechanical description is possible when variations occur on scales larger than the run length of the active particles and gives a Boltzmann-like distribution from a balance of the swim force and the swim pressure. Active particles may also display `action at a distance' and accumulate adjacent to (or be depleted from) a boundary without any external forces. In the momentum balance for the suspension - the mixture of active particles plus fluid - only external body forces appear.

  5. Behavior in the forced swim test and neurochemical changes in the hippocampus in young rats after 2-week zinc deprivation.

    PubMed

    Tamano, Haruna; Kan, Fumika; Kawamura, Mika; Oku, Naoto; Takeda, Atsushi

    2009-12-01

    Abnormal behavior in zinc deficiency and its cause are poorly understood. In the present paper, behavior in the forced swim test and neurochemical changes in the brain associated with its behavior were studied focused on abnormal corticosterone secretion in zinc deficiency. The effect of chronic corticosterone treatment was also studied. Immobility time in the forced swim test was increased in young rats fed a zinc-deficient diet for 2 weeks, as well as corticosterone (40mg/kg/dayx14 days)-treated control rats. The basal Ca(2+) levels in the hippocampus, which were determined by fluo-4FF, AM, were increased in both brain slices from zinc-deficient and corticosterone-treated rats. Serum glucose level was decreased in zinc deficiency and hippocampal glucose metabolism, which is determined by [(14)C]2-deoxyglucose uptake, was elevated. Hippocampal ATP level was not decreased, whereas, the concentrations of glutamate, GABA and glutamine in the hippocampus, unlike the whole brain, were decreased in zinc deficiency. However, the decrease in these amino acids was restored by adrenalectomy prior to zinc deficiency. These results suggest that glucose is insufficient for the synthesis of amino acids in the hippocampus of zinc-deficient rats. It is likely that the neurochemical and metabolic changes in the hippocampus, which may be associated with abnormal corticosterone secretion, is the base of abnormal behavior associated with neuropsychological symptoms in zinc deficiency. PMID:19463882

  6. Differential Rearing Alters Forced Swim Test Behavior, Fluoxetine Efficacy, and Post-Test Weight Gain in Male Rats.

    PubMed

    Arndt, David L; Peterson, Christy J; Cain, Mary E

    2015-01-01

    Environmental factors play a key role in the etiology of depression. The rodent forced swim test (FST) is commonly used as a preclinical model of depression, with increases in escape-directed behavior reflecting antidepressant effects, and increases in immobility reflecting behavioral despair. Environmental enrichment leads to serotonergic alterations in rats, but it is unknown whether these alterations may influence the efficacy of common antidepressants. Male Sprague-Dawley rats were reared in enriched (EC), standard (SC), or isolated (IC) conditions. Following the rearing period, fluoxetine (10 or 20 mg/kg, i.p.) was administered 23.5 hrs, 5 hrs, and 1 hr before locomotor and FST measures. Following locomotor testing and FST exposure, rats were weighed to assess fluoxetine-, FST-, and environmental condition-induced moderations in weight gain. Results revealed an antidepressant effect of environmental enrichment and a depressant effect of isolation. Regardless of significant fluoxetine effects on locomotor activity, fluoxetine generally decreased swimming and increased immobility in all three environmental conditions, with IC-fluoxetine (10 mg/kg) rats and EC-fluoxetine (20 mg/kg) rats swimming less than vehicle counterparts. Subchronic 20 mg/kg fluoxetine also induced significant weight loss, and differential rearing appeared to moderate weight gain following FST stress. These results suggest that differential rearing has the ability to alter FST behaviors, fluoxetine efficacy, and post-stressor well-being. Moreover, 20 mg/kg fluoxetine, administered subchronically, may lead to atypical effects of those commonly observed in the FST, highlighting the importance and impact of both environmental condition and dosing regimen in common animal models of depression.

  7. Swimming-based pica in rats.

    PubMed

    Nakajima, Sadahiko

    2016-09-01

    We have recently demonstrated that voluntary or forced running in activity wheels yields pica behavior (kaolin clay intake) in rats (Nakajima, 2016; Nakajima and Katayama, 2014). The present study provides experimental evidence that a single 40-min session of swimming in water also generates pica in rats, while showering rats with water does not produce such behavior. Because kaolin intake has been regarded as a measure of nausea in rats, this finding suggests that swimming activity, as well as voluntary or forced running, induces nausea in rats. PMID:27370361

  8. Repeated forced swim stress differentially affects formalin-evoked nociceptive behaviour and the endocannabinoid system in stress normo-responsive and stress hyper-responsive rat strains.

    PubMed

    Jennings, Elaine M; Okine, Bright N; Olango, Weredeselam M; Roche, Michelle; Finn, David P

    2016-01-01

    Repeated exposure to a homotypic stressor such as forced swimming enhances nociceptive responding in rats. However, the influence of genetic background on this stress-induced hyperalgesia is poorly understood. The aim of the present study was to compare the effects of repeated forced swim stress on nociceptive responding in Sprague-Dawley (SD) rats versus the Wistar Kyoto (WKY) rat strain, a genetic background that is susceptible to stress, negative affect and hyperalgesia. Given the well-documented role of the endocannabinoid system in stress and pain, we investigated associated alterations in endocannabinoid signalling in the dorsal horn of the spinal cord and amygdala. In SD rats, repeated forced swim stress for 10 days was associated with enhanced late phase formalin-evoked nociceptive behaviour, compared with naive, non-stressed SD controls. In contrast, WKY rats exposed to 10 days of swim stress displayed reduced late phase formalin-evoked nociceptive behaviour. Swim stress increased levels of monoacylglycerol lipase (MAGL) mRNA in the ipsilateral side of the dorsal spinal cord of SD rats, an effect not observed in WKY rats. In the amygdala, swim stress reduced anandamide (AEA) levels in the contralateral amygdala of SD rats, but not WKY rats. Additional within-strain differences in levels of CB1 receptor and fatty acid amide hydrolase (FAAH) mRNA and levels of 2-arachidonylglycerol (2-AG) were observed between the ipsilateral and contralateral sides of the dorsal horn and/or amygdala. These data indicate that the effects of repeated stress on inflammatory pain-related behaviour are different in two rat strains that differ with respect to stress responsivity and affective state and implicate the endocannabinoid system in the spinal cord and amygdala in these differences.

  9. Antidepressant-like effects of rosiglitazone, a PPARγ agonist, in the rat forced swim and mouse tail suspension tests.

    PubMed

    Eissa Ahmed, Amany Ali; Al-Rasheed, Nawal Mohammed; Al-Rasheed, Nouf Mohammed

    2009-10-01

    Several studies have evaluated thiazolidinedione therapy as medical treatments for some central nervous system disorders, such as cognitive deficits associated with neurodegenerative disorders. However, there is limited data to support a direct role for peroxisome proliferator-activated receptor-γ agonists in depression. Therefore, the aim of this study was to investigate antidepressant-like activity of rosiglitazone using the mouse tail suspension test and the rat forced swimming test, two models sensitive to the effects of antidepressants. In the tail suspension test, 5 days of treatment with rosiglitazone (8.5 or 17 mg/kg, orally) reduced immobility time. In the forced swimming test, rosiglitazone (6 or 12 mg/kg, orally) treatment decreased immobility time and increased climbing. These effects were not accompanied by any alteration in locomotor activity in the open field test. Rosiglitazone treatment (6 or 12 mg/kg, orally) significantly reduced plasma corticosterone levels in rats. GW9662 significantly inhibited the rosiglitazone-induced reduction in the duration of immobility. In summary, this study suggests that rosiglitazone possesses a specific antidepressant-like activity in behavioral models and that this effect may be mediated by reduction of plasma corticosterone level.

  10. Antidepressant-Like Effects of Lindera obtusiloba Extracts on the Immobility Behavior of Rats in the Forced Swim Test.

    PubMed

    Lim, Dong Wook; Lee, Mi-Sook; Her, Song; Cho, Suengmok; Lee, Chang-Ho; Kim, In-Ho; Han, Daeseok

    2016-02-27

    Lindera obtusiloba extracts are commonly used as an alternative medicine due to its numerous health benefits in Korea. However, the antidepressant-like effects of L. obtusiloba extracts have not been fully elucidated. In this study, we aimed to determine whether L. obtusiloba extracts exhibited antidepressant-like activity in rats subjected to forced swim test (FST)-induced depression. Acute treatment of rats with L. obtusiloba extracts (200 mg/kg, p.o.) significantly reduced immobility time and increased swimming time without any significant change in climbing. Rats treated with L. obtusiloba extracts also exhibited a decrease in the limbic hypothalamic-pituitary-adrenal (HPA) axis response to the FST, as indicated by attenuation of the corticosterone response and decreased c-Fos immunoreactivity in the hippocampus CA3 region. In addition, L. obtusiloba extracts, at concentrations that were not affected by cell viability, significantly decreased luciferase activity in response to cortisol in a concentration-dependent manner by the glucocorticoid binding assay in HeLa cells. Our findings suggested that the antidepressant-like effects of L. obtusiloba extracts were likely mediated via the glucocorticoid receptor (GR). Further studies are needed to evaluate the potential of L. obtusiloba extracts as an alternative therapeutic approach for the treatment of depression.

  11. The comparison of immobility time in experimental rat swimming models.

    PubMed

    Calil, Caroline Morini; Marcondes, Fernanda Klein

    2006-09-27

    Rat swimming models have been used in studies about stress and depression. However, there is no consensus about interpreting immobility (helplessness or adaptation) in the literature. In the present study, immobility time, glucose and glycogen mobilization, corticosterone and the effect of desipramine and diazepam were investigated in two different models: swimming stress and the forced swimming test. Immobility time was lower in swimming stress than in the forced swimming test. Both swimming models increased corticosterone levels in comparison with control animal levels. Moreover, swimming stress induced higher corticosterone levels than the forced swimming test did [F(2,14)=59.52; p<0.001]. Liver glycogen content values differed from one another (swimming stress<forced swimming testswimming stress in comparison with the forced swimming test and control. The immobility time was recorded and measured in another group treated with desipramine and diazepam in two protocols: a single session of forced swimming test or swimming stress and two sessions (pre- and retest) of forced swimming model or swimming stress. Desipramine decreased the immobility time in the forced swimming test in both the single [F(2,25)=20.63; p<0.0001] and retest [F(2,37)=7.28; p=0.002] swimming session, without changes in the swimming stress model. Diazepam increased the immobility time in the swimming stress but not in the forced swimming test during the single [F(2,26)=11.24; p=0.0003] and retest sessions [F(2,38)=4.17; p=0.02]. It was concluded that swimming stress and the forced swimming test induced different behavior, hormonal and metabolic responses and represented different situations to the animal.

  12. Changes in c-Fos Expression in the Forced Swimming Test: Common and Distinct Modulation in Rat Brain by Desipramine and Citalopram

    PubMed Central

    Choi, Sun Hye; Chung, Sung; Cho, Jin Hee; Cho, Yun Ha; Kim, Jin Wook; Kim, Jeong Min; Kim, Hee Jeong; Kim, Hyun Ju

    2013-01-01

    Rodents exposed to a 15-min pretest swim in the forced swimming test (FST) exhibit prolonged immobility in a subsequent 5-min test swim, and antidepressant treatment before the test swim reduces immobility. At present, neuronal circuits recruited by antidepressant before the test swim remain unclear, and also less is known about whether antidepressants with different mechanisms of action could influence neural circuits differentially. To reveal the neural circuits associated with antidepressant effect in the FST, we injected desipramine or citalopram 0.5 h, 19 h, and 23 h after the pretest swim and observed changes in c-Fos expression in rats before the test swim, namely 24 h after the pretest swim. Desipramine treatment alone in the absence of pretest swim was without effect, whereas citalopram treatment alone significantly increased the number of c-Fos-like immunoreactive cells in the central nucleus of the amygdala and bed nucleus of the stria terminalis, where this pattern of increase appears to be maintained after the pretest swim. Both desipramine and citalopram treatment after the pretest swim significantly increased the number of c-Fos-like immunoreactive cells in the ventral lateral septum and ventrolateral periaqueductal gray before the test swim. These results suggest that citalopram may affect c-Fos expression in the central nucleus of the amygdala and bed nucleus of the stria terminalis distinctively and raise the possibility that upregulation of c-Fos in the ventral lateral septum and ventrolateral periaqueductal gray before the test swim may be one of the probable common mechanisms underlying antidepressant effect in the FST. PMID:23946692

  13. Synergistic interaction between ketoconazole and several antidepressant drugs with allopregnanolone treatments in ovariectomized Wistar rats forced to swim.

    PubMed

    Molina-Hernández, Miguel; Tellez-Alcántara, Norma Patricia; García, Julían Pérez; Lopez, Jorge Ivan Olivera; Jaramillo, M Teresa

    2004-12-01

    This article was aimed to investigate the interest of the combination allopregnanolone plus ketoconazole in depression with the time-sampling method in the forced swimming task. Dose-response curves for fluoxetine (0.5, 1.0 or 2.0 mg/kg, twice day, during 2 weeks; i.p.), desipramine (0.5, 1.0 or 2.14 mg/kg, twice a day, during 2 weeks; i.p.), ketoconazole (6.25, 12.5, 25.0 and 37.5 mg/kg, once a day, during 2 weeks; i.p.) and allopregnanolone (0.5, 1.5, 2.0 mg/kg; once a day, during 2 weeks; s.c.) were established. Fluoxetine (1.0 mg/kg, p < 0.05; 2.0 mg/kg, p < 0.05) or ketoconazole (25.0 mg/kg, p < 0.05; 37.5 mg/kg, p < 0.05) produced antidepressant-like behavioral changes in swimming, highlighting a serotonergic mechanism while desipramine (1.0 mg/kg, p < 0.05; 2.14 mg/kg, p < 0.05) or allopregnanolone (1.5 mg/kg, p < 0.05; 2.0 mg/kg, p < 0.05) increased climbing behavior highlighting noradrenergic or dopaminergic effects. Subthreshold doses of fluoxetine (p < 0.05), desipramine (p < 0.05) or ketoconazole (p < 0.05) synergized with subthreshold doses of allopregnanolone and reduced immobility by increasing climbing. In conclusion, fluoxetine, desipramine, ketoconazole and allopregnanolone produced differential antidepressant-like actions in ovariectomized rats forced to swim. Ketoconazole, fluoxetine or desipramine synergized with allopregnanolone.

  14. The Mouse Forced Swim Test

    PubMed Central

    Can, Adem; Dao, David T.; Arad, Michal; Terrillion, Chantelle E.; Piantadosi, Sean C.; Gould, Todd D.

    2012-01-01

    The forced swim test is a rodent behavioral test used for evaluation of antidepressant drugs, antidepressant efficacy of new compounds, and experimental manipulations that are aimed at rendering or preventing depressive-like states. Mice are placed in an inescapable transparent tank that is filled with water and their escape related mobility behavior is measured. The forced swim test is straightforward to conduct reliably and it requires minimal specialized equipment. Successful implementation of the forced swim test requires adherence to certain procedural details and minimization of unwarranted stress to the mice. In the protocol description and the accompanying video, we explain how to conduct the mouse version of this test with emphasis on potential pitfalls that may be detrimental to interpretation of results and how to avoid them. Additionally, we explain how the behaviors manifested in the test are assessed. PMID:22314943

  15. The mouse forced swim test.

    PubMed

    Can, Adem; Dao, David T; Arad, Michal; Terrillion, Chantelle E; Piantadosi, Sean C; Gould, Todd D

    2012-01-29

    The forced swim test is a rodent behavioral test used for evaluation of antidepressant drugs, antidepressant efficacy of new compounds, and experimental manipulations that are aimed at rendering or preventing depressive-like states. Mice are placed in an inescapable transparent tank that is filled with water and their escape related mobility behavior is measured. The forced swim test is straightforward to conduct reliably and it requires minimal specialized equipment. Successful implementation of the forced swim test requires adherence to certain procedural details and minimization of unwarranted stress to the mice. In the protocol description and the accompanying video, we explain how to conduct the mouse version of this test with emphasis on potential pitfalls that may be detrimental to interpretation of results and how to avoid them. Additionally, we explain how the behaviors manifested in the test are assessed.

  16. Melatonin affects the immobility time of rats in the forced swim test: the role of serotonin neurotransmission.

    PubMed

    Micale, Vincenzo; Arezzi, Anna; Rampello, Liborio; Drago, Filippo

    2006-10-01

    The efficacy of melatonin or its derivatives in depressive patients has been recently considered for clinical application. However, the evidence for its effect on experimental models of depression is not consolidated. Here, the effects of melatonin on the model of forced swim test (FST) paradigm were studied in male rats of the Wistar strain after acute intraperitoneal (i.p.) administration of 0.1, 0.5 or 1 mg/kg of the hormone. Melatonin at doses of 0.5 and 1 mg/kg, but not of 0.1 mg/kg, decreased the immobility of rats in the FST paradigm suggesting a possible antidepressant-like activity. The dose of 0.5 mg/kg appeared to be as potent as clomipramine 50 mg/kg in reducing the immobility time of rats in the FST paradigm. The effect of melatonin on immobility time of rats in the FST paradigm was abolished by the simultaneous injection of the non-selective melatonin antagonist, luzindole (0.25 mg/kg, subcutaneously). Similarly, administration of small quantities of serotonin (5-HT, 5 ng/1 microl) or of the 5-HT(2A)/5-HT(2C) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (2 ng/1 microl) injected into the amygdale totally suppressed the reduction of immobility time in the FST paradigm induced by melatonin 0.5 mg/kg. These results may suggest that effects of melatonin on the behavioral reaction of rats in the FST paradigm are due to an interaction of the hormone with central 5-HT neurotransmission.

  17. Acute treatment with 5-HT3 receptor antagonist, tropisetron, reduces immobility in intact female rats exposed to the forced swim test.

    PubMed

    Bravo, Gabriela; Maswood, Sharmin

    2006-10-01

    The effects of tropisetron, a 5-HT3 receptor antagonist, were evaluated in adult Fischer female rats exposed to the Forced Swim Test (FST). Rats selected on the days of proestrus or estrus was immersed in a cylinder of water for 2 consecutive days. Rats were exposed to the FST for 15 min on day 1 (pretest), followed by a 5-min session (test), 24 h later. The proestrous-estrous group consisted of rats that were exposed to the FST on their proestrous stage (pretest); then 24 h later the same rats were exposed to the FST on their estrous stage (test). Rats in the estrous-diestrous group were exposed to the FST on their estrous stage (pretest) and 24 h later on their diestrous stage (test). Rats were injected intraperitoneally with saline or 1.0 or 2.0 mg/kg tropisetron 30 min prior to exposure to the cylinder on the test day. Immobility, swimming, and struggling behaviors were scored for 5 min. There was a significant decline in immobility after treatment with 2.0 mg/kg tropisetron in both groups. In addition, a significant decline in swimming was observed in the estrous rats (proestrous-estrous group) after treatment with 2.0 mg/kg tropisetron. There were no significant effects of tropisetron on struggling in any groups examined.

  18. Comparison of monoamine reuptake inhibitors for the immobility time and serotonin levels in the hippocampus and plasma of sub-chronically forced swim stressed rats.

    PubMed

    Abbas, Ghulam; Naqvi, Sabira; Dar, Ahsana

    2012-04-01

    The current study was aimed at comparing the behavioral and biochemical (5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels) effects of monoamine reuptake inhibitors (fluoxetine, venlafaxine and imipramine) in sub-chronically forced swim stressed rats. At the given doses of 10, 20 and 30 mg/kg, among aforesaid antidepressants, the imipramine treatment alone caused significant decline in the immobility time of rats (IC(50) 20 mg/kg). In the hippocampus of rats, the imipramine treatment caused significant elevation of 5-hydroxytryptamine (5-HT) whereas, the fluoxetine and venlafaxine elicited significant increase in 5-hydroxyindoleacetic acid (5-HIAA) levels. Likewise, in the plasma of rats, the imipramine treatment significantly increased the 5-HIAA levels whereas, the fluoxetine and venlafaxine treatment significantly elevate the 5-HT levels. It can therefore be inferred that the imipramine did not act like other monoamine reuptake inhibitors in biochemical study, which could possibly underlie its ability to be detected in forced swim test (behavioral study). Moreover, the re-uptake inhibition of 5-HT is not accountable for the antidepressant action exhibited in forced swim test.

  19. Sertraline behavioral response associates closer and dose-dependently with cortical rather than hippocampal serotonergic activity in the rat forced swim stress.

    PubMed

    Mikail, Hudu G; Dalla, Christina; Kokras, Nikolaos; Kafetzopoulos, Vasilios; Papadopoulou-Daifoti, Z

    2012-09-10

    The rat Forced Swim Test (FST) is widely used to investigate the response to antidepressant treatment. Selective serotonin reuptake inhibitors (SSRIs) elongate swimming duration during the FST, while climbing duration is unaffected. In the present study, we aimed to correlate behavioral effects of the SSRI sertraline in the FST with respective changes in the serotonergic activity of the hippocampus and the prefrontal cortex. Male rats were subjected to the standard FST (two swim sessions in two consecutive days) and between the two sessions they received three i.p. injections of sertraline (10 mg/kg or 40 mg/kg) or vehicle. All rats were killed immediately after the second FST session. Unstressed animals received the same administration schemes and were killed in equivalent time-points. Serotonin and its metabolite 5-HIAA were assayed in the hippocampus and the prefrontal cortex with the use of high-performance liquid chromatography (HPLC-ED) and their ratio 5-HIAA/5-HT was calculated. Sertraline enhanced swimming and decreased immobility duration at both doses. Serotonergic activity was not altered by the 2-day swim stress in either brain region, while subchronic sertraline treatment enhanced 5-HT levels and decreased 5-HIAA/5-HT in the hippocampus and the prefrontal cortex. The serotonin turnover rate (5-HIAA/5-HT ratio) decrease is probably indicative of reduced 5-HT metabolism, as a result of 5-HT reuptake inhibition. This effect was significant in the prefrontal cortex of unstressed rats only after a higher dose of sertraline. In the prefrontal cortex, but not in the hippocampus, immobility duration was negatively correlated with 5-HT tissue levels, whereas swimming duration was positively correlated with 5-HT. These results indicate that after antidepressant treatment, behavior during the FST can be predictive of respective serotonergic changes, especially in the prefrontal cortex.

  20. Allopregnanolone reduces immobility in the forced swimming test and increases the firing rate of lateral septal neurons through actions on the GABAA receptor in the rat.

    PubMed

    Rodrìguez-Landa, Juan Francisco; Contreras, Carlos M; Bernal-Morales, Blandina; Gutièrrez-Garcìa, Ana G; Saavedra, Margarita

    2007-01-01

    Since allopregnanolone reduces the total time of immobility in rats submitted to the forced swimming test, we decided to explore whether this neuroactive steroid shares other antidepressant-like actions, such as increasing the neuronal firing rate in the lateral septal nucleus (LSN). In order to discard the influence of the oestrous cycle on immobility and on the firing rate of LSN neurons, all Wistar rats used in the study underwent ovariectomy before treatments. A group of rats received different doses of allopregnanolone (0.5, 1.0, 2.0 and 3.0 mg/kg, i.p.) 1 hour before being forced to swim in order to identify the minimum effective dose diminishing immobility. None of the tested doses of allopregnanolone produced significant changes in motor activity in the open-field test. The minimum dose of allopregnanolone producing a significant reduction in the total time of immobility (p<0.05) against the vehicle was 1.0 mg/kg, while 2.0 mg/kg and above also increased the latency to the first period of immobility (p<0.05). The minimum effective dose of allopregnanolone reducing immobility in the forced swimming test (1.0 mg/kg) significantly (p <0.05) produced a higher (twofold) neuronal firing rate in LSN neurons, but did not produce any change in septofimbrial nucleus neurons, which fired at a rate similar to that of vehicle-treated rats. The pretreatment with the non-competitive GABAA receptor antagonist, picrotoxin (1.0 mg/kg), blocked the aforementioned actions of allopregnanolone on both immobility and LSN firing rate. In conclusion, allopregnanolone produces an antidepressant-like effect in the forced swimming test, associated with an increase in the LSN neuronal firing rate, seemingly mediated by the GABAA receptor.

  1. Effect of prenatal forced-swim stress and morphine co-administration on pentylentetrazol-induced epileptic behaviors in infant and prepubertal rats.

    PubMed

    Ebrahimi, Loghman; Saboory, Ehsan; Roshan-Milani, Shiva; Hashemi, Paria

    2014-09-01

    Prenatal exposure to stress and morphine has complicated effects on epileptic seizure. Many reports have shown an interaction between morphine- and stress-induced behavioral changes in adult rats. In the present study, effect of prenatal forced-swim stress and morphine co-administration on pentylentetrazole (PTZ)-induced epileptic behaviors was investigated in rat offspring to address effect of the interaction between morphine and stress. Pregnant rats were divided to four groups of control-saline, control-morphine, stressed-saline and stressed-morphine. In the stressed group, the rats were placed in 25 °C water on 17-19 days of pregnancy. In the morphine/saline group, the rats received morphine/saline on the same days. In the morphine/saline-stressed group, they were exposed to stress and received morphine/saline simultaneously. On postnatal day 15 (P15), blood samples were collected to determine corticosterone (COS) level. On P15 and P25, PTZ was injected to the rest of pups to induce seizure. Then, epileptic behaviors of each rat were individually observed. Latency of tonic-colonic seizures decreased in control-morphine and stressed-saline groups while increasing in stressed-morphine rats compared to control-saline group on P15. Duration of tonic-colonic seizures significantly increased in control-morphine and stressed-saline rats compared to stressed-morphine and control-saline rats on P15, but not P25. COS levels increased in stressed-saline group but decreased in control-morphine group compared to control-saline rats. Body weight was significantly higher in morphine groups than saline treated rats. Prenatal exposure to forced-swim stress potentiated PTZ-induced seizure in the offspring rats. Co-administration of morphine attenuated effect of stress on body weight, COS levels, and epileptic behaviors.

  2. Social isolation in adolescence alters behaviors in the forced swim and sucrose preference tests in female but not in male rats.

    PubMed

    Hong, Suzie; Flashner, Bess; Chiu, Melissa; ver Hoeve, Elizabeth; Luz, Sandra; Bhatnagar, Seema

    2012-01-18

    Social interactions in rodents are rewarding and motivating and social isolation is aversive. Accumulating evidence suggests that disruption of the social environment in adolescence has long-term effects on social interactions, on anxiety-like behavior and on stress reactivity. In previous work we showed that adolescent isolation produced increased reactivity to acute and to repeated stress in female rats, whereas lower corticosterone responses to acute stress and decreased anxiety-related behavior were noted in isolated males. These results indicate a sex specific impact on the effects of social stress in adolescence. However, little is known about whether social isolation impacts behaviors related to affect and whether it does so differently in male and female rats. The present study investigated the impact of adolescent social isolation from day 30-50 of age in male and female Sprague Dawley rats on behavior in the forced swim test at the end of adolescence and in adulthood and on behavior in the sucrose preference test in adulthood. Adult female rats that were isolated in adolescence exhibited increased climbing on the first and second day of the forced swim test and showed an increased preference for sucrose compared to adult females that were group-housed in adolescence. There were no effects in male rats. The results indicate that social isolation in adolescence produces a stable and active behavioral phenotype in adult female rats.

  3. Social isolation in adolescence alters behaviors in the forced swim and sucrose preference tests in female but not in male rats

    PubMed Central

    Hong, Suzie; Flashner, Bess; Chiu, Melissa; Hoeve, Elizabeth ver; Luz, Sandra; Bhatnagar, Seema

    2011-01-01

    Social interactions in rodents are rewarding and motivating and social isolation is aversive. Accumulating evidence suggests that disruption of the social environment in adolescence has long-term effects on social interactions, on anxiety-like behavior and on stress reactivity. In previous work we showed that adolescent isolation produced increased reactivity to acute and to repeated stress in female rats, whereas lower corticosterone responses to acute stress and decreased anxiety-related behavior were noted in isolated males. These results indicate a sex specific impact on the effects of social stress in adolescence. However, little is known about whether social isolation impacts behaviors related to affect and whether it does so differently in male and female rats. The present study investigated the impact of adolescent social isolation from day 30-50 of age in male and female Sprague Dawley rats on behavior in the forced swim test at the end of adolescence and in adulthood and on behavior in the sucrose preference test in adulthood. Adult female rats that were isolated in adolescence exhibited increased climbing on the first and second day of the forced swim test and showed an increased preference for sucrose compared to adult females that were group-housed in adolescence. There were no effects in male rats. The results indicate that social isolation in adolescence produces a stable and active behavioral phenotype in adult female rats. PMID:21907226

  4. Effects of co-administration of fluoxetine or tianeptine with metyrapone on immobility time and plasma corticosterone concentration in rats subjected to the forced swim test.

    PubMed

    Rogóz, Zofia; Skuza, Grazyna; Leśkiewicz, Monika; Budziszewska, Bogusława

    2008-01-01

    Major depression is frequently associated with hyperactivity of the hypothalamic-pituitary-adrenocortical axis, and glucocorticoid synthesis inhibitors have been shown to exert antidepressant action. The aim of the present study was to examine the effect of co-administration of fluoxetine or tianeptine with metyrapone on immobility time and plasma corticosterone concentration in male Wistar rats subjected to the forced swim test. Metyrapone alone (50 mg/kg, but not 25 mg/kg) reduced the immobility time of rats in the forced swim test; moreover, both doses tested (25 and 50 mg/kg), dose-dependently decreased the stress-induced plasma corticosterone concentration. Joint administration of fluoxetine or tianeptine (10 mg/kg) and metyrapone (25 mg/kg - a dose inactive per se) exhibited antidepressant-like activity in the forced swim test in rats. WAY 100636 (a 5-HT(1A) antagonist), but not prazosin (an alpha(1)-adrenergic antagonist), used in doses ineffective in the forced swim test, inhibited the antidepressant-like effect induced by co-administration of fluoxetine or tianeptine with metyrapone (25 mg/kg). Combined treatment of fluoxetine or tianeptine and metyrapone inhibited stress-induced corticosterone secretion to a similar extent as metyrapone alone. The obtained results indicate that metyrapone potentiates the antidepressant-like activity of fluoxetine or tianeptine and that, among other mechanisms, 5-HT(1A) receptors may play some role in this effect. Moreover, metyrapone exerts a beneficial effect on the stress-induced increase in plasma corticosterone concentration. These findings suggest that the co-administration of metyrapone and an antidepressant drug may be useful for the treatment of drug-resistant depression and/or depression associated with a high cortisol level.

  5. Noradrenergic neurotransmission within the bed nucleus of the stria terminalis modulates the retention of immobility in the rat forced swimming test.

    PubMed

    Nagai, Michelly M; Gomes, Felipe V; Crestani, Carlos C; Resstel, Leonardo B M; Joca, Sâmia R L

    2013-06-01

    The bed nucleus of the stria terminalis (BNST) is a limbic structure that has a direct influence on the autonomic, neuroendocrine, and behavioral responses to stress. It was recently reported that reversible inactivation of synaptic transmission within this structure causes antidepressant-like effects, indicating that activation of the BNST during stressful situations would facilitate the development of behavioral changes related to the neurobiology of depression. Moreover, noradrenergic neurotransmission is abundant in the BNST and has an important role in the regulation of emotional processes related to the stress response. Thus, this study aimed to test the hypothesis that activation of adrenoceptors within the BNST facilitates the development of behavioral consequences of stress. To investigate this hypothesis, male Wistar rats were stressed (forced swimming, 15 min) and 24 h later received intra-BNST injections of vehicle, WB4101, RX821002, CGP20712, or ICI118,551, which are selective α(1), α(2), β(1), and β(2) adrenoceptor antagonists, respectively, 10 min before a 5-min forced swimming test. It was observed that administration of WB4101 (10 and 15 nmol), CGP20712 (5 and 10 nmol), or ICI118,551 (5 nmol) into the BNST reduced the immobility time of rats subjected to forced swimming test, indicating an antidepressant-like effect. These findings suggest that activation of α(1), β(1), and β(2) adrenoceptors in the BNST could be involved in the development of the behavioral consequences of stress.

  6. In the rat forced swimming test, NA-system mediated interactions may prevent the 5-HT properties of some subacute antidepressant treatments being expressed.

    PubMed

    Rénéric, Jean-Philippe; Bouvard, Manuel; Stinus, Luis

    2002-04-01

    In the rat forced swimming test (FST), reuptake inhibitors selective of either serotonin (5-HT) or noradrenaline (NA) decrease immobility duration, and increase, respectively, swimming and climbing behaviour. In this study, an almost total 6-OHDA-induced NA-depletion prevented the behavioural effects of desipramine, but not fluoxetine. Interestingly, the serotonin/noradrenaline-reuptake-inhibitor milnacipran, as well as a (desipramine+fluoxetine) combination, could produce both swimming and climbing behaviour in NA-lesioned rats, but not in non-lesioned. The new antidepressant mirtazapine, which enhances both 5-HT and NA transmissions, supposedly through the antagonizing of alpha(2)-adrenoreceptors, dose-dependently reduced immobility and increased climbing behaviour. Interestingly, a (mirtazapine+fluoxetine) combination treatment resulted in additive anti-immobility effects and in the summation of fluoxetine-induced swimming with mirtazapine-induced climbing. Taken together, these data suggest that the NA system mediates presynaptic inhibiting interactions on the 5-HT system, that may involve alpha(2)-receptors, and that may limit the efficacy of mixed serotonin/noradrenaline reuptake inhibition in subacute antidepressant treatments.

  7. Effects of bupropion on the forced swim test and release of dopamine in the nucleus accumbens in ACTH-treated rats.

    PubMed

    Kitamura, Yoshihisa; Yagi, Takahiko; Kitagawa, Kouhei; Shinomiya, Kazuaki; Kawasaki, Hiromu; Asanuma, Masato; Gomita, Yutaka

    2010-08-01

    The dopamine reuptake inhibitor bupropion has clinically been proven to improve depression and treatment-resistant depression. We examined its influence on the duration of immobility during the forced swim test in adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which bupropion acts in this model was explored specifically in relation to the site of action through the use of microinjections into the medial prefrontal cortex and nucleus accumbens. Bupropion significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by D2 and D3 receptor antagonists in normal rats. Furthermore, infusions of bupropion into the nucleus accumbens, but not medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Bupropion treatment plus repeated ACTH treatment significantly increased the extracellular dopamine concentration. These findings suggest the antidepressant-like effect of bupropion to be related to levels of dopamine in the rat nucleus accumbens.

  8. Differential effects of caffeine on the antidepressant-like effect of amitriptyline in female rat subpopulations with low and high immobility in the forced swimming test.

    PubMed

    Enríquez-Castillo, Andrea; Alamilla, Javier; Barral, Jaime; Gourbière, Sébastien; Flores-Serrano, Ana G; Góngora-Alfaro, José L; Pineda, Juan C

    2008-06-01

    The interaction of caffeine (1 mg/kg) and amitriptyline (15 mg/kg) on the immobility time (IT) during Porsolt's forced swimming test (FST) was investigated in female Wistar rats. Akaike's Information Criterion indicated that the ITs recorded from 142 rats during the first day of the FST followed a bimodal distribution. Hence, the median (125.5 s) was used to classify the animals in subpopulations with low (<125.5 s, LI-rats) or high (>125.5 s, HI-rats) immobility. The paired t-test was used to compare the change of ITs between the first and second swimming sessions. Vehicle-treated animals had a significant increase of ITs during the second day of the test, either in LI-rats (77+/-12 s vs. 196+/-8 s, P<0.0001, n=6) or HI-rats (150+/-8 s vs. 201+/-10 s, P<0.02, n=6). In LI-rats amitriptyline only prevented the increase of ITs during the second session (74+/-27 s vs. 97+/-42 s, n=12), whereas in HI-rats the antidepressant produced a significant decrease of ITs during the second session (161+/-22 s vs. 118+/-32 s, n=7, P<0.02). While caffeine alone prevented the increase of ITs in both groups, the methylxanthine abolished the effect of amitriptyline in HI-rats (165+/-23 s vs. 165+/-46 s, n=9), leaving the antidepressant action unaffected in LI-rats (87+/-23 s vs. 96+/-58 s, n=9). These results suggest that the anti-immobility effect of amitriptyline in HI-rats is mediated in part by endogenous adenosine.

  9. 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.

  10. Repeated electroconvulsive stimuli have long-lasting effects on hippocampal BDNF and decrease immobility time in the rat forced swim test.

    PubMed

    Li, Bingjin; Suemaru, Katsuya; Cui, Ranji; Araki, Hiroaki

    2007-03-27

    Electroconvulsive therapy is considered an effective treatment for severe depression. However, the mechanisms for its long-lasting antidepressant efficacy are poorly understood. In the present study, we investigated changes of the immobility time in the forced swim test and brain-derived neurotrophic factor (BDNF) protein after withdrawal from 14-day repeated electroconvulsive stimuli (ECS, 50 mA, 0.2 s) in rats. Immobility time in the forced swim test was markedly decreased 6 h after withdrawal following 14-day ECS treatment. Thereafter, prolongation of the withdrawal period gradually diminished the decreasing effect of immobility time, but significant effects persisted for up to 3 days after the withdrawal. Locomotor activity in the open-field test increased 6 h after withdrawal from the ECS treatment, and the enhanced effect persisted for at least 7 days. The BDNF protein level in the hippocampus was markedly increased 6 h after the withdrawal, and remained high for at least 7 days. These findings provide further evidence that repeated ECS has long-lasting effect on increase in BDNF and locomotor activity and decrease in immobility time in the forced swim test.

  11. Opposite effects of diazepam and beta-CCE on immobility and straw-climbing behavior of rats in a modified forced-swim test.

    PubMed

    Nishimura, H; Ida, Y; Tsuda, A; Tanaka, M

    1989-05-01

    The present study was undertaken to examine how two ligands of the benzodiazepine receptor, which possess anxiolytic or anxiogenic actions, affect both the duration of immobility and the incidence of straw-climbing behavior in rats in a modified forced-swim test. Rats were injected IP with either vehicle, diazepam (0.5, 1, 5 mg/kg), or beta-carboline-3-carboxylic acid ethyl ester (beta-CCE; 0.5, 1, 2, 5 mg/kg), or a combination of diazepam at 1 mg/kg and beta-CCE at 2 mg/kg. In addition, Ro 15-1788 (1 mg/kg), a specific benzodiazepine antagonist, was injected IP 20 min after diazepam injection and immediately after beta-CCE injection, respectively. In the first 5-min period of the forced-swim test, diazepam at 5 mg/kg prolonged the duration of immobility, whereas beta-CCE at 1, 2 and 5 mg/kg reduced its duration. Immediately after the first 5-min test period, 4 straws were suspended above the surface of the water, and the number of straw-climbing attempts and the duration of immobility were measured for a subsequent 5-min test period. Straw-suspension elicited straw-climbing behavior in forced swimming rats, resulting in a shortening of the duration of immobility in this period. All doses of diazepam inhibited straw-climbing attempts and prolonged the duration of immobility in a dose-dependent manner. beta-CCE at 1 or 2 mg/kg enhanced straw-climbing attempts, but did not significantly affect the duration of immobility. Furthermore, the combined administration of diazepam and beta-CCE antagonized the respective drug effects on the duration of immobility and the number of straw-climbing attempts.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Immobility time during the forced swimming test predicts sensitivity to amitriptyline, whereas traveled distance in the circular corridor indicates resistance to treatment in female Wistar rats.

    PubMed

    Flores-Serrano, Ana G; Zaldívar-Rae, Jaime; Salgado, Humberto; Pineda, Juan C

    2015-03-25

    Among the main issues in the pharmacological treatment of depression are the wide variation in response to antidepressants among individual patients and the lack of indexes that allow prediction of which drug will be effective in a particular case. We evaluated whether differential sensitivity to amitriptyline is related to dichotomous categorization of individuals on the basis of their behavioral responses to two common paradigms used to evaluate the potential of tricyclic drugs as antidepressants. Hence, we categorized a cohort of 38 female rats on the basis of their immobility time in the conditioning phase of the forced swimming test [FST; high immobility (HI) vs. low immobility (LI) rats] and their locomotor behavior in the circular corridor test [high locomotor response (HR) vs. low locomotor response (LR) rats]. We subjected the rodents to the FST while under the influence of vehicle (n=20) or amitriptyline (15 mg/kg; n=18). We found no statistical evidence of dependence between categorizations of rats on the basis of their behavior in the FST and circular corridor test. Rats categorized as HI/LI and HR/LR significantly differed in their sensitivity/resistance to amitriptyline, as evidenced by changes (or lack thereof) in their immobility time, climbing time, and swimming time during the FST. These results confirm that different behavioral styles among rats are linked to differential sensitivity/resistance to antidepressants. However, we specifically found that categorizing rats as HI/LI better reflected sensitivity to amitriptyline, whereas categorizing them as HR/LR better revealed resistance to the drug. These differential responses should be considered in experimental approaches. PMID:25646581

  13. Immobility time during the forced swimming test predicts sensitivity to amitriptyline, whereas traveled distance in the circular corridor indicates resistance to treatment in female Wistar rats.

    PubMed

    Flores-Serrano, Ana G; Zaldívar-Rae, Jaime; Salgado, Humberto; Pineda, Juan C

    2015-03-25

    Among the main issues in the pharmacological treatment of depression are the wide variation in response to antidepressants among individual patients and the lack of indexes that allow prediction of which drug will be effective in a particular case. We evaluated whether differential sensitivity to amitriptyline is related to dichotomous categorization of individuals on the basis of their behavioral responses to two common paradigms used to evaluate the potential of tricyclic drugs as antidepressants. Hence, we categorized a cohort of 38 female rats on the basis of their immobility time in the conditioning phase of the forced swimming test [FST; high immobility (HI) vs. low immobility (LI) rats] and their locomotor behavior in the circular corridor test [high locomotor response (HR) vs. low locomotor response (LR) rats]. We subjected the rodents to the FST while under the influence of vehicle (n=20) or amitriptyline (15 mg/kg; n=18). We found no statistical evidence of dependence between categorizations of rats on the basis of their behavior in the FST and circular corridor test. Rats categorized as HI/LI and HR/LR significantly differed in their sensitivity/resistance to amitriptyline, as evidenced by changes (or lack thereof) in their immobility time, climbing time, and swimming time during the FST. These results confirm that different behavioral styles among rats are linked to differential sensitivity/resistance to antidepressants. However, we specifically found that categorizing rats as HI/LI better reflected sensitivity to amitriptyline, whereas categorizing them as HR/LR better revealed resistance to the drug. These differential responses should be considered in experimental approaches.

  14. Effect of the use-dependent, nicotinic receptor antagonist BTMPS in the forced swim test and elevated plus maze after cocaine discontinuation in rats.

    PubMed

    Hall, Brandon J; Pearson, Laura S; Buccafusco, Jerry J

    2010-04-26

    Withdrawal from cocaine use often is associated with anxiety and depressive states. In this study the use-dependent, nicotinic acetylcholine receptor antagonist bis-(2,2,6,6-tetramethyl-4-piperidinyl) sebacate (BTMPS) was studied for its ability to reduce these symptoms in two rat models of anxiety and depression. Rats were administered saline vehicle, or two escalating doses of cocaine, for a period of 5 days and they were evaluated during the period after cocaine discontinuation in the elevated plus maze (anxiety) and the forced swim test (affect). BTMPS (0.25, 0.5, or 0.75mg/kg) was co-administered with saline or cocaine in the dependence phase. Withdrawal from cocaine administration alone resulted in reductions in both the time spent in the open arms of the elevated plus maze test, as well as entries into, and out of, the open arms of the maze. Withdrawal from cocaine also resulted in a reduction of escape behaviors, and the time to first immobility, in the forced swim test. Treatment with BTMPS produced a reversal of cocaine-induced anxiety-like behaviors in the elevated plus maze, including an increase (up to 68%) in time spent in the open arms of the maze and an increase in the number of crossings between open and enclosed arms. BTMPS also reduced depressive-like behaviors associated with the forced swim test, including up to a 62% increase in the time to first immobility and a 50% increase in escape behavior. These results provide proof of concept for the development and use of cholinergic compounds in the treatment of substance abuse. PMID:20226229

  15. Effect of the use-dependent, nicotinic receptor antagonist BTMPS in the forced swim test and elevated plus maze after cocaine discontinuation in rats.

    PubMed

    Hall, Brandon J; Pearson, Laura S; Buccafusco, Jerry J

    2010-04-26

    Withdrawal from cocaine use often is associated with anxiety and depressive states. In this study the use-dependent, nicotinic acetylcholine receptor antagonist bis-(2,2,6,6-tetramethyl-4-piperidinyl) sebacate (BTMPS) was studied for its ability to reduce these symptoms in two rat models of anxiety and depression. Rats were administered saline vehicle, or two escalating doses of cocaine, for a period of 5 days and they were evaluated during the period after cocaine discontinuation in the elevated plus maze (anxiety) and the forced swim test (affect). BTMPS (0.25, 0.5, or 0.75mg/kg) was co-administered with saline or cocaine in the dependence phase. Withdrawal from cocaine administration alone resulted in reductions in both the time spent in the open arms of the elevated plus maze test, as well as entries into, and out of, the open arms of the maze. Withdrawal from cocaine also resulted in a reduction of escape behaviors, and the time to first immobility, in the forced swim test. Treatment with BTMPS produced a reversal of cocaine-induced anxiety-like behaviors in the elevated plus maze, including an increase (up to 68%) in time spent in the open arms of the maze and an increase in the number of crossings between open and enclosed arms. BTMPS also reduced depressive-like behaviors associated with the forced swim test, including up to a 62% increase in the time to first immobility and a 50% increase in escape behavior. These results provide proof of concept for the development and use of cholinergic compounds in the treatment of substance abuse.

  16. The selective glucocorticoid receptor antagonist ORG 34116 decreases immobility time in the forced swim test and affects cAMP-responsive element-binding protein phosphorylation in rat brain.

    PubMed

    Bachmann, Cornelius G; Bilang-Bleuel, Alicia; De Carli, Sonja; Linthorst, Astrid C E; Reul, Johannes M H M

    2005-01-01

    Glucocorticoid receptor (GR) antagonists can block the retention of the immobility response in the forced swimming test. Recently, we showed that forced swimming evokes a distinct spatiotemporal pattern of cAMP-responsive element-binding protein (CREB) phosphorylation in the dentate gyrus (DG) and neocortex. In the present study, we found that chronic treatment of rats with the selective GR antagonist ORG 34116 decreased the immobility time in the forced swim test, increased baseline levels of phosphorylated CREB (P-CREB) in the DG and neocortex and affected the forced swimming-induced changes in P-CREB levels in a time- and site-specific manner. Overall, we observed that, in control rats, forced swimming evoked increases in P-CREB levels in the DG and neocortex, whereas in ORG 34116-treated animals a major dephosphorylation of P-CREB was observed. These observations underscore an important role of GRs in the control of the phosphorylation state of CREB which seems to be of significance for the immobility response in the forced swim test and extend the molecular mechanism of action of GRs in the brain.

  17. Effects of imipramine or GABA(B) receptor ligands on the immobility, swimming and climbing in the forced swim test in rats following discontinuation of cocaine self-administration.

    PubMed

    Frankowska, Małgorzata; Gołda, Anna; Wydra, Karolina; Gruca, Piotr; Papp, Mariusz; Filip, Małgorzata

    2010-02-10

    We tested if discontinuation of cocaine self-administration can lead to the development of depressive-like symptoms in the forced swim test expressed as changes in immobility, swimming and climbing behaviors in rats. A "yoked" procedure in which rats were run simultaneously in groups of three, with two rats received the passive injection of cocaine or saline, was employed. Later, we examined whether acute treatment with the classical antidepressant imipramine or GABA(B) receptor ligands could alter the increases in immobility recorded after discontinuation of self-administered cocaine. We found a significant increase (44%) in the immobility time 3 days following discontinuation of cocaine (0.5mg/kg/infusion/2h daily) self-administration for 14 days; such enhancement resembled that observed in rats following the chronic mild stress. Acute administration with imipramine (15 or 30 mg/kg), the GABA(B) receptor agonists baclofen (0.125 mg/kg) and SKF 97541 (0.005 mg/kg), the positive allosteric modulator CGP 7930 (0.3mg/kg) or the antagonist SCH 50911 (0.3mg/kg) counteracted the cocaine discontinuation-induced enhancement in the immobility time. The enhanced immobility time in rats that self-administered cocaine (but not given cocaine passively) may reflect the motivated or cognitive processes of reinforced responding of cocaine and could be a potential driver of the addiction process per se. Moreover, either blockade or stimulation of GABA(B) receptors by their ligands in very low doses attenuated the enhanced immobility time in rats after discontinuation of cocaine self-administration and these findings extend preclinical studies demonstrating the potential involvement of GABA(B) receptor ligands to reduce cocaine craving.

  18. Ozone modulates the effects of imipramine on immobility in the forced swim test, and nonspecific parameters of hippocampal oxidative stress in the rat.

    PubMed

    Mokoena, Mmalebuso L; Harvey, Brian H; Oliver, Douglas W; Brink, Christiaan B

    2010-06-01

    Depression has been associated with oxidative stress. There is increased awareness of the role of environmental toxins in the development of mood disorders. Ozone, a pro-oxidant and environmental pollutant, has been noted to have central nervous system effects. We investigated the effects of acute and chronic ozone inhalation on the response of imipramine in the forced-swim test (FST) and on biomarkers of oxidative stress in rat hippocampus. Sprague Dawley rats were exposed to 0, 0.25 or 0.7 ppm ozone per inhalation 4 h daily for either 30 days (chronic) or once (acute). Animals were then injected intraperitoneally with imipramine (10 mg/kg) or saline 24, 5 and 1 h before the forced-swim test. Hippocampal superoxide accumulation and lipid peroxidation were measured. Imipramine evoked an antidepressant-like effect independent of acute or chronic ozone exposure. However, 0.7 ppm acute ozone and 0.25 ppm chronic ozone attenuated the antidepressant-like effects of imipramine. The ozone exposures also elevated hippocampal superoxide accumulation and lipid peroxidation. Importantly, imipramine reversed the lipid peroxidation induced by chronic ozone, thereby preventing cellular damage induced by oxidative stress. Ozone exposure presents a feasible model with etiological validity to investigate oxidative stress in depression and antidepressant action.

  19. Antidepressant-like effects of the ethyl acetate soluble fraction of the root bark of Morus alba on the immobility behavior of rats in the forced swim test.

    PubMed

    Lim, Dong Wook; Kim, Yun Tai; Park, Ji-Hae; Baek, Nam-In; Han, Daeseok

    2014-06-12

    In this study, the antidepressant-like effects of Morus alba fractions in rats were investigated in the forced swim test (FST). Male Wistar rats (9-week-old) were administered orally the M. alba ethyl acetate (EtOAc 30 and 100 mg/kg) and M. alba n-butanol fractions (n-BuOH 30 and 100 mg/kg) every day for 7 consecutive days. On day 7, 1 h after the final administration of the fractions, the rats were exposed to the FST. M. alba EtOAc fraction at the dose of 100 mg/kg induced a decrease in immobility behavior (p < 0.01) with a concomitant increase in both climbing (p < 0.05) and swimming (p < 0.05) behaviors when compared with the control group, and M. alba EtOAc fraction at the dose of 100 mg/kg decreased the hypothalamic-pituitary-adrenal (HPA) axis response to the stress, as indicated by an attenuated corticosterone response and decreased c-fos immunoreactivity in the hippocampal and hypothalamic paraventricular nucleus (PVN) region. These findings demonstrated that M. alba EtOAc fraction have beneficial effects on depressive behaviors and restore both altered c-fos expression and HPA activity.

  20. Diet influences cocaine withdrawal behaviors in the forced swimming test.

    PubMed

    Loebens, M; Barros, H M T

    2003-01-01

    The effects of drugs of abuse might depend on several environmental factors, among them the individual's feeding habits. It was our objective to study the influence of the diet on cocaine acute behavioral effects and during the first 5 days of withdrawal after prolonged treatment. Rats were fed a balanced diet, high-protein diet, high-carbohydrate diet or high-fat diet from weaning to adulthood. Adult rats were injected with 15 mg/kg cocaine 24, 5 and 1 h before the forced swimming retest or the drug was administered daily during 15 days and the animals were evaluated in the forced swimming test on five daily occasions after drug withdrawal. Diets alone did not induce significant behavioral differences in locomotion, immobility, swimming, climbing or head shakes. Acute cocaine reduced immobility during the forced swimming test and increased locomotion demonstrating a nonspecific antiimmobility effect related to hyperactivity. Acute cocaine reduced head shakes of rats fed high-protein and high-carbohydrate diets. After cocaine withdrawal, head shakes were decreased for rats fed any of the diets and rats were more immobile if fed a high-fat diet and were less immobile if fed a high-protein or high-carbohydrate diet. In conclusion, differences in the amounts of macronutrients in the diet may cause different behavioral outcomes after acute cocaine and during cocaine withdrawal.

  1. Cerebral metabolic changes in a depression-like rat model of chronic forced swimming studied by ex vivo high resolution 1H magnetic resonance spectroscopy.

    PubMed

    Li, Chun-Xia; Wang, Yaqiang; Gao, Hongchang; Pan, Wen-Ju; Xiang, Yun; Huang, Mingming; Lei, Hao

    2008-11-01

    Many previous in vivo (1)H magnetic resonance spectroscopy (MRS) studies have shown that patients with major depressive disorder (MDD) are associated with perturbations of cerebral metabolism of neurotransmitters glutamate (Glu) and gamma-aminobutyric acid (GABA). In this study, we investigated the changes of cerebral metabolism in a depression-like rat model of chronic forced swimming stress (CFSS). The aims are to further understand the pathophysiological mechanisms underlying CFSS treatment, and to further establish the face and predictive validity of the CFSS model. The results showed that, relative to control, the CFSS rats had significantly reduced Glu, taurine and glutamate + glutamine (Glx) levels in the PFC, and significantly reduced N-acetyl aspartate (NAA) level, Glu level and Glu/GABA ratio in the hippocampus. Taking together, these results suggest that CFSS treatment can induce region-specific changes in the metabolism of Glu. The CFSS model might be used to study antidepressants specifically targeting the central glutamatergic system. PMID:18473166

  2. Effects of (+)-8-OH-DPAT on the duration of immobility during the forced swim test and hippocampal cell proliferation in ACTH-treated rats.

    PubMed

    Miyake, Ayaka; Kitamura, Yoshihisa; Miyazaki, Ikuko; Asanuma, Masato; Sendo, Toshiaki

    2014-07-01

    In the present study, we examined the effect of ACTH on the immobilization of rats in the forced swim test and hippocampal cell proliferation after administration of the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-di-n-propylamino tetralin ((+)-8-OH-DPAT). Chronic treatment with (+)-8-OH-DPAT (0.01-0.1 mg/kg, s.c.) significantly decreased the duration of immobility in saline- and ACTH-treated rats. Chronic administration of ACTH caused a significant decrease in hippocampal cell proliferation. However, (+)-8-OH-DPAT significantly normalized cell proliferation in ACTH-treated rats. We then investigated the effects of (+)-8-OH-DPAT on the expression of brain-derived neurotrophic factor (BDNF) and cyclin D1 (elements of cyclic adenosine monophosphate response element-binding protein (CREB)-BDNF and Wnt signaling pathways, respectively) in the hippocampus of saline- and ACTH-treated rats. ACTH treatment significantly decreased the expression of cyclin D1, while treatment with (+)-8-OH-DPAT normalized the expression of cyclin D1 in ACTH-treated rats. However, the expression of BDNF did not change in either saline- or ACTH-treated rats. These findings suggest that the antidepressant effects of (+)-8-OH-DPAT in treatment-resistant animals may be attributed to an enhancement of hippocampal cell proliferation, at least in part due to an enhancement of cyclin D1 expression.

  3. A2 noradrenergic neurons regulate forced swim test immobility.

    PubMed

    Nam, Hyungwoo; Kerman, Ilan A

    2016-10-15

    The Wistar-Kyoto (WKY) rat is a widely used animal model of depression, which is characterized by dysregulation of noradrenergic signaling. We previously demonstrated that WKY rats show a unique behavioral profile on the forced swim test (FST), characterized by high levels of immobility upon initial exposure and a greater learning-like response by further increasing immobility upon re-exposure than the genetically related Wistar rats. In the current study we aimed to determine whether altered activation of brainstem noradrenergic cell groups contributes to this behavioral profile. We exposed WKY and Wistar rats, to either 5min of forced swim or to the standard two-day FST (i.e. 15min forced swim on Day 1, followed by 5min on Day 2). We then stained their brains for FOS/tyrosine hydroxylase double-immunocytochemistry to determine potential differences in the activation of the brainstem noradrenergic cell groups. We detected a relative hyperactivation in the locus coeruleus of WKY rats when compared to Wistars in response to both one- and two-day forced swim. In contrast, within the A2 noradrenergic cell group, WKY rats exhibited diminished levels of FOS across both days of the FST, suggesting their lesser activation. We followed up these observations by selectively lesioning the A2 neurons, using anti-dopamine-β-hydroxylase-conjugated saporin, in Wistar rats, which resulted in increased FST immobility on both days of the test. Together these data indicate that the A2 noradrenergic cell group regulates FST behavior, and that its hypoactivation may contribute to the unique behavioral phenotype of WKY rats.

  4. Effects of a glycine transporter-1 inhibitor and D-serine on MK-801-induced immobility in the forced swimming test in rats.

    PubMed

    Kawaura, Kazuaki; Koike, Hiroyuki; Kinoshita, Kohnosuke; Kambe, Daiji; Kaku, Ayaka; Karasawa, Jun-ichi; Chaki, Shigeyuki; Hikichi, Hirohiko

    2015-02-01

    Glutamatergic dysfunction, particularly the hypofunction of N-methyl-D-aspartate (NMDA) receptors, is involved in the pathophysiology of schizophrenia. The positive modulation of the glycine site on the NMDA receptor has been proposed as a novel therapeutic approach for schizophrenia. However, its efficacy against negative symptoms, which are poorly managed by current medications, has not been fully addressed. In the present study, the effects of the positive modulation of the glycine site on the NMDA receptor were investigated in an animal model of negative symptoms of schizophrenia. The subchronic administration of MK-801 increased immobility in the forced swimming test in rats without affecting spontaneous locomotor activity. The increased immobility induced by MK-801 was attenuated by the atypical antipsychotic clozapine but not by either the typical antipsychotic haloperidol or the antidepressant imipramine, indicating that the increased immobility induced by subchronic treatment with MK-801 in the forced swimming test may represent a negative symptom of schizophrenia. Likewise, positive modulation of the glycine sites on the NMDA receptor using an agonist for the glycine site, D-serine, and a glycine transporter-1 inhibitor, N-[(3R)-3-([1,1'-biphenyl]-4-yloxy)-3-(4-fluorophenyl)propyl]-N-methylglycine hydrochloride (NFPS), significantly reversed the increase in immobility in MK-801-treated rats without reducing the immobility time in vehicle-treated rats. The present results show that the stimulation of the NMDA receptor through the glycine site on the receptor either directly with D-serine or by blocking glycine transporter-1 attenuates the immobility elicited by the subchronic administration of MK-801 and may be potentially useful for the treatment of negative symptoms of schizophrenia.

  5. Forced swim test: What about females?

    PubMed

    Kokras, Nikolaos; Antoniou, Katerina; Mikail, Hudu G; Kafetzopoulos, Vasilios; Papadopoulou-Daifoti, Zeta; Dalla, Christina

    2015-12-01

    In preclinical studies screening for novel antidepressants, male and female animals should be used. However, in a widely used antidepressant test, the forced swim test (FST), sex differences between males and females are not consistent. These discrepancies may discourage the inclusion of females in FST studies. In order to overcome this problem and provide a detailed insight regarding the use of female animals in the FST, we designed the following experiment and we performed a thorough analysis of the relevant literature. Male and female Wistar adult rats were subjected to the FST and sertraline was used as an antidepressant in two doses (10 mg/kg and 40 mg/kg, 3 injections in 24 h). Rodents were subjected in the two FST sessions during all possible combinations of the estrous cycle stages. We found that females exhibited higher levels of immobility than males and this sex difference was alleviated following antidepressant treatment. Sertraline at both doses enhanced swimming in both sexes, but females appeared more responsive to lower sertraline doses regarding immobility levels. Surprisingly, the high sertraline dose enhanced climbing particularly in proestrous and diestrous. Marked sex differences were also observed in the frequency of head swinging, with females exhibiting lower counts than males. Conclusively, when screening for new antidepressants, it is recommended to use standard FST procedures and if possible to include females in all phases of the cycle. Using only one dose of an investigational drug in females in certain phases of the cycle could result to false negative results.

  6. Water spray-induced grooming is negatively correlated with depressive behavior in the forced swimming test in rats.

    PubMed

    Shiota, Noboru; Narikiyo, Kimiya; Masuda, Akira; Aou, Shuji

    2016-05-01

    Rodents show grooming, a typical self-care behavior, under stress and non-stress conditions. Previous studies revealed that grooming under stress conditions such as the open-field test (OFT) or the elevated plus-maze test (EPM) is associated with anxiety, but the roles of grooming under non-stress conditions are not well understood. Here, we examined spray-induced grooming as a model of grooming under a non-stress condition to investigate the relationship between this grooming and depression-like behavior in the forced swim test (FST) and tail suspension test, and we compared spray-induced grooming with OFT- and EPM-induced grooming. The main finding was that the duration of spray-induced grooming, but not that of OFT/EPM-induced grooming, was negatively correlated with the duration of immobility in the FST, an index of depression-like behavior. The results suggest that spray-induced grooming is functionally different from the grooming in the OFT and EPM and is related to reduction of depressive behavior.

  7. The Post-Ovariectomy Interval Affects the Antidepressant-Like Action of Citalopram Combined with Ethynyl-Estradiol in the Forced Swim Test in Middle Aged Rats.

    PubMed

    Vega Rivera, Nelly M; Gallardo Tenorio, Alfredo; Fernández-Guasti, Alonso; Estrada Camarena, Erika

    2016-01-01

    The use of a combined therapy with low doses of estrogens plus antidepressants to treat depression associated to perimenopause could be advantageous. However the use of these combinations is controversial due to several factors, including the time of intervention in relation to menopause onset. This paper analyzes whether time post-OVX influences the antidepressant-like action of a combination of ethynyl-estradiol (EE₂) and citalopram (CIT) in the forced swim test (FST). Middle-aged (15 months old) female Wistar rats were ovariectomized and after one or three weeks treated with EE₂ (1.25, 2.5 or 5.0 µg/rat, s.c.; -48 h) or CIT (1.25, 2.5, 5.0 or 10 mg/kg, i.p./3 injections in 24 h) and tested in the FST. In a second experiment, after one or three weeks of OVX, rats received a combination of an ineffective dose of EE₂ (1.25 µg/rat, s.c., -48 h) plus CIT (2.5 mg/kg, i.p./3 injections in 24 h) and subjected to the FST. Finally, the uteri were removed and weighted to obtain an index of the peripheral effects of EE₂ administration. EE₂ (2.5 or 5.0 µg/rat) reduced immobility after one but not three weeks of OVX. In contrast, no CIT dose reduced immobility at one or three weeks after OVX. When EE₂ (1.25 µg/rat) was combined with CIT (2.5 mg/kg) an antidepressant-like effect was observed at one but not three weeks post-OVX. The weight of the uteri augmented when EE₂ was administrated three weeks after OVX. The data suggest that the time post-OVX is a crucial factor that contributes to observe the antidepressant-like effect of EE₂ alone or in combination with CIT. PMID:27153072

  8. The Post-Ovariectomy Interval Affects the Antidepressant-Like Action of Citalopram Combined with Ethynyl-Estradiol in the Forced Swim Test in Middle Aged Rats.

    PubMed

    Vega Rivera, Nelly M; Gallardo Tenorio, Alfredo; Fernández-Guasti, Alonso; Estrada Camarena, Erika

    2016-05-03

    The use of a combined therapy with low doses of estrogens plus antidepressants to treat depression associated to perimenopause could be advantageous. However the use of these combinations is controversial due to several factors, including the time of intervention in relation to menopause onset. This paper analyzes whether time post-OVX influences the antidepressant-like action of a combination of ethynyl-estradiol (EE₂) and citalopram (CIT) in the forced swim test (FST). Middle-aged (15 months old) female Wistar rats were ovariectomized and after one or three weeks treated with EE₂ (1.25, 2.5 or 5.0 µg/rat, s.c.; -48 h) or CIT (1.25, 2.5, 5.0 or 10 mg/kg, i.p./3 injections in 24 h) and tested in the FST. In a second experiment, after one or three weeks of OVX, rats received a combination of an ineffective dose of EE₂ (1.25 µg/rat, s.c., -48 h) plus CIT (2.5 mg/kg, i.p./3 injections in 24 h) and subjected to the FST. Finally, the uteri were removed and weighted to obtain an index of the peripheral effects of EE₂ administration. EE₂ (2.5 or 5.0 µg/rat) reduced immobility after one but not three weeks of OVX. In contrast, no CIT dose reduced immobility at one or three weeks after OVX. When EE₂ (1.25 µg/rat) was combined with CIT (2.5 mg/kg) an antidepressant-like effect was observed at one but not three weeks post-OVX. The weight of the uteri augmented when EE₂ was administrated three weeks after OVX. The data suggest that the time post-OVX is a crucial factor that contributes to observe the antidepressant-like effect of EE₂ alone or in combination with CIT.

  9. Effects of prolonged ethanol vapor exposure on forced swim behavior, and neuropeptide Y and corticotropin-releasing factor levels in rat brains.

    PubMed

    Walker, Brendan M; Drimmer, David A; Walker, Jennifer L; Liu, Tianmin; Mathé, Aleksander A; Ehlers, Cindy L

    2010-09-01

    Depressive symptoms in alcohol-dependent individuals are well-recognized and clinically relevant phenomena. The etiology has not been elucidated although it is clear that the depressive symptoms may be alcohol independent or alcohol induced. To contribute to the understanding of the neurobiology of chronic ethanol use, we investigated the effects of chronic intermittent ethanol vapor exposure on behaviors in the forced swim test (FST) and neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) levels in specific brain regions. Adult male Wistar rats were subjected to intermittent ethanol vapor (14 h on/10 h off) or air exposure for 2 weeks and were then tested at three time points corresponding to acute withdrawal (8-12 h into withdrawal) and protracted withdrawal (30 and 60 days of withdrawal) in the FST. The behaviors that were measured in the five-min FST consisted of latency to immobility, swim time, immobility time, and climbing time. The FST results showed that the vapor-exposed animals displayed depressive-like behaviors; for instance, decreased latency to immobility in acute withdrawal and decreased latency to immobility, decreased swim time and increased immobility time in protracted withdrawal, with differences between air- and vapor-exposed animals becoming more pronounced over the 60-day withdrawal period. NPY levels in the frontal cortex of the vapor-exposed animals were decreased compared with the control animals, and CRF levels in the amygdala were correlated with increased immobility time. Thus, extended ethanol vapor exposure produced long-lasting changes in FST behavior and NPY levels in the brain. PMID:20705420

  10. Effects of prolonged ethanol vapor exposure on forced swim behavior, and neuropeptide Y and corticotropin-releasing factor levels in rat brains.

    PubMed

    Walker, Brendan M; Drimmer, David A; Walker, Jennifer L; Liu, Tianmin; Mathé, Aleksander A; Ehlers, Cindy L

    2010-09-01

    Depressive symptoms in alcohol-dependent individuals are well-recognized and clinically relevant phenomena. The etiology has not been elucidated although it is clear that the depressive symptoms may be alcohol independent or alcohol induced. To contribute to the understanding of the neurobiology of chronic ethanol use, we investigated the effects of chronic intermittent ethanol vapor exposure on behaviors in the forced swim test (FST) and neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) levels in specific brain regions. Adult male Wistar rats were subjected to intermittent ethanol vapor (14 h on/10 h off) or air exposure for 2 weeks and were then tested at three time points corresponding to acute withdrawal (8-12 h into withdrawal) and protracted withdrawal (30 and 60 days of withdrawal) in the FST. The behaviors that were measured in the five-min FST consisted of latency to immobility, swim time, immobility time, and climbing time. The FST results showed that the vapor-exposed animals displayed depressive-like behaviors; for instance, decreased latency to immobility in acute withdrawal and decreased latency to immobility, decreased swim time and increased immobility time in protracted withdrawal, with differences between air- and vapor-exposed animals becoming more pronounced over the 60-day withdrawal period. NPY levels in the frontal cortex of the vapor-exposed animals were decreased compared with the control animals, and CRF levels in the amygdala were correlated with increased immobility time. Thus, extended ethanol vapor exposure produced long-lasting changes in FST behavior and NPY levels in the brain.

  11. Intra-lateral septal infusions of folic acid alone or combined with various antidepressant drugs produce antidepressant-like actions in male Wistar rats forced to swim.

    PubMed

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

    2012-01-10

    Intra-cerebral administrations of folic acid produce antidepressant-like effects; either alone or combined with several antidepressant drugs. However, the specific limbic structures implied in the antidepressant-like actions of folic acid are un-known. Thus, intra-lateral septal infusions of folic acid (5.0 nmol, P<0.05; 10.0 nmol, P<0.05) or oral administrations of folic acid (50 mg/kg, P<0.05, p.o.; 75.0; mg/kg, P<0.05, p.o.) or systemic administrations of fluoxetine (20.0 mg/kg, P<0.05; 25.0 mg/kg, P<0.05) reduced immobility by increasing swimming behavior in the forced swimming test (FST) of male Wistar rats. Conversely, desipramine (10.0 mg/kg, P<0.05; 15.0 mg/kg, P<0.05) reduced immobility by increasing climbing behavior. Subthreshold doses of folic acid (2.5 nmol/intra-LSN) combined with subthreshold doses of folic acid (25.0 mg/kg, p.o., P<0.05) or with subthreshold doses of fluoxetine (15.0 mg/kg, P<0.05) and they produced antidepressant-like effects which were canceled by ketanserin. In conclusion, intra-lateral septal infusions of folic acid alone or combined with systemic doses of folic acid or fluoxetine reduced immobility in the FST. These antidepressant-like actions, probably, were due to modifications of the serotonergic system since swimming behavior was increased and these effects were canceled by ketanserin.

  12. Effects of Prolonged Ethanol Vapor Exposure on Forced Swim Behavior, and Neuropeptide Y and Corticotropin Releasing Factor Levels in Rat Brains

    PubMed Central

    Walker, Brendan M.; Drimmer, David A.; Walker, Jennifer L.; Liu, Tianmin; Mathé, Aleksander A.; Ehlers, Cindy L.

    2010-01-01

    Depressive symptoms in alcohol-dependent individuals are well recognized and clinically relevant phenomena. The etiology has not been elucidated although it is clear that the depressive symptoms may be alcohol independent or alcohol-induced. In order to contribute to the understanding of the neurobiology of chronic ethanol use, we investigated the effects of chronic intermittent ethanol vapor exposure on behaviors in the forced swim test (FST) and neuropeptide Y (NPY) and corticotropin releasing factor (CRF) levels in specific brain regions. Adult male Wistar rats were subjected to intermittent ethanol vapor (14 hours on / 10 hours off) or air exposure for two weeks and were then tested at three time points corresponding to acute withdrawal (8–12 hours into withdrawal) and protracted withdrawal (30 and 60 days of withdrawal) in the FST. The behaviors that were measured in the five minute FST consisted of latency to immobility, swim time, immobility time and climbing time. The FST results showed that the vapor-exposed animals displayed depressive-like behaviors, for instance decreased latency to immobility in acute withdrawal and decreased latency to immobility, decreased swim time and increased immobility time in protracted withdrawal, with differences between air- and vapor-exposed animals becoming more pronounced over the 60 day withdrawal period. NPY levels in the frontal cortex of the vapor-exposed animals were decreased compared to the control animals and CRF levels in the amygdala were correlated with increased immobility time. Thus, extended ethanol vapor exposure produced long-lasting changes in FST behavior and NPY levels in the brain. PMID:20705420

  13. Omega-3 fatty acid deficiency does not alter the effects of chronic fluoxetine treatment on central serotonin turnover or behavior in the forced swim test in female rats.

    PubMed

    McNamara, Robert K; Able, Jessica A; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Lipton, Jack W

    2013-12-01

    While translational evidence suggests that long-chain omega-3 fatty acid status is positively associated with the efficacy of selective serotonin reuptake inhibitor drugs, the neurochemical mechanisms mediating this interaction are not known. Here, we investigated the effects of dietary omega-3 (n-3) fatty acid insufficiency on the neurochemical and behavioral effects of chronic fluoxetine (FLX) treatment. Female rats were fed diets with (CON, n=56) or without (DEF, n=40) the n-3 fatty acids during peri-adolescent development (P21-P90), and one half of each group was administered FLX (10mg/kg/day) for 30days (P60-P90) prior to testing. In adulthood (P90), regional brain serotonin (5-HT) and 5-hydroxyindoleacetic (5-HIAA) concentrations, presynaptic markers of 5-HT neurotransmission, behavioral responses in the forced swim test (FST), and plasma FLX and norfluoxetine (NFLX) concentrations were investigated. Peri-adolescent n-3 insufficiency led to significant reductions in cortical docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (-25%, p≤0.0001) and DEF+FLX (-28%, p≤0.0001) rats. Untreated DEF rats exhibited significantly lower regional 5-HIAA/5-HT ratios compared with untreated CON rats, but exhibited similar behavioral responses in the FST. In both CON and DEF rats, chronic FLX treatment similarly and significantly decreased 5-HIAA concentrations and the 5-HIAA/5-HT ratio in the hypothalamus, hippocampus, and nucleus accumbens, brainstem tryptophan hydroxylase-2 mRNA expression, and immobility in the FST. While the FLX-induced reduction in 5-HIAA concentrations in the prefrontal cortex was significantly blunted in DEF rats, the reduction in the 5-HIAA/5-HT ratio was similar to CON rats. Although plasma FLX and NFLX levels were not significantly different in DEF and CON rats, the NFLX/FLX ratio was significantly lower in DEF+FLX rats. These preclinical data demonstrate that n-3 fatty acid deficiency does not significantly reduce the effects of chronic

  14. Omega-3 Fatty Acid Deficiency Does Not Alter the Effects of Chronic Fluoxetine Treatment on Central Serotonin Turnover or Behavior in the Forced Swim Test in Female Rats

    PubMed Central

    McNamara, Robert K.; Able, Jessica A.; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Lipton, Jack W.

    2013-01-01

    While translational evidence suggests that long-chain omega-3 fatty acid status is positively associated with the efficacy of selective serotonin reuptake inhibitor drugs, the neurochemical mechanisms mediating this interaction are not known. Here we investigated the effects of dietary omega-3 (n-3) fatty acid insufficiency on the neurochemical and behavioral effects of chronic fluoxetine (FLX) treatment. Female rats were fed diets with (CON, n=56) or without (DEF, n=40) the n-3 fatty acids during peri-adolescent development (P21-P90), and one half of each group were administered FLX (10 mg/kg/d) for 30 d (P60-P90) prior to testing. In adulthood (P90), regional brain serotonin (5-HT) and 5-hydroxyindoleacetic (5-HIAA) concentrations, presynaptic markers of 5-HT neurotransmission, behavioral responses in the forced swim test (FST), and plasma FLX and norfluoxetine (NFLX) concentrations were investigated. Peri-adolescent n-3 insufficiency led to significant reductions in cortical docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (−25%, p≤0.0001) and DEF+FLX (−28%, p≤0.0001) rats. Untreated DEF rats exhibited significantly lower regional 5-HIAA/5-HT ratios compared with untreated CON rats, but exhibited similar behavioral responses in the FST. In both CON and DEF rats, chronic FLX treatment similarly and significantly decreased 5-HIAA concentrations and the 5-HIAA/5-HT ratio in the hypothalamus, hippocampus, and nucleus accumbens, brainstem tryptophan hydroxylase-2 mRNA expression, and immobility in the FST. While the FLX-induced reduction in 5-HIAA concentrations in the prefrontal cortex was significantly blunted in DEF rats, the reduction in the 5-HIAA/5-HT ratio was similar to CON rats. Although plasma FLX and NFLX levels were not significantly different in DEF and CON rats, the NFLX/FLX ratio was significantly lower in DEF+FLX rats. These preclinical data demonstrate that n-3 fatty acid deficiency does not significantly reduce the effects of chronic

  15. Age-related changes in the antidepressant-like effect of desipramine and fluoxetine in the rat forced-swim test.

    PubMed

    Olivares-Nazario, Maribel; Fernández-Guasti, Alonso; Martínez-Mota, Lucía

    2016-02-01

    Some reports suggest that older patients are less responsive to antidepressants than young adults, but this idea has not been fully supported. Here, we investigated the role of aging in the behavioral effects of the antidepressants, desipramine (DMI) (5, 10, and 20 mg/kg) and fluoxetine (FLX) (5, 10, and 20 mg/kg) in young adults (3-5 months), middle-aged (MA, 12-15 months), and senescent (SE, 23-25 months) male rats in the forced-swim test. In addition, locomotor activity and motor coordination were assessed as side-effects. DMI and fluoxetine produced an antidepressant-like effect in YA and MA animals, although in the latter group, a shift to the right in the dose-response curve was found for DMI. Importantly, neither drug was effective in SE animals. Motor side-effects were produced mainly by DMI in MA and SE rats. Therefore, a decrease in the antidepressant-like effect is associated strongly with senescence as well as an increased vulnerability to motor side-effects, particularly of tricyclics. This study is significant because SE animals are scarcely studied in pharmacological screening tests, and our findings might be useful for improving antidepressant treatments for the increasing aged population.

  16. Facilitating antidepressant-like actions of estrogens are mediated by 5-HT1A and estrogen receptors in the rat forced swimming test.

    PubMed

    Estrada-Camarena, E; López-Rubalcava, C; Fernández-Guasti, A

    2006-09-01

    Previous studies have shown that 17beta-estradiol (E2) induces antidepressant-like actions per se and potentiates those produced by fluoxetine (FLX) in the forced swimming test (FST). The aim of the present work was to explore the participation of serotonin 1A receptors (5-HT1A) and estrogen receptors (ERs) in the antidepressant-like actions of E2, FLX or their combination in the FST. Although all antidepressants reduce behavioral immobility, antidepressants that modulate serotonergic neurotransmission increase swimming behavior whereas those that modulate the catecholaminergic neurotransmission increase climbing behavior. Thus, using this animal model, it is possible to infer which neurotransmitter system is modulating the action of an antidepressant compound. Ovariectomized female Wistar rats were used in all experiments. In the first experiment, an effective dose of E2 (10 microg/rat, -48 h) was combined with several doses (0.5, 1.0 and 2 mg/kg) of RU 58668 (a pure ER antagonist) 48 h previous to the FST. The second experiment evaluated the action of (1 mg/kg, -48 h or -23, -5 and -1 h) WAY 100635 (5-HT1A receptor antagonist) on the antidepressant-like action of FLX (10 mg/kg, -23, -5 and -1 h). In the third experiment, the effect of RU 58668 (2 mg/kg, -48) or WAY 100635 (1 mg/kg, -48 h) on the antidepressant-like action of the combination of a sub-optimal dose of E2 (2.5 microg/rat, -48 h) plus a non-effective dose of FLX (2.5 mg/kg, -23,-5 and -1 h) was evaluated. The results showed that RU 58668, the antagonist to the ER, canceled the antidepressant-like action of E2 in a dose-dependent manner. The antagonist to the 5-HT1A receptor blocked the antidepressant action of FLX only when administered simultaneously with FLX, i.e. -23, -5 and -1 h before the FST. Finally, the administration of both RU 58668, and WAY100635 canceled the antidepressant-like action of the combination of E2/FLX. These results imply that both 5-HT1A receptors and ERs participate in the

  17. The Post-Ovariectomy Interval Affects the Antidepressant-Like Action of Citalopram Combined with Ethynyl-Estradiol in the Forced Swim Test in Middle Aged Rats

    PubMed Central

    Vega Rivera, Nelly M.; Gallardo Tenorio, Alfredo; Fernández-Guasti, Alonso; Estrada Camarena, Erika

    2016-01-01

    The use of a combined therapy with low doses of estrogens plus antidepressants to treat depression associated to perimenopause could be advantageous. However the use of these combinations is controversial due to several factors, including the time of intervention in relation to menopause onset. This paper analyzes whether time post-OVX influences the antidepressant-like action of a combination of ethynyl-estradiol (EE2) and citalopram (CIT) in the forced swim test (FST). Middle-aged (15 months old) female Wistar rats were ovariectomized and after one or three weeks treated with EE2 (1.25, 2.5 or 5.0 µg/rat, s.c.; −48 h) or CIT (1.25, 2.5, 5.0 or 10 mg/kg, i.p./3 injections in 24 h) and tested in the FST. In a second experiment, after one or three weeks of OVX, rats received a combination of an ineffective dose of EE2 (1.25 µg/rat, s.c., −48 h) plus CIT (2.5 mg/kg, i.p./3 injections in 24 h) and subjected to the FST. Finally, the uteri were removed and weighted to obtain an index of the peripheral effects of EE2 administration. EE2 (2.5 or 5.0 µg/rat) reduced immobility after one but not three weeks of OVX. In contrast, no CIT dose reduced immobility at one or three weeks after OVX. When EE2 (1.25 µg/rat) was combined with CIT (2.5 mg/kg) an antidepressant-like effect was observed at one but not three weeks post-OVX. The weight of the uteri augmented when EE2 was administrated three weeks after OVX. The data suggest that the time post-OVX is a crucial factor that contributes to observe the antidepressant-like effect of EE2 alone or in combination with CIT. PMID:27153072

  18. Effects of imipramine and bupropion on the duration of immobility of ACTH-treated rats in the forced swim test: involvement of the expression of 5-HT2A receptor mRNA.

    PubMed

    Kitamura, Yoshihisa; Fujitani, Yoshika; Kitagawa, Kouhei; Miyazaki, Toshiaki; Sagara, Hidenori; Kawasaki, Hiromu; Shibata, Kazuhiko; Sendo, Toshiaki; Gomita, Yutaka

    2008-02-01

    We examined the effect of chronic administration of imipramine and bupropion, monoamine reuptake inhibitors, on the duration of immobility in the forced swim test and serotonin (5-HT)(2A) receptor function in the form of 5-HT(2A) receptor mRNA levels in rats chronically treated with adrenocorticotropic hormone (ACTH). The immobility-decreasing effect of bupropion without imipramine did not influence the chronic ACTH treatment. The effect on the expression of 5-HT(2A) receptor mRNA of chronic ACTH treatment was decreased by bupropion, but not imipramine. These results suggest that bupropion has the effect of reducing immobility time in the forced swim test in the tricyclic antidepressant-resistant depressive model induced by chronic ACTH treatment in rats, and that decreased 5-HT(2A) receptor mRNA levels may be involved in this phenomenon.

  19. A comparative pharmacological investigation of three samples of 'Guduchi ghrita' for adaptogenic activity against forced swimming induced gastric ulceration and hematological changes in albino rats.

    PubMed

    Savrikar, Shriram S; Dole, Vilas; Ravishankar, B; Shukla, Vinay J

    2010-04-01

    This study was undertaken to investigate the impact of formulation factors and adjuvants on the expression of biological activity of Tinospora cordifolia (Willd.) Miers. The adaptogenic effect of three samples of Guduchi ghrita, prepared using plain ghee (clarified butter) obtained from three different sources was studied in albino rats and compared with expressed juice of stem of Guduchi. The test preparations were evaluated against forced-swimming induced hypothermia, gastric ulceration and changes in the hematological parameters. The test drug given in the form of 'ghrita' produced better effect in comparison to the expressed juice. Among the three 'ghrita' preparations evaluated, only the 'Solapur Guduchi ghrita' (SGG) was found to produce significant inhibition of stress hypothermia and gastric ulceration. The other two preparations 'Nanded Guduchi ghrita' (NGG), and 'Wardha Guduchi ghrita' (WGG) could produce only a marginal effect. In hematological parameters 'Guduchi' juice produced better reversal of the stress-induced changes in comparison to the test 'ghrita' preparations. The present study provides evidence highlighting the importance of formulation factors for the expression of biological activity. PMID:20814518

  20. Antidepressant-like effects of mGluR1 and mGluR5 antagonists in the rat forced swim and the mouse tail suspension tests.

    PubMed

    Belozertseva, I V; Kos, T; Popik, P; Danysz, W; Bespalov, A Y

    2007-02-01

    Drugs that act to reduce glutamatergic neurotransmission such as NMDA receptor antagonists exert antidepressant-like effects in a variety of experimental paradigms, but their therapeutic application is limited by undesired side effects. In contrast, agents that reduce glutamatergic tone by blocking type I metabotropic glutamate receptors have been suggested to have more a favorable side-effect profile. The present study aimed to compare the effects of mGluR1 antagonist (EMQMCM; JNJ16567083, 3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate, 0.156-10 mg/kg) and mGluR5 antagonist (MTEP, [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine, 1.25-10 mg/kg) in two behavioral screening assays commonly used to assess antidepressant-like activity. In the modified forced swim test in rats, imipramine (used as a positive control) decreased immobility (MED 40 mg/kg) and increased the duration of escape-oriented (climbing and diving; MED 20 mg/kg) behaviors. Both EMQMCM and MTEP decreased the floating duration (MED 1.25 and 2.5 mg/kg) and increased the duration of mobile behaviors (paddling and swimming; MED 2.5 and 5 mg/kg). EMQMCM but not MTEP increased the duration of escape behaviors (climbing and diving; MED 1.25 mg/kg). In the mouse tail suspension test, EMQMCM (5 but not 2.5, 10 and 25 mg/kg), 2-methyl-6-(phenylethynyl)-pyridine (MPEP, 10 but not 1 mg/kg) and MTEP (MED 25 mg/kg) decreased immobility scores. For EMQMCM, the dose-effect relationship was biphasic. With the exception of EMQMCM (10 mg/kg), locomotor activity in mice was not affected by treatments. The present study therefore suggests that acute blockade of mGluR5 and also of mGluR1 exerts antidepressant-like effects in behavioral despair tests in rats and mice.

  1. N-3 polyunsaturated fatty acid consumption produces neurobiological effects associated with prevention of depression in rats after the forced swimming test.

    PubMed

    Park, Yongsoon; Moon, Hyoun-Jung; Kim, Seok-Hyeon

    2012-08-01

    Epidemiological data and clinical trials suggest that n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have preventive and therapeutic effects on depression; however, the underlying mechanism remains elusive. The present study aimed to examine the behavioral effects and antidepressant mechanism of n-3 PUFA using a forced swimming test. Eleven-week-old male Sprague-Dawley rats were fed an American Institute of Nutrition-93M diet containing 0%, 0.5% or 1% EPA and DHA relative to the total energy intake in their diet for 12 weeks (n=8 per group). Total dietary intake, body weight and hippocampus weights were not significantly different among groups. The groups administered 0.5% and 1% EPA+DHA diets had significantly higher levels of n-3 PUFA in their brain phospholipids compared to those in the control group. The immobility time was significantly decreased and the climbing time was significantly increased in the 0.5% and 1% EPA+DHA groups compared with those in the 0% EPA+DHA group. Plasma serotonin concentration and hippocampus c-AMP response element binding protein (CREB) expression were significantly increased in the 0.5% and 1% EPA+DHA groups compared with those in the 0% EPA+DHA group. Conversely, interleukin (IL)-6 expression was significantly reduced in the 0.5% and 1% EPA+DHA groups compared with that in the 0% EPA+DHA group. However, there were no dose-dependent effects of n-3 PUFA and no significant differences in expressions of IL-1β, tumor necrosis factor-α, brain-derived neurotrophic factor or phosphorylated CREB. In conclusion, long-term intake of EPA+DHA induced antidepressant-like effects in rats and overexpression of CREB via decreased IL-6 expression.

  2. Influence of the brain sexual differentiation process on despair and antidepressant-like effect of fluoxetine in the rat forced swim test.

    PubMed

    Gómez, M L; Martínez-Mota, L; Estrada-Camarena, E; Fernández-Guasti, A

    2014-03-01

    Sex differences exist in the depressive disorder prevalence and response to treatment. Several studies suggest that females respond better than males to the action of selective serotonin reuptake inhibitors (SSRIs), suggesting that gonadal hormones modulate mood and the response to these drugs. Sexual steroid hormones exert organizational actions (perennial and on early development) and activational effects (transient and on differentiated tissues). The aim of this study was to analyze sex differences in the forced swim test (FST) in animals without treatment and after fluoxetine (FLX, 0, 2.5, 5.0 and 10.0mg/kg). Initially, we compared male and female adult rats under control conditions or after altering their sexual differentiation process (at day 5 postnatally, PN, 60μg of testosterone propionate to females and male castration to induce or preclude masculinization, respectively). To further analyze if the sex differences depend on organizational or activational steroid hormone action we tested the same animals before and after adult gonadectomy. To prevent variations depending upon the estrous cycle, control and masculinized females were tested in estrus. Control females showed lower immobility and required lower doses of FLX (5mg/kg), to show an antidepressant-like effect, than males (10mg/kg), even after adult gonadectomy. In control males adult orchidectomy prevented FLX's action. Neonatally masculinized females exhibited analogous levels of immobility than control ones; before ovariectomy they responded to FLX similar to controls, but after the surgery they did not respond to fluoxetine. Neonatally orchidectomized males exhibited similar immobility values and response to FLX than control females. The findings suggest that the sex difference in despair depends on the hormones organizational effects and, in males, the response to FLX relies on organizational and activational actions.

  3. Resistive force theory for sand swimming

    NASA Astrophysics Data System (ADS)

    Ding, Yang; Maladen, Ryan; Li, Chen; Goldman, Daniel

    2009-11-01

    We discuss a resistive force theoryfootnotetextMaladen et. al, Science, 325, 314, 2009 that predicts the ratio of forward speed to wave speed (wave efficiency, η) of the sandfish lizard as it swims in granular media of varying volume fraction φ using a sinusoidal traveling wave body motion. In experiment η 0.5 independent of φ and is intermediate between η 0.2 for low Re Newtonian fluid undulatory swimmers like nematodes and η 0.9 for undulatory locomotion on a deformable surface. To predict η in granular media, we developed a resistive force model which balances thrust and drag force over the animal profile. We approximate the drag forces by measuring the force on a cylinder (a ``segment'' of the sandfish) oriented at different angles relative to the displacement direction. The model correctly predicts that η is independent of φ because the ratio of thrust to drag is independent of φ. The thrust component of the drag force is relatively larger in granular media than in low Re fluids, which explains why η in frictional granular media is greater than in viscous fluids.

  4. Tethered swimming can be used to evaluate force contribution for short-distance swimming performance.

    PubMed

    Morouço, Pedro G; Marinho, Daniel A; Keskinen, Kari L; Badillo, Juan J; Marques, Mário C

    2014-11-01

    The purpose of this study was two-fold: (a) to compare stroke and the physiological responses between maximal tethered and free front crawl swimming and (b) to evaluate the contribution of force exertion for swimming performance over short distances. A total of 34 male swimmers, representing various levels of competitive performance, participated in this study. Each participant was tested in both a 30-second maximal tethered swimming test and a 50-m free swimming test. The tethered force parameters, the swimming speed, stroke (stroke rate [SR]), and the physiological responses (increase in blood lactate concentration [ΔBLa], heart rate, and rate of perceived exertion) were recorded and calculated. The results showed no differences in stroke and the physiological responses between tethered and free swimming, with a high level of agreement for the SR and ΔBLa. A strong correlation was obtained between the maximum impulse of force per stroke and the speed (r = 0.91; p < 0.001). Multiple regression analysis revealed that the maximum impulse and SR in the tethered condition explained 84% of the free swimming performance. The relationship between the swimming speed and maximum force tended to be nonlinear, whereas linear relationships were observed with the maximum impulse. This study demonstrates that tethered swimming does not significantly alter stroke and the physiological responses compared with free swimming, and that the maximum impulse per stroke should be used to evaluate the balance between force and the ability to effectively apply force during sprint swimming. Consequently, coaches can rely on tethered forces to identify strength deficits and improve swimming performance over short distances. PMID:24796981

  5. The Effect of Swimming Experience on Acquisition and Retention of Swimming-Based Taste Aversion Learning in Rats

    ERIC Educational Resources Information Center

    Masaki, Takahisa; Nakajima, Sadahiko

    2010-01-01

    Swimming endows rats with an aversion to a taste solution consumed before swimming. The present study explored whether the experience of swimming before or after the taste-swimming trials interferes with swimming-based taste aversion learning. Experiment 1 demonstrated that a single preexposure to 20 min of swimming was as effective as four or…

  6. Requirement of AMPA receptor stimulation for the sustained antidepressant activity of ketamine and LY341495 during the forced swim test in rats.

    PubMed

    Koike, Hiroyuki; Chaki, Shigeyuki

    2014-09-01

    Ketamine, a non-competitive N-methyl-d-aspartate receptor antagonist, and group II metabotropic glutamate (mGlu2/3) receptor antagonists produce antidepressant effects in animal models of depression, which last for at least 24h, through the transient increase in glutamate release, leading to activation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor. Both ketamine and an mGlu2/3 receptor antagonist reportedly increase the expression of GluR1, an AMPA receptor subunit, within 24h, which may account for the sustained enhancement of excitatory synaptic transmission following ketamine administration. However, whether the sustained increase in AMPA receptor-mediated synaptic transmission is associated with the antidepressant effects of ketamine and mGlu2/3 receptor antagonists has not yet been investigated. In the present study, to address this question, we tested whether AMPA receptor stimulation at 24h after a single injection of ketamine or an mGlu2/3 receptor antagonist, (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl)propanoic acid (LY341495) was necessary for the antidepressant effect of these compounds using a forced swim test in rats. A single injection of ketamine or LY341495 at 24h before the test significantly decreased the immobility time. An AMPA receptor antagonist, 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX), administered 30min prior to the test significantly and dose-dependently reversed the antidepressant effects of ketamine and LY341495, while NBQX itself had no effect on the immobility time. Our findings suggest that AMPA receptor stimulation at 24h after a single injection of ketamine or LY341495 is required to produce the anti-immobility effects of these compounds. Moreover, the present results provide additional evidence that an mGlu2/3 receptor antagonist may share some of neural mechanisms with ketamine to exert antidepressant effects.

  7. Open-Space Forced Swim Model of Depression for Mice

    PubMed Central

    Stone, Eric A.; Lin, Yan

    2011-01-01

    This protocol describes a simplified method for inducing a chronic depression-like state in mice that is based on the repeated open-space forced swim method for rats originally developed by Sun and Alkon (2003). The method consists of swimming mice daily in lukewarm water (32-34°C) in rat tub cages 24 × 43 × 23 cm w × h × l, for 15 min/day for 4 days, and thereafter once per week. This procedure produces a progressive decrease in distance swum and a concomitant increase in immobility (floating) in about 70 percent of the mice (Swiss Webster males), both of which persist unaltered for weeks and generalize to other tests of depression (tail suspension). The model has predictive, face and construct validity in that it is responsive to chronic antidepressants and coping responses but not to anxiolytics or antipsychotics, represents an inescapable stress that produces generalized passivity, and is accompanied by changes in neural activity and brain cell proliferation that are characteristic of depression and believed to contribute to the disorder. It is less effective in producing anhedonia than other models probably because it is less stressful. The model has a number of advantages over previous methods in that it utilizes very mild stress, is short in duration, is easily standardized, requires only a video camera and either a manual or automatic behavioral scoring system to measure immobility and distance swum, and can be readily used for time course studies of onset of drug action. Moreover, since it utilizes a greater swimming area than the traditional (Porsolt) method it can be used to study interactions of depressive behavior with behavioral flexibility and perseveration. Finally, its use of mice makes it readily amenable to genetic and molecular analyses. PMID:21207368

  8. Omega-3 fatty acid deficient male rats exhibit abnormal behavioral activation in the forced swim test following chronic fluoxetine treatment: association with altered 5-HT1A and alpha2A adrenergic receptor expression.

    PubMed

    Able, Jessica A; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; McNamara, Robert K

    2014-03-01

    Omega-3 fatty acid deficiency during development leads to enduing alterations in central monoamine neurotransmission in rat brain. Here we investigated the effects of omega-3 fatty acid deficiency on behavioral and neurochemical responses to chronic fluoxetine (FLX) treatment. Male rats were fed diets with (CON, n = 34) or without (DEF, n = 30) the omega-3 fatty acid precursor alpha-linolenic acid (ALA) during peri-adolescent development (P21-P90). A subset of CON (n = 14) and DEF (n = 12) rats were administered FLX (10 mg/kg/d) through their drinking water for 30 d beginning on P60. The forced swimming test (FST) was initiated on P90, and regional brain mRNA markers of serotonin and noradrenaline neurotransmission were determined. Dietary ALA depletion led to significant reductions in frontal cortex docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (-26%, p = 0.0001) and DEF + FLX (-32%, p = 0.0001) rats. Plasma FLX and norfluoxetine concentrations did not different between FLX-treated DEF and CON rats. During the 15-min FST pretest, DEF + FLX rats exhibited significantly greater climbing behavior compared with CON + FLX rats. During the 5-min test trial, FLX treatment reduced immobility and increased swimming in CON and DEF rats, and only DEF + FLX rats exhibited significant elevations in climbing behavior. DEF + FLX rats exhibited greater midbrain, and lower frontal cortex, 5-HT1A mRNA expression compared with all groups including CON + FLX rats. DEF + FLX rats also exhibited greater midbrain alpha2A adrenergic receptor mRNA expression which was positively correlated with climbing behavior in the FST. These preclinical data demonstrate that low omega-3 fatty acid status leads to abnormal behavioral and neurochemical responses to chronic FLX treatment in male rats.

  9. 1,2,3,4-Tetrahydroisoquinoline produces an antidepressant-like effect in the forced swim test and chronic mild stress model of depression in the rat: Neurochemical correlates.

    PubMed

    Możdżeń, Edyta; Papp, Mariusz; Gruca, Piotr; Wąsik, Agnieszka; Romańska, Irena; Michaluk, Jerzy; Antkiewicz-Michaluk, Lucyna

    2014-04-15

    1,2,3,4-Tetrahydroisoquinoline (TIQ) is an exo- and endogenous amine naturally present in mammalian brain which displays antidepressant-like effect in various animal models: the forced swim test (FST) and chronic mild stress (CMS) paradigm in rats. To elucidate this action we compared the effects of TIQ with imipramine, a classic antidepressant drug and one of the most clinically effective. Applied behavioral tests showed that TIQ produced an antidepressant-like effect with a potency comparable to that of imipramine. TIQ (25-50mg/kg i.p.), similarly to imipramine (10-30mg/kg i.p.), reduced the immobility time in FST and completely reversed the decrease in sucrose intake caused by CMS in the rat. In addition, in order to avoid the possible psychostimulating effect of TIQ we examined the influence of its administration on locomotor activity in rats. TIQ, like imipramine, produced a reduction in horizontal locomotor activity. This suggested that TIQ did not have psychostimulant properties and that prolonged swimming in the FST was a result of an increased motivation to escape from the stressful situation. The biochemical analyses have shown that TIQ activates monoaminergic systems as a reversible monoamine oxidase (MAO) inhibitor and free radical scavenger. Beyond the activation of noradrenaline and serotonin systems, TIQ also moderately affects the dopamine system. On the basis of the presented behavioral and biochemical studies we suggest that TIQ is a potential new antidepressant which may be effective for the depression therapy in a clinical setting.

  10. Geometric Aspects of Force Controllability for a Swimming Model

    SciTech Connect

    Khapalov, A. Y.

    2008-02-15

    We study controllability properties (swimming capabilities) of a mathematical model of an abstract object which 'swims' in the 2-D Stokes fluid. Our goal is to investigate how the geometric shape of this object affects the forces acting upon it. Such problems are of interest in biology and engineering applications dealing with propulsion systems in fluids.

  11. Physical activity does not account for the physiological response to forced swim testing.

    PubMed

    Abel, E L

    1994-10-01

    Two experiments were conducted to examine physiological variables associated with the immobility response in the forced swim test. The first study compared the effects of water immersion, treadmill running, and foot shock, and showed that the time-related pattern of reactions to these three conditions, especially those involving lactate, glucose, anion gap (a measure of metabolic acidosis), and carbon dioxide differed significantly. The second study examined the role of food deprivation, and showed that this manipulation does not affect the behavior or physiological response of rats to testing. These results indicate that the physiological changes occurring during the forced swim are not simply due to increased physical activity or stress.

  12. 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

    2009-08-01

    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.

  13. Relationship between tethered forces and the four swimming techniques performance.

    PubMed

    Morouço, Pedro; Keskinen, Kari L; Vilas-Boas, Joao Paulo; Fernandes, Ricardo Jorge

    2011-05-01

    The purpose of the current study was to identify the relationships between competitive performance and tether forces according to distance swam, in the four strokes, and to analyze if relative values of force production are better determinants of swimming performance than absolute values. The subjects (n = 32) performed a 30 s tethered swimming all-out effort. The competitive swimming velocities were obtained in the distances 50, 100 and 200 m using official chronometric values of competitions within 25 days after testing protocol. Mean force and velocity (50 m event) show significant correlations for front crawl (r = .92, p < .01), backstroke (r = .81, p < .05), breaststroke (r = .94, p < .01) and butterfly (r = .92, p < .01). The data suggests that absolute values of force production are more associated to competitive performance than relative values (normalized to body mass). Tethered swimming test seems to be a reliable protocol to evaluate the swimmer stroking force production and a helpful estimator of competitive performance in short distance competitive events. PMID:21576725

  14. Neonatal treatment with clomipramine increased immobility in the forced swim test: an attribute of animal models of depression.

    PubMed

    Velazquez-Moctezuma, J; Diaz Ruiz, O

    1992-08-01

    The forced swimming test in rats has been identified as a suitable model for detecting antidepressant activity of several drugs regardless of their mode of action. On the other hand, a number of animal models of human endogenous depression have been proposed. Recently, it has been reported that perinatal administration of clomipramine in rats elicits behavioral changes in adulthood that resemble human endogenous depression. In the present study, we showed that in this new animal model of depression immobility was increased when animals were submitted to the forced swimming test. This finding supports the notion that the amount of immobility during the forced swimming test is directly proportional to a depressive state in the rat.

  15. Antidepressant-like effect of different estrogenic compounds in the forced swimming test.

    PubMed

    Estrada-Camarena, Erika; Fernández-Guasti, Alonso; López-Rubalcava, Carolina

    2003-05-01

    The present study evaluated the possible antidepressant-like action of the natural estrogen 17beta-estradiol (E(2), 2.5-10 microg/rat), the synthetic steroidal estrogen ethinyl-estradiol (EE(2), 1.25-10.0 microg/rat), and the nonsteroidal synthetic estrogen, diethyl-stilbestrol (DES, 0.25-1.0 mg/rat) in ovariectomized adult female Wistar rats using the forced swimming test (FST). The behavioral profile induced by the estrogens was compared with that induced by the antidepressants fluoxetine (FLX, 2.5-10 mg/kg) and desipramine (DMI, 2.5-10 mg/kg). In addition, the temporal course of the antidepressant-like action of the estrogenic compounds was analyzed. FLX and DMI induced an antidepressant-like effect characterized by a reduced immobility and increased swimming for FLX and decreased immobility and increased climbing for DMI. Both E(2) and EE(2) produced a decrease in immobility and an increase in swimming, suggesting an antidepressant-like action. DES did not affect the responses in this animal model of depression at any dose tested. The time course analysis of the actions of E(2) (10 microg/rat) and EE(2) (5 microg/rat) showed that both compounds induced an antidepressant-like effect observed 1 h after their injection lasting for 2-3 days.

  16. Enhanced anti-immobility effects of Sanggenon G isolated from the root bark of Morus alba combined with the α2-antagonist yohimbine in the rat forced swim test.

    PubMed

    Lim, Dong Wook; Baek, Nam-In; Kim, Yun Tai; Lee, Changho; Kim, In-Ho; Han, Daeseok

    2016-07-01

    In this study, we aimed to determine whether Sanggenon G, an active compound isolated from the root bark of Morus alba, exhibited enhanced anti-immobility activity with the addition of the α2-antagonist yohimbine in rats subjected to forced swim test (FST)-induced depression. Fluoxetine (a selective serotonin reuptake inhibitor) treatment in rats reduced the immobility time, and pretreatment with yohimbine significantly enhanced the antidepressant-like behavior of fluoxetine at 5, 10 and 20 mg/kg. Similarly, Sanggenon G significantly decreased the immobility time, reducing immobility by a maximum of 43.9 % when treated at a dose of 20 mg/kg. Furthermore, pretreatment with yohimbine significantly enhanced the antidepressant-like behavior of Sanggenon G at 5 and 10 mg/kg. Our findings suggest that the antidepressant-like effect of Sanggenon G could be facilitated by concomitant use of the α2-antagonist. Further studies are needed to evaluate the potential of Sanggenon G as an alternative therapeutic approach for the treatment of depression.

  17. Reversal of myo-inositol metabolic level in the left dorsolateral prefrontal cortex of rats exposed to forced swimming test following desipramine treatment: an in vivo localized (1)H-MRS study at 4.7 T.

    PubMed

    Kim, Sang-Young; Choi, Chi-Bong; Lee, Hyun-Sung; Lee, Sung-Ho; Woo, Dong-Cheol; Kim, Hwi-Yool; Hong, Kwan-Soo; Lee, Chul-Hyun; Choe, Bo-Young

    2010-12-01

    The forced swimming test (FST) is a useful paradigm that is relatively quick and simple to perform and has been utilized to predict antidepressant activity based on learned helplessness as a model of depression. To date, few studies have used proton magnetic resonance spectroscopy ((1)H-MRS) to assess antidepressant effects in rats. The purpose of this study was to assess desipramine (DMI) effects on the left dorsolateral prefrontal cortex (DLPFC) of the rats, which were randomly assigned to three groups (control, n=10; FST+saline, n=10; FST+DMI, n=10), using single-voxel localization technique. All (1)H-MRS experiments were performed on a Bruker 4.7-T scanner with 400 mm bore magnet, allowing for acquisition of in vivo (1)H point-resolved spectroscopy spectra (TR/TE=3000/30 ms, number of data points=2048, NEX=512, voxel volume=27 μl, scan time=25 min). Proton metabolites were quantified automatically using LCModel software and were expressed as ratios to total creatine (Cr+PCr). Major target metabolites such as N-acetyl aspartate (NAA)+N-acetylaspartylglutamate (NAAG), glutamate+glutamine (Glu+Gln), glycerophosphorylcholine+phosphorylcholine (GPC+PCho), myo-inositol (mIns) and taurine (Tau) were successfully quantified with Cramer-Rao lower boundary ≤10%. There were significantly higher mIns/(Cr+PCr) and mIns/(NAA+NAAG) ratios in the FST+saline group compared to the control group. In the FST+DMI group, both mIns/(Cr+PCr) and mIns/(NAA+NAAG) ratios were significantly decreased to the level similar to those in the control group. No other metabolite ratios were significantly different among the three groups. Our findings suggest a possible role of altered mIns level within the left DLPFC of the rat model for depression. PMID:20817439

  18. Swimming exercise attenuates psychological dependence and voluntary methamphetamine consumption in methamphetamine withdrawn rats

    PubMed Central

    Damghani, Fatemeh; Bigdeli, Imanollah; Miladi-Gorji, Hossein; Fadaei, Atefeh

    2016-01-01

    Objective(s): This study evaluated the effect of swimming exercise during spontaneous methamphetamine (METH) withdrawal on the anxiety, depression, obsessive-compulsive disorder (OCD) and voluntary METH consumption in METH-dependent rats. Materials and Methods: Male Wistar rats were repeatedly administered with bi-daily doses of METH (2 mg/kg, subcutaneous) over a period of 14 days. Exercised rats were submitted to swimming sessions (45 min/day, five days per week, for 14 days) during spontaneous METH-withdrawal. Then, all animals were tested for the assessment of anxiety by using the elevated plus-maze (EPM), the grooming behaviors (OCD), and depression using forced swimming test (FST) and voluntary METH consumption using a two-bottle choice (TBC) paradigm for the assessment of craving. Results: The results showed that the swimmer METH-withdrawn rats exhibited an increase in EPM open arm time and entries and a reduction of immobility and grooming behaviors compared with the sedentary METH groups. Also, voluntary METH consumption was less in the swimmer METH-withdrawn rats than the sedentary METH groups throughout 5–8 days. Conclusion: This study showed that regular swimming exercise reduced voluntary METH consumption in animal models of craving by reducing anxiety, OCD, and depression in the METH-withdrawn rats. Thus, physical training may be ameliorating some of the withdrawal behavioral consequences of METH. PMID:27482339

  19. Individual differences in the elevated plus-maze and the forced swim test.

    PubMed

    Estanislau, Celio; Ramos, Anna Carolina; Ferraresi, Paula Daniele; Costa, Naiara Fernanda; de Carvalho, Heloisa Maria Cotta Pires; Batistela, Silmara

    2011-01-01

    The elevated plus-maze is an apparatus composed of enclosed and open (elevated) arms and time spent in the open arms by a rat can be increased/decreased by anxiolytic/anxiogenic agents. In the forced swim test, floating behavior is used as an index of behavioral despair and can be decreased by antidepressant agents. As the comorbidity between anxiety and depression is a remarkable issue in human behavioral disorders, a possible relationship between the behaviors seen in the cited tests is of great relevance. In the present study, fifty-four male rats (Rattus norvegicus) were submitted to a plus-maze session and to a 2-day forced swim protocol. According to their time in the open arms, they were divided into three groups: Low Open, Medium Open and High Open. Some plus-maze measures were found to be coherent with time in the open arms and are suggested to also be reliable anxiety indexes. In the forced swim test, the Low Open group showed decreases in floating duration from forced swim Session 1 to Session 2, an alteration opposite to that observed in the other groups (particularly, the Medium Open group). The Low Open group also showed increases in floating latency, again in sharp contrast with the alteration found in the other groups. Accordingly, positive and negative correlation were found between time in the open arms and floating duration and latency, respectively. Results are compared to previous studies and mediation of the effect by reactivity to aversive stimulation or alterations induced by open arm exposure is discussed.

  20. Pharmacological mechanisms of antidepressant-like effect of tipepidine in the forced swimming test.

    PubMed

    Kawaura, Kazuaki; Miki, Risa; Urashima, Yuri; Kawahara, Ryo; Soeda, Fumio; Shirasaki, Tetsuya; Takahama, Kazuo

    2012-01-15

    We previously reported that the centrally acting non-narcotic antitussive, tipepidine, produces a novel antidepressant-like effect in the forced swimming test in rats, but the mechanism of the antidepressant-like effect of tipepidine is not clear. We investigated the pharmacological mechanism of the antidepressant-like effect of tipepidine in the forced swimming test in rats. A catecholamine-depleting agent, alpha-methyl-p-tyrosine (AMPT; 300 mg/kg, s.c.), was given 6h before the first injection and with the last injection of tipepidine (40 mg/kg, i.p.). A serotonin (5-HT)-depleting agent, p-chlorophenylalanine (PCPA; 350 mg/kg, i.p.), was given 72 h and 48 h before the pretest session. The dopamine D(1) receptor antagonist, SCH23390 (0.02 mg/kg, s.c.) was given 15min before each of the three injections of tipepidine. The dopamine D(2) receptor antagonist raclopride (0.2mg/kg, s.c.), the alpha 1 adrenoceptor antagonist prazosin (1mg/kg, i.p.), the alpha 2 adrenoceptor antagonist yohimbine (2mg/kg, i.p.) and the beta adrenoceptor antagonist propranolol (2mg/kg, i.p.) were given 30 min before each of the three injections of tipepidine. AMPT, but not PCPA, significantly inhibited the immobility time-reducing effect of tipepidine in the forced swimming test. Furthermore, the effect of tipepidine was significantly inhibited by SCH23390 and yohimbine. However, raclopride, prazosin, and propranolol failed to block the effect of tipepidine. The results suggest that the antidepressant-like effect of tipepidine in the forced swimming test may be due at least in part to the effects of dopamine and noradrenaline released at the dopamine D(1) receptor and alpha 2 adrenoceptor, respectively.

  1. Swimming as a Model of Task-Specific Locomotor Retraining After Spinal Cord Injury in the Rat

    PubMed Central

    Magnuson, David S. K.; Smith, Rebecca R.; Brown, Edward H.; Enzmann, Gaby; Angeli, Claudia; Quesada, Peter M.; Burke, Darlene

    2010-01-01

    Background The authors have shown that rats can be retrained to swim after a moderately severe thoracic spinal cord contusion. They also found that improvements in body position and hindlimb activity occurred rapidly over the first 2 weeks of training, reaching a plateau by week 4. Overground walking was not influenced by swim training, suggesting that swimming may be a task-specific model of locomotor retraining. Objective To provide a quantitative description of hindlimb movements of uninjured adult rats during swimming, and then after injury and retraining. Methods The authors used a novel and streamlined kinematic assessment of swimming in which each limb is described in 2 dimensions, as 3 segments and 2 angles. Results The kinematics of uninjured rats do not change over 4 weeks of daily swimming, suggesting that acclimatization does not involve refinements in hindlimb movement. After spinal cord injury, retraining involved increases in hindlimb excursion and improved limb position, but the velocity of the movements remained slow. Conclusion These data suggest that the activity pattern of swimming is hardwired in the rat spinal cord. After spinal cord injury, repetition is sufficient to bring about significant improvements in the pattern of hindlimb movement but does not improve the forces generated, leaving the animals with persistent deficits. These data support the concept that force (load) and pattern generation (recruitment) are independent and may have to be managed together with respect to postinjury rehabilitation. PMID:19270266

  2. Veratrine blocks the lamotrigine-induced swimming increase and immobility decrease in the modified forced swimming test.

    PubMed

    Codagnone, F T; Consoni, F T; Rodrigues, A L S; Vital, M A B F; Andreatini, R

    2007-08-15

    Lamotrigine exhibits an anti-immobility effect in the modified forced swimming test, increasing swimming and climbing, behaviors that are related to serotonergic and noradrenergic effects, respectively. However, these effects could be secondary to lamotrigine blockade of Na(+) sensitive channel. Thus, this study investigated the influence of veratrine (0.1 mg/kg, ip, 10 min before each lamotrigine administration), an Na(+) channel activator, in the effect of lamotrigine (20 mg/kg, ip, 24, 5, 1 h before the test session) in the modified forced swimming test. Veratrine pre-treatment blocked lamotrigine-induced immobility decrease and swimming increase but it did not change the effect of lamotrigine on climbing. These results suggest that the serotonergic effect of lamotrigine in the modified forced swimming test is dependent on Na(+) voltage sensitive channel blockade, whereas its noradrenergic effect is not.

  3. [Effect of forced swimming on the memory track retention in mice with various behavioral stereotypes].

    PubMed

    Dubrovina, N I; Loskutova, L V; Savost'ianova, D A

    2003-08-01

    The effects of forced swimming on retrieval of the passive avoidance during its extinction were found to depend on aggressive and submissive behavior. In mice without generated behavioral stereotypes, swim stress applied before or after training stabilized retention of the memory trace retrieval. The similar improved influence of forced swimming on memory storage is revealed in submissive, but not aggressive mice. The increase of resistance against extinction under the swim stress can be connected to facilitation of emotional processes.

  4. A forced damped oscillation framework for undulatory swimming provides new insights into how propulsion arises in active and passive swimming.

    PubMed

    Bhalla, Amneet Pal Singh; Griffith, Boyce E; Patankar, Neelesh A

    2013-01-01

    A fundamental issue in locomotion is to understand how muscle forcing produces apparently complex deformation kinematics leading to movement of animals like undulatory swimmers. The question of whether complicated muscle forcing is required to create the observed deformation kinematics is central to the understanding of how animals control movement. In this work, a forced damped oscillation framework is applied to a chain-link model for undulatory swimming to understand how forcing leads to deformation and movement. A unified understanding of swimming, caused by muscle contractions ("active" swimming) or by forces imparted by the surrounding fluid ("passive" swimming), is obtained. We show that the forcing triggers the first few deformation modes of the body, which in turn cause the translational motion. We show that relatively simple forcing patterns can trigger seemingly complex deformation kinematics that lead to movement. For given muscle activation, the forcing frequency relative to the natural frequency of the damped oscillator is important for the emergent deformation characteristics of the body. The proposed approach also leads to a qualitative understanding of optimal deformation kinematics for fast swimming. These results, based on a chain-link model of swimming, are confirmed by fully resolved computational fluid dynamics (CFD) simulations. Prior results from the literature on the optimal value of stiffness for maximum speed are explained. PMID:23785272

  5. Orchiectomy modifies the antidepressant-like response of nicotine in the forced swimming test.

    PubMed

    Bonilla-Jaime, H; Limón-Morales, O; Arteaga-Silva, M; Hernández-González, M; Guadarrama-Cruz, G; Alarcón-Aguilar, F; Vázquez-Palacios, G

    2010-11-01

    Several studies have demonstrated that nicotine (NIC) exhibits antidepressant-like effects. In addition, it has been suggested that sexual hormones participate in the antidepressant actions of antidepressives. The present study was designed to analyze the effect of orchiectomy and the supplementation of testosterone propionate (TP) or 17β-estradiol (E(2)) on the antidepressant properties of NIC using the forced swimming test (FST), as well as to determine possible changes in the FST during different time periods after orchiectomy. In order to evaluate the influences of orchiectomy on the effects of NIC, the study first evaluated the effects of different time periods on orchiectomized rats (15, 21, 30, 45 and 60 days) that were subjected to the FST. Then, different doses of NIC (0.2, 0.4, 0.8, 1.6 mg/kg, sc) were administered for 14 days to both intact and orchiectomized rats (after 21 day) which were then also subjected to the FST. Finally, the influence of the TP or E(2) supplementation on the antidepressant-like effect of NIC on orchiectomized rats (after 21 days) was also analyzed. Results reveal that orchiectomy significantly increased immobility behavior and decreased swimming and climbing up to 60 days after castration. In contrast, NIC decreased immobility behavior and increased swimming in intact rats; whereas orchiectomy suppressed this antidepressant effect of NIC. Only with E(2) supplementation was it possible to restore the sensitivity of the castrated rats to NIC. These results suggest that E(2) was able to facilitate the antidepressant response of NIC in orchiectomized rats.

  6. The antidepressant activity of inositol in the forced swim test involves 5-HT(2) receptors.

    PubMed

    Einat, H; Clenet, F; Shaldubina, A; Belmaker, R H; Bourin, M

    2001-01-01

    The effect of inositol as an antidepressant was previously demonstrated in both animal models of depression-like behavior and in clinical trials. Unlike most antidepressant drugs, inositol does not have a clear target in the synapse and was not demonstrated to alter monoamine levels in the brain. The present study attempted to draw a psychopharmacological profile of inositol's behavioral effects by exploring the interactions between the drug and specific receptor agonists and antagonists in the forced swim test. Rats received inositol treatment (or control) in combination with the serotonergic metabolism inhibitor PCPA or with the noradrenergic neurotoxin DSP-4. Results indicated that PCPA but not DSP-4 abolished the ability of inositol to cause a reduction in immobility time in the forced swim test. In mice, the specific 5-HT(2A)/5-HT(2C) antagonist ritanserin, but not the 5-HT(1A)/5-HT(1B)/beta adrenergic antagonist pindolol, abolished inositol's effect in the forced swim test. The 5-HT(2A)/5-HT(2C) agonist DOI and the 5-HT(1A) agonist 8-OH-DPAT did not have any significant effects on inositol's activity. The present data indicates that the antidepressant effect of inositol may involve 5-HT(2) receptors. It is thus possible that the effects of reuptake antidepressant drugs and the effects of inositol may have a common final pathway.

  7. Effect of bacoside extract from Bacopa monniera on physical fatigue induced by forced swimming.

    PubMed

    Anand, T; Phani Kumar, G; Pandareesh, M D; Swamy, M S L; Khanum, Farhath; Bawa, A S

    2012-04-01

    The antifatigue effect of bacoside extract (BME) from Bacopa monniera (L.) Wettst. was investigated. Rats were subjected to weight-loaded forced swim test (WFST) every alternate day for 3 weeks. The BME at a dosage of 10 mg/kg body weight was administered orally to rats for 2 weeks in order to evaluate the following biomarkers of physical fatigue: swimming time, change in body weight, lipid peroxidation, lactic acid (LA), glycogen, antioxidant enzyme activities such as superoxide dismutase (SOD) and catalase (CAT) and blood parameters, namely blood urea nitrogen (BUN) and creatine kinase (CK). The exhaustive swimming time was increased by 3-fold in the BME supplemented group compared with that of the control group on day 13. The BME treatment lowered malondialdehyde (MDA) levels in brain, liver and muscle tissues by 11.2%, 16.2% and 37.7%, respectively, compared with the control exercised group (p < 0.05). The BME also reduced the LA, serum BUN and CK activities significantly compared with that of the control. Administration of BME significantly protected the depletion of SOD and CAT activities. The HSP-70 expression studies by western blot also confirmed the antifatigue property of BME. The present study thus indicates that BME ameliorates the various impairments associated with physical fatigue.

  8. Intensity of swimming exercise influences aortic reactivity in rats

    PubMed Central

    Brito, A.F.; Silva, A.S.; Souza, I.L.L.; Pereira, J.C.; da Silva, B.A.

    2015-01-01

    Exercise is known to cause a vasodilatory response; however, the correlation between the vasorelaxant response and different training intensities has not been investigated. Therefore, this study evaluated the vascular reactivity and lipid peroxidation after different intensities of swimming exercise in rats. Male Wistar rats (aged 8 weeks; 250-300 g) underwent forced swimming for 1 h whilst tied to loads of 3, 4, 5, 6, and 8% of their body weight, respectively (groups G3, G4, G5, G6 and G8, respectively; n=5 each). Immediately after the test, the aorta was removed and suspended in an organ bath. Cumulative relaxation in response to acetylcholine (10−12-10−4 M) and contraction in response to phenylephrine (10−12-10−5 M) were measured. Oxidative stress was estimated by determining malondialdehyde concentration. The percentages of aorta relaxation were significantly higher in G3 (7.9±0.20), G4 (7.8±0.29), and G5 (7.9±0.21), compared to the control group (7.2±0.04), while relaxation in the G6 (7.4±0.25) and G8 (7.0±0.06) groups was similar to the control group. In contrast, the percentage of contraction was significantly higher in G6 (8.8 ±0.1) and G8 (9.7±0.29) compared to the control (7.1±0.1), G3 (7.3±0.2), G4 (7.2±0.1) and G5 (7.2±0.2%) groups. Lipid peroxidation levels in the aorta were similar to control levels in G3, G4 and G5, but higher in G6 and G8, and significantly higher in G8 (one-way ANOVA). These results indicate a reduction in vasorelaxing activity and an increase in contractile activity in rat aortas after high-intensity exercise, followed by an increase in lipid peroxidation. PMID:26397974

  9. Swimming of pregnant rats at different water temperatures.

    PubMed

    Osorio, R A L; Silveira, V L F; Maldjian, S; Morales, A; Christofani, J S; Russo, A K; Silva, A C; Piçarro, I C

    2003-08-01

    We studied the chronic effect of exercise during water immersion, associated with thermal stress (water temperature at 22, 35 and 40 degrees C) at an intensity of 80% of maximal work load supported in pregnant rats (P) and non-pregnant female rats (NP). P and NP were subdivided into three subgroups according to water temperature during exercise (P22 and NP22; P35 and NP35; P40 and NP40). The animals were submitted to daily swimming sessions of 10-15 min, for 19 days of pregnancy (P) or experimental conditions (NP). Plasma concentration of triglycerides, cholesterol, glucose, total protein, albumin and corticosterone were determined 24 h after the last exercise session. Weight gain and rectal temperature pre- and post-swimming session were also determined. The offspring were examined just after caesarian section on the 20th day of pregnancy to check weight, length and litter size. Pregnant rats showed an increase of triglycerides, reduction of glycemia, total protein and albumin and cholesterol (at 35 degrees C) when compared to non-pregnant animals. Such effects probably lead to an adequate delivery of substrate to the fetus and prepare the mother for lactation. Daily thermal stress did not modify metabolic responses to exercise in pregnant rats. Results also show a deleterious effect on offspring when the mother is exposed daily to extreme temperatures during swimming. These results suggest that water temperature (cold and hot) in swimming have to be considered to avoid damage in fetal development.

  10. Noradrenergic lesions differentially alter the antidepressant-like effects of reboxetine in a modified forced swim test.

    PubMed

    Cryan, John F; Page, Michelle E; Lucki, Irwin

    2002-02-01

    The novel antidepressant reboxetine is a selective norepinephrine reuptake inhibitor. In this study, the antidepressant-like effects of reboxetine were characterized in a modified rat forced swim test. Further, in order to investigate the role of the locus coeruleus and lateral tegmental noradrenergic systems in the mediation of reboxetine's effects, the impact of different chemical lesions of these two pathways was examined on the behavioral responses induced by reboxetine in the forced swim test. Reboxetine (5-20 mg/kg, s.c.) dose-dependently decreased immobility and swimming behavior in the forced swim test while it simultaneously increased climbing behavior. These effects were similar to those previously demonstrated with tricyclic antidepressants and are indicative of reboxetine's effects on the noradrenergic system. Discrete local injections of the neurotoxin 6-hydroxydopamine were employed to lesion the ventral noradrenergic bundle arising from cells located in the lateral tegmentum. This resulting lesion completely prevented reboxetine (10 mg/kg, s.c.)-induced decreases in immobility and increases in climbing behavior, demonstrating that an intact ventral noradrenergic bundle is required for the manifestation of reboxetine-induced antidepressant-like behavior in the test. In contrast, lesions of the dorsal noradrenergic bundle which consists of neurons arising from the nucleus locus coereleus, were achieved by systemic pretreatment with the selective noradrenergic neurotoxin N-(2-chloroethyl)-N-2-bromobenzylamine (DSP-4; 50 mg/kg, i.p.). The ability of reboxetine (10 mg/kg, s.c.) to increase climbing and decrease immobility was augmented by DSP-4 pretreatment. Furthermore, neither lesions of the dorsal noradrenergic bundle nor the ventral noradrenergic bundle altered baseline immobility scores in the forced swim test. Taken together, these data suggest that forebrain regions innervated by these two distinct noradrenergic pathways exert opposing influences

  11. The Relationship Between Propulsive Force in Tethered Swimming and 200-m Front Crawl Performance.

    PubMed

    Santos, Karini B; Bento, Paulo C B; Pereira, Gleber; Rodacki, André L F

    2016-09-01

    Santos, KB, Bento, PCB, Pereira, G, and Rodacki, ALF. The relationship between propulsive force in tethered swimming and 200-m front crawl performance. J Strength Cond Res 30(9): 2500-2507, 2016-The aims of this study were to determine whether propulsive force (peak force, mean force, impulse, and rate of force development) and stroke rate change during 2 minutes of front crawl tethered swimming and to correlate them with the stroke rate and swimming velocity in 200-m front crawl swimming. Twenty-one swimmers (21.6 ± 4.8 years, 1.78 ± 0.06 m, 71.7 ± 8.1 kg), with 200-m front crawl swimming performance equivalent to 78% of the world record (140.4 ± 10.1 seconds), were assessed during 2 minutes of maximal front crawl tethered swimming (propulsive forces and stroke rate) and 200-m front crawl swimming (stroke rate and clean velocity). Propulsive forces decreased between the beginning and the middle instants (∼20%; p ≤ 0.05) but remained stable between the middle and the end instants (∼6%; p > 0.05). The peak force was positively correlated with the clean velocity in the 200-m front crawl swimming (mean r = 0.61; p < 0.02). The stroke rates of the tethered swimming and 200-m front crawl swimming were positively correlated (r = 45; p≤ 0.01) at the middle instant. Therefore, the propulsive force and stroke rate changed throughout the 2 minutes of tethered swimming, and the peak force is the best propulsive force variable tested that correlated with 200-m front crawl swimming performance.

  12. Postpartum depression in rats: differences in swim test immobility, sucrose preference and nurturing behaviors.

    PubMed

    Fernandez, Jamie Winderbaum; Grizzell, J Alex; Philpot, Rex M; Wecker, Lynn

    2014-10-01

    Postpartum depression (PPD) is a common disorder affecting both mothers and their offspring. Studies of PPD in laboratory animals have typically assessed either immobility on forced swim testing or sucrose preference in ovariectomized rats following hormone supplementation and withdrawal or in stress models. To date, few studies have related these measures to maternal behaviors, a potential indicator of depressive-like activity postpartum. Because a single measure may be insufficient to characterize depression, the present study determined the distribution of depressive-like behaviors in Sprague-Dawley rats postpartum. Nurturing and non-nurturing behaviors exhibited by undisturbed dams were recorded during the first 12 days postpartum, and immobility in the forced swim test and sucrose preference were determined thereafter. A median-split analysis indicated that 19% of dams exhibited high sucrose preference and low immobility, 30% exhibited either only high immobility or only low sucrose preference, and 21% exhibited both high immobility and low preference. Dams exhibiting depressive-like activity on either or both tests displayed increased self-directed behaviors and decreased active nurturing during the dark phase of the diurnal cycle. This is the first study to characterize undisturbed nurturing and non-nurturing behaviors, and use both sucrose preference and immobility in the forced swim test, to classify PPD endophenotypes exhibited by rat dams following parturition. The present study underscores the idea that multiple tests should be used to characterize depressive-like behavior, which is highly heterogeneous in both the human and laboratory animal populations.

  13. Severe brain hypothermia as a factor underlying behavioral immobility during cold-water forced swim.

    PubMed

    Taltavull, J F; Chefer, V I; Shippenberg, T S; Kiyatkin, E A

    2003-06-13

    Behavioral immobility during forced swim is usually considered a consequence of inescapable stress, and is used to screen antidepressant drugs. However, immobility in this test may also result from inhibition of neural functions because of brain hypothermia due to body cooling. To explore this possibility, we measured brain temperature dynamics during a 10-min forced swim in cold (25 degrees C) and warm (37 degrees C) water and correlated brain temperatures with behavioral changes. Cold water forced swim resulted in significant brain hypothermia (-6-7 degrees C) and immobility, while no immobility was observed during warm water forced swim, when brain temperature transiently increased (0.5 degrees C) then decreased below baseline in the post-swim period. These data suggest that immobility, which rapidly develops during forced swim in cold water, may result from dramatic inhibition of neural functions because of severe brain hypothermia.

  14. Drag force and jet propulsion investigation of a swimming squid

    NASA Astrophysics Data System (ADS)

    Tabatabaei, Mahdi; Bahadır Olcay, Ali; Gokçen, Gökhan; Heperkan, Hasan A.

    2015-05-01

    In this study, CAD model of a squid was obtained by taking computer tomography images of a real squid. The model later placed into a computational domain to calculate drag force and performance of jet propulsion. The drag study was performed on the CAD model so that drag force subjected to real squid was revealed at squid's different swimming speeds and comparison has been made with other underwater creatures (e.g., a dolphin, sea lion and penguin). The drag coefficient (referenced to total wetted surface area) of squid is 0.0042 at Reynolds number 1.6x106 that is a %4.5 difference from Gentoo penguin. Besides, jet flow of squid was simulated to observe the flow region generated in the 2D domain utilizing dynamic mesh method to mimic the movement of squid's mantle cavity.

  15. Swimming-Induced Taste Aversion and Its Prevention by a Prior History of Swimming

    ERIC Educational Resources Information Center

    Masaki, Takahisa; Nakajima, Sadahiko

    2004-01-01

    In two experiments, the evidence showed that 20 min of forced swimming by rats caused aversion to a taste solution consumed before swimming. When one of two taste solutions (sodium saccharin or sodium chloride, counterbalanced across rats) was paired with swimming and the other was not, the rats' intakes of these two solutions showed less…

  16. Antidepressant-like effect of centrally acting non-narcotic antitussive caramiphen in a forced swimming test.

    PubMed

    Kawaura, Kazuaki; Miki, Risa; Shima, Eriko; Honda, Sokichi; Soeda, Fumio; Shirasaki, Tetsuya; Takahama, Kazuo

    2010-09-13

    Recently, we reported that a centrally acting non-narcotic antitussive (cough suppressant drug), tipepidine produces an antidepressant-like effect in the forced swimming test in rats. Because pharmacological properties of tipepidine apparently differ from those of typical antidepressants developed to date, we speculated that caramiphen, another centrally acting antitussive, has an antidepressant-like effect. That effect of caramiphen was studied in rats using the forced swimming test. Caramiphen at 20 and 40mg/kg i.p. significantly reduced immobility. At 40mg/kg i.p., it increased climbing behavior. Even at 40mg/kg, this drug had no effect on locomotor activity. Results suggest that a centrally acting antitussive possessing inhibition of GIRK channels has an antidepressant-like effect. PMID:20621160

  17. Antidepressant-like effect of centrally acting non-narcotic antitussive caramiphen in a forced swimming test.

    PubMed

    Kawaura, Kazuaki; Miki, Risa; Shima, Eriko; Honda, Sokichi; Soeda, Fumio; Shirasaki, Tetsuya; Takahama, Kazuo

    2010-09-13

    Recently, we reported that a centrally acting non-narcotic antitussive (cough suppressant drug), tipepidine produces an antidepressant-like effect in the forced swimming test in rats. Because pharmacological properties of tipepidine apparently differ from those of typical antidepressants developed to date, we speculated that caramiphen, another centrally acting antitussive, has an antidepressant-like effect. That effect of caramiphen was studied in rats using the forced swimming test. Caramiphen at 20 and 40mg/kg i.p. significantly reduced immobility. At 40mg/kg i.p., it increased climbing behavior. Even at 40mg/kg, this drug had no effect on locomotor activity. Results suggest that a centrally acting antitussive possessing inhibition of GIRK channels has an antidepressant-like effect.

  18. AMPA Receptor-mTOR Activation is Required for the Antidepressant-Like Effects of Sarcosine during the Forced Swim Test in Rats: Insertion of AMPA Receptor may Play a Role.

    PubMed

    Chen, Kuang-Ti; Tsai, Mang-Hung; Wu, Ching-Hsiang; Jou, Ming-Jia; Wei, I-Hua; Huang, Chih-Chia

    2015-01-01

    Sarcosine, an endogenous amino acid, is a competitive inhibitor of the type I glycine transporter and an N-methyl-d-aspartate receptor (NMDAR) coagonist. Recently, we found that sarcosine, an NMDAR enhancer, can improve depression-related behaviors in rodents and humans. This result differs from previous studies, which have reported antidepressant effects of NMDAR antagonists. The mechanisms underlying the therapeutic response of sarcosine remain unknown. This study examines the role of mammalian target of rapamycin (mTOR) signaling and α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR) activation, which are involved in the antidepressant-like effects of several glutamatergic system modulators. The effects of sarcosine in a forced swim test (FST) and the expression levels of phosphorylated mTOR signaling proteins were examined in the absence or presence of mTOR and AMPAR inhibitors. In addition, the influence of sarcosine on AMPAR trafficking was determined by analyzing the phosphorylation of AMPAR subunit GluR1 at the PKA site (often considered an indicator for GluR1 membrane insertion in neurons). A single injection of sarcosine exhibited antidepressant-like effects in rats in the FST and rapidly activated the mTOR signaling pathway, which were significantly blocked by mTOR inhibitor rapamycin or the AMPAR inhibitor 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) pretreatment. Moreover, NBQX pretreatment eliminated the ability of sarcosine to stimulate the phosphorylated mTOR signaling proteins. Furthermore, GluR1 phosphorylation at its PKA site was significantly increased after an acute in vivo sarcosine treatment. The results demonstrated that sarcosine exerts antidepressant-like effects by enhancing AMPAR-mTOR signaling pathway activity and facilitating AMPAR membrane insertion. Highlights-A single injection of sarcosine rapidly exerted antidepressant-like effects with a concomitant increase in the activation of the mammalian

  19. Effects of swimming activity on the copulatory behavior of sexually active male rats.

    PubMed

    Allouh, M Z

    2015-01-01

    Physical activity has long been associated with better sexual function. This study investigated the effects of moderate swimming exercise on the copulatory behavior of sexually potent male rats. Two sets of sexually potent male rats -highly active and moderately active- were identified depending on baseline sexual activity. Each of the two sets of rats was further randomly divided into two groups (swimming and sedentary). There were 16 rats in each of the four study groups (highly active swimming, highly active sedentary, moderately active swimming and moderately active sedentary). The copulatory behavior parameters and serum testosterone levels were measured and compared between the rats of the swimming and sedentary groups following a month long training period in which rats were made to swim for 1 h every alternate day. Swimming significantly improved the sexual performance of highly active rats, as indicated by increased intromission frequency and intromission ratio, compared with the sedentary controls. Swimming improved both sexual desire and performance, as indicated by reduced mount latency and increased intromission ratio, respectively, in swimming moderately active rats compared with the sedentary moderately active controls. Therefore, swimming activity improves the copulatory behavior of both highly active and moderately active male rats.

  20. Swim test immobility in a genetic rat model of depression is modified by maternal environment: a cross-foster study.

    PubMed

    Friedman, Elliot; Berman, Marissa; Overstreet, David

    2006-03-01

    The Flinders sensitive line (FSL) genetic animal model of depression exhibits marked immobility during forced swimming, an accepted index of depressive like behavior in rodent depression models. The present experiment tested the hypothesis that swim test behavior in the FSL rats is influenced in part by early experience, specifically maternal environment. Male FSL and control Flinders resistant line (FRL) pups were cross fostered onto dams of the same or complementary strain. Nest quality and dam behavior during pup retrieval were measured on PN5 and PN8, and swim test behavior assessed in the adult males on PN60. FSL rats reared by foster FRL dams were significantly less immobile than FSL rats raised by FSL dams, but still significantly more immobile that the two FRL groups, which did not differ from each other. FSL dams took significantly longer to retrieve their pups and dropped them more often than the FRL control dams. Moreover, strain differences in maternal retrieval behavior significantly predicted later swim test immobility in the FSL animals. These findings suggest that swim test immobility in the FSL rats is modified by maternal environment. In contrast, the FRL control rats were relatively insensitive to the influence of maternal environment. The FSL model offers promise for understanding the interactions of genetic vulnerabilities and environmental influences in the etiology of clinical depression.

  1. Gastrodia elata Bl. Attenuated learning deficits induced by forced-swimming stress in the inhibitory avoidance task and Morris water maze.

    PubMed

    Chen, Pei-Ju; Liang, Keng-Chen; Lin, Hui-Chen; Hsieh, Ching-Liang; Su, Kuan-Pin; Hung, Mei-Chu; Sheen, Lee-Yan

    2011-06-01

    This study adopted the forced-swimming paradigm to induce depressive symptoms in rats and evaluated the effects on learning and memory processing. Furthermore, the effects of the water extract of Gastrodia elata Bl., a well-known Chinese traditional medicine, on amnesia in rats subjected to the forced-swimming procedure were studied. Rats were subjected to the forced-swimming procedure, and the inhibitory avoidance task and Morris water maze were used to assess learning and memory performance. The acquisition of the two tasks was mostly impaired after the 15-minute forced-swimming procedure. Administration of the water extract of G. elata Bl. for 21 consecutive days at a dosage of 0.5 or 1.0 g/kg of body weight significantly improved retention in the inhibitory avoidance test, and the lower dose showed a better effect than the higher one and the antidepressant fluoxetine (18 mg/kg of body weight). In the Morris water maze, the lower dose of the water extract of G. elata Bl. significantly improved retention by shortening escape latency in the first test session and increasing the time in searching the target zone during the probe test. These findings suggest that water extracts of G. elata Bl. ameliorate the learning and memory deficits induced by forced swimming.

  2. Factors influencing behavior in the forced swim test.

    PubMed

    Bogdanova, Olena V; Kanekar, Shami; D'Anci, Kristen E; Renshaw, Perry F

    2013-06-13

    The forced swim test (FST) is a behavioral test in rodents which was developed in 1978 by Porsolt and colleagues as a model for predicting the clinical efficacy of antidepressant drugs. A modified version of the FST added the classification of active behaviors into swimming and climbing, in order to facilitate the differentiation between serotonergic and noradrenergic classes of antidepressant drugs. The FST is now widely used in basic research and the pharmaceutical screening of potential antidepressant treatments. It is also one of the most commonly used tests to assess depressive-like behavior in animal models. Despite the simplicity and sensitivity of the FST procedure, important differences even in baseline immobility rates have been reported between different groups, which complicate the comparison of results across studies. In spite of several methodological papers and reviews published on the FST, the need still exists for clarification of factors which can influence the procedure. While most recent reviews have focused on antidepressant effects observed with the FST, this one considers the methodological aspects of the procedure, aiming to summarize issues beyond antidepressant action in the FST. The previously published literature is analyzed for factors which are known to influence animal behavior in the FST. These include biological factors, such as strain, age, body weight, gender and individual differences between animals; influence of preconditioning before the FST: handling, social isolation or enriched environment, food manipulations, various kinds of stress, endocrine manipulations and surgery; schedule and routes of treatment, dosage and type of the drugs as well as experimental design and laboratory environmental effects. Consideration of these factors in planning experiments may result in more consistent FST results.

  3. Swimming Activity Prevents the Unloading Induced Loss of Bone Mass, Architecture, and Strength in Rats

    PubMed Central

    Falcai, Maurício J.; Leoni, Graziela Bianchi; de Sousa Neto, Manoel Damião; Volpon, Jose B.

    2015-01-01

    We investigated whether swimming activity associated with a three-week period of hypoactivity could prevent the deleterious effects of disuse on the tibias of tail-suspended rats. Forty Wistar rats were divided into five groups: (HS) permanently hindlimb suspension rats; (HS + Swim) rats submitted to unloading interrupted by swimming exercise; (HS + WB) hindlimb suspension rats with interruption for regular weight bearing for the same length of time as the HS+Swim rats; (Control) control rats that were allowed regular cage activities; and (Control + Swim) control rats that underwent swimming exercise. At the end of the experiment, bone mineral density, bone strength, and trabecular quantification were analyzed. The hindlimb-suspended rats exhibited bone quality loss (significant decrease in BMD, bone strength, and deterioration of trabecular and cortical bone architecture; decrease in BV/TV, TbN, TbTh, ConnD, CtV, and CtTh; and increase in TbSp) when compared to control rats. In contrast, trained rats showed a significant increase of 43% in bone mass, 29% in bone strength, 58% in trabecular thickness, 85% in bone volume, 27% in trabeculae number, and 30% in cortical volume, when compared to the hindlimb-suspended rats. We conclude that swimming activity not only ameliorates but also fully prevents the deleterious effects on bone quality in osteopenic rats. PMID:26090414

  4. Swimming Activity Prevents the Unloading Induced Loss of Bone Mass, Architecture, and Strength in Rats.

    PubMed

    Falcai, Maurício J; Zamarioli, Ariane; Leoni, Graziela Bianchi; de Sousa Neto, Manoel Damião; Volpon, Jose B

    2015-01-01

    We investigated whether swimming activity associated with a three-week period of hypoactivity could prevent the deleterious effects of disuse on the tibias of tail-suspended rats. Forty Wistar rats were divided into five groups: (HS) permanently hindlimb suspension rats; (HS + Swim) rats submitted to unloading interrupted by swimming exercise; (HS + WB) hindlimb suspension rats with interruption for regular weight bearing for the same length of time as the HS+Swim rats; (Control) control rats that were allowed regular cage activities; and (Control + Swim) control rats that underwent swimming exercise. At the end of the experiment, bone mineral density, bone strength, and trabecular quantification were analyzed. The hindlimb-suspended rats exhibited bone quality loss (significant decrease in BMD, bone strength, and deterioration of trabecular and cortical bone architecture; decrease in BV/TV, TbN, TbTh, ConnD, CtV, and CtTh; and increase in TbSp) when compared to control rats. In contrast, trained rats showed a significant increase of 43% in bone mass, 29% in bone strength, 58% in trabecular thickness, 85% in bone volume, 27% in trabeculae number, and 30% in cortical volume, when compared to the hindlimb-suspended rats. We conclude that swimming activity not only ameliorates but also fully prevents the deleterious effects on bone quality in osteopenic rats.

  5. Calcium metabolism in bone and teeth of rats during exposure to restriction of motor activity and to swimming exercise.

    PubMed

    Zorbas, Y G; Charapakhin, K P; Kuznetsov, N A; Kakurin, V J

    1999-06-01

    The effects of motor activity restriction for 90 days (hypokinesia, HK) and swimming training (T) on calcium metabolism in rat bones and teeth were evaluated. Male Wistar rats were distributed in four groups: untrained vivarium control rats (UVCR), untrained hypokinetic rats (UHKR), trained hypokinetic rats (THKR) and trained vivarium control rats (TVCR). Hypokinesia was obtained keeping the animals for 90 days in small individual cages which restricted their movements in all directions without hindering food and water intakes. Rats of THKR and TVCR were forced to swim for 15 to 90 minutes everyday. On the 1st, 7th, 15th day of a prehypokinetic period and on the 5th, 10th, 20th, 40th, 60th and 90th day of the hypokinetic period, six rats of each group were decapitated. Radioactive calcium was injected to the animals 70 days before autopsy. Calcium and phosphorus in serum, bones (molars, incisors, upper and lower jaws, parietal, scapular, clavicle, pelvic and tibial bones) and in the respective ash residues were measured. Body and bone weights, and radioactive calcium were also determined. Under prolonged exposure to HK (THKR and UHKR groups), bone weights and bone and ash Ca and P concentrations decreased, whereas serum Ca and P and 45Ca resorption increased, in comparison to the respective values in the UVCR and TVCR groups. Swimming exercise apparently did not modify calcium metabolism in the hypokinetic or control rats. PMID:10517263

  6. Decreased body temperature dependent appearance of behavioral despair in the forced swimming test in mice.

    PubMed

    Arai, I; Tsuyuki, Y; Shiomoto, H; Satoh, M; Otomo, S

    2000-08-01

    Effects of body temperature on the immobile response and brain glucose metabolism were examined in the forced swimming test in mice. The first experiment was performed to study behavior, after initial periods of vigorous activity, a characteristic immobile posture occurred when the water was 25 and 35 degrees C. However, several minutes after forced swimming at 25 degrees C, significantly decreased spontaneous motility occurred in a time-dependent manner, but no changes was observed at 35 degrees C. Our interpretation was that mechanisms of acquisition and retention of the forced swim-induced immobile response differed. Body temperature was also significantly decreased at 25 degrees C but not at 35 degrees C in the forced swimming test. This lowering of body temperature almost paralleled the immobile response. The second experiment was a biochemical study in which the uptake of [(14)C] 2-deoxy-d-glucose into the brain significantly decreased after forced swimming at 25 degrees C but did not change in the forced swim loaded mice when the water was 35 degrees C. These results suggested two types of immobile mechanisms in the forced swimming test: (1) an early phase acquisition of the immobile response which might be related to adaptive response and (2) a late phase to retain the immobile response which might be related to the decrease in brain glucose metabolism.

  7. Immobility behavior during the forced swim test correlates with BNDF levels in the frontal cortex, but not with cognitive impairments.

    PubMed

    Borsoi, Milene; Antonio, Camila Boque; Viana, Alice Fialho; Nardin, Patrícia; Gonçalves, Carlos-Alberto; Rates, Stela Maris Kuze

    2015-03-01

    The forced swim test (FST) is widely used to evaluate the antidepressant-like activity of compounds and is sensitive to stimuli that cause depression-like behaviors in rodents. The immobility behavior observed during the test has been considered to represent behavioral despair. In addition, some studies suggest that the FST impairs rats' performance on cognitive tests, but these findings have rarely been explored. Thus, we investigated the effects of the FST on behavioral tests related to neuropsychiatric diseases that involve different cognitive components: novel object recognition (NOR), the object location test (OLT) and prepulse inhibition (PPI). Brain-derived neurotrophic factor (BDNF) levels in the frontal cortex and hippocampus were evaluated. The rats were forced to swim twice (15-min session followed by a 5-min session 24h later) and underwent cognitive tests 24h after the last swimming exposure. The FST impaired the rats' performance on the OLT and reduced the PPI and acoustic startle responses, whereas the NOR was not affected. The cognitive impairments were not correlated with an immobility behavior profile, but a significant negative correlation between the frontal BDNF levels and immobility behavior was identified. These findings suggest a protective role of BDNF against behavioral despair and demonstrate a deleterious effect of the FST on spatial memory and pre-attentive processes, which point to the FST as a tool to induce cognitive impairments analogous to those observed in depression and in other neuropsychiatric disorders. PMID:25496978

  8. Immobility behavior during the forced swim test correlates with BNDF levels in the frontal cortex, but not with cognitive impairments.

    PubMed

    Borsoi, Milene; Antonio, Camila Boque; Viana, Alice Fialho; Nardin, Patrícia; Gonçalves, Carlos-Alberto; Rates, Stela Maris Kuze

    2015-03-01

    The forced swim test (FST) is widely used to evaluate the antidepressant-like activity of compounds and is sensitive to stimuli that cause depression-like behaviors in rodents. The immobility behavior observed during the test has been considered to represent behavioral despair. In addition, some studies suggest that the FST impairs rats' performance on cognitive tests, but these findings have rarely been explored. Thus, we investigated the effects of the FST on behavioral tests related to neuropsychiatric diseases that involve different cognitive components: novel object recognition (NOR), the object location test (OLT) and prepulse inhibition (PPI). Brain-derived neurotrophic factor (BDNF) levels in the frontal cortex and hippocampus were evaluated. The rats were forced to swim twice (15-min session followed by a 5-min session 24h later) and underwent cognitive tests 24h after the last swimming exposure. The FST impaired the rats' performance on the OLT and reduced the PPI and acoustic startle responses, whereas the NOR was not affected. The cognitive impairments were not correlated with an immobility behavior profile, but a significant negative correlation between the frontal BDNF levels and immobility behavior was identified. These findings suggest a protective role of BDNF against behavioral despair and demonstrate a deleterious effect of the FST on spatial memory and pre-attentive processes, which point to the FST as a tool to induce cognitive impairments analogous to those observed in depression and in other neuropsychiatric disorders.

  9. Maternal Forced Swimming Reduces Cell Proliferation in the Postnatal Dentate Gyrus of Mouse Offspring

    PubMed Central

    Wasinski, Frederick; Estrela, Gabriel R.; Arakaki, Aline M.; Bader, Michael; Alenina, Natalia; Klempin, Friederike; Araújo, Ronaldo C.

    2016-01-01

    Physical exercise positively affects the metabolism and induces proliferation of precursor cells in the adult brain. Maternal exercise likewise provokes adaptations early in the offspring. Using a high-intensity swimming protocol that comprises forced swim training before and during pregnancy, we determined the effect of maternal swimming on the mouse offspring's neurogenesis. Our data demonstrate decreased proliferation in sublayers of the postnatal dentate gyrus in offspring of swimming mother at postnatal day (P) 8 accompanied with decreased survival of newly generated cells 4 weeks later. The reduction in cell numbers was predominantly seen in the hilus and molecular layer. At P35, the reduced amount of cells was also reflected by a decrease in the population of newly generated immature and mature neurons of the granule cell layer. Our data suggest that forced maternal swimming at high-intensity has a negative effect on the neurogenic niche development in postnatal offspring.

  10. Maternal Forced Swimming Reduces Cell Proliferation in the Postnatal Dentate Gyrus of Mouse Offspring

    PubMed Central

    Wasinski, Frederick; Estrela, Gabriel R.; Arakaki, Aline M.; Bader, Michael; Alenina, Natalia; Klempin, Friederike; Araújo, Ronaldo C.

    2016-01-01

    Physical exercise positively affects the metabolism and induces proliferation of precursor cells in the adult brain. Maternal exercise likewise provokes adaptations early in the offspring. Using a high-intensity swimming protocol that comprises forced swim training before and during pregnancy, we determined the effect of maternal swimming on the mouse offspring's neurogenesis. Our data demonstrate decreased proliferation in sublayers of the postnatal dentate gyrus in offspring of swimming mother at postnatal day (P) 8 accompanied with decreased survival of newly generated cells 4 weeks later. The reduction in cell numbers was predominantly seen in the hilus and molecular layer. At P35, the reduced amount of cells was also reflected by a decrease in the population of newly generated immature and mature neurons of the granule cell layer. Our data suggest that forced maternal swimming at high-intensity has a negative effect on the neurogenic niche development in postnatal offspring. PMID:27621701

  11. Maternal Forced Swimming Reduces Cell Proliferation in the Postnatal Dentate Gyrus of Mouse Offspring.

    PubMed

    Wasinski, Frederick; Estrela, Gabriel R; Arakaki, Aline M; Bader, Michael; Alenina, Natalia; Klempin, Friederike; Araújo, Ronaldo C

    2016-01-01

    Physical exercise positively affects the metabolism and induces proliferation of precursor cells in the adult brain. Maternal exercise likewise provokes adaptations early in the offspring. Using a high-intensity swimming protocol that comprises forced swim training before and during pregnancy, we determined the effect of maternal swimming on the mouse offspring's neurogenesis. Our data demonstrate decreased proliferation in sublayers of the postnatal dentate gyrus in offspring of swimming mother at postnatal day (P) 8 accompanied with decreased survival of newly generated cells 4 weeks later. The reduction in cell numbers was predominantly seen in the hilus and molecular layer. At P35, the reduced amount of cells was also reflected by a decrease in the population of newly generated immature and mature neurons of the granule cell layer. Our data suggest that forced maternal swimming at high-intensity has a negative effect on the neurogenic niche development in postnatal offspring. PMID:27621701

  12. Possible contributory role of the central histaminergic system in the forced swimming model.

    PubMed

    Noguchi, S; Fukuda, Y; Inukai, T

    1992-05-01

    Forced swimming is considered to bring about a depressive or despair state in experimental animals, usually manifested as immobility. Levoprotiline (CAS 76496-68-9), a new antidepressant, clearly reduced the duration of immobility in the forced swimming model in mice. As levoprotiline does not inhibit noradrenaline or serotonin reuptake, this effect did not seem to have been brought about through central monoaminergic systems. Histamine and tele-methylhistamine levels, the main metabolite of histamine in the cerebral cortex, were found to be significantly increased in the forced swimming model. Since the only significant known effect of levoprotiline on the neurotransmitter system is its histamine H1 receptor antagonism, a possible contribution of the central histaminergic system to the forced swimming model is proposed. The action of mepyramine, a histamine H1 receptor antagonist in reducing the duration of immobility seemed to support this proposition. It should be noted that antihistaminergic properties are shared by many antidepressant drugs.

  13. A proposal for refining the forced swim test in Swiss mice.

    PubMed

    Costa, Ana Paula Ramos; Vieira, Cintia; Bohner, Lauren O L; Silva, Cristiane Felisbino; Santos, Evelyn Cristina da Silva; De Lima, Thereza Christina Monteiro; Lino-de-Oliveira, Cilene

    2013-08-01

    The forced swim test (FST) is a preclinical test to the screening of antidepressants based on rats or mice behaviours, which is also sensitive to stimulants of motor activity. This work standardised and validated a method to register the active and passive behaviours of Swiss mice during the FST in order to strength the specificity of the test. Adult male Swiss mice were subjected to the FST for 6 min without any treatment or after intraperitoneal injection of saline (0.1 ml/10 g), antidepressants (imipramine, desipramine, or fluoxetine, 30 mg/kg) or stimulants (caffeine, 30 mg/kg or apomorphine, 10mg/kg). The latency, frequency and duration of behaviours (immobility, swimming, and climbing) were scored and summarised in bins of 6, 4, 2 or 1 min. Parameters were first analysed using Principal Components Analysis generating components putatively related to antidepressant (first and second) or to stimulant effects (third). Antidepressants and stimulants affected similarly the parameters grouped into all components. Effects of stimulants on climbing were better distinguished of antidepressants when analysed during the last 4 min of the FST. Surprisingly, the effects of antidepressants on immobility were better distinguished from saline when parameters were scored in the first 2 min. The method proposed here is able to distinguish antidepressants from stimulants of motor activity using Swiss mice in the FST. This refinement should reduce the number of mice used in preclinical evaluation of antidepressants.

  14. Forced swimming and imipramine modify plasma and brain amino acid concentrations in mice.

    PubMed

    Murakami, Tatsuro; Yamane, Haruka; Tomonaga, Shozo; Furuse, Mitsuhiro

    2009-01-01

    The relationships between monoamine metabolism and forced swimming or antidepressants have been well studied, however information is lacking regarding amino acid metabolism under these conditions. Therefore, the aim of the present study was to investigate the effects of forced swimming and imipramine on amino acid concentrations in plasma, the cerebral cortex and the hypothalamus in mice. Forced swimming caused cerebral cortex concentrations of L-glutamine, L-alanine, and taurine to be increased, while imipramine treatment caused decreased concentrations of L-glutamate, L-alanine, L-tyrosine, L-methionine, and L-ornithine. In the hypothalamus, forced swimming decreased the concentration of L-serine while imipramine treatment caused increased concentration of beta-alanine. Forced swimming caused increased plasma concentration of taurine, while concentrations of L-serine, L-asparagine, L-glutamine and beta-alanine were decreased. Imipramine treatment caused increased plasma concentration of all amino acid, except for L-aspartate and taurine. In conclusion, forced swimming and imipramine treatment modify central and peripheral amino acid metabolism. These results may aid in the identification of amino acids that have antidepressant-like effects, or may help to refine the dosages of antidepressant drugs. PMID:19010319

  15. Sex and age differences in the impact of the forced swimming test on the levels of steroid hormones.

    PubMed

    Martínez-Mota, Lucía; Ulloa, Rosa-Elena; Herrera-Pérez, Jaime; Chavira, Roberto; Fernández-Guasti, Alonso

    2011-10-24

    Compared with the adult disorder, depression in children exhibits differences in its neurobiology, particularly in the HPA axis regulation. The bases of such differences can be evaluated in animal models of depression. The objective of the present study was to determine age and sex differences of Wistar rats in the forced swimming test (FST). The influence of sex and age on corticosterone, estrogens and testosterone serum levels was also determined. Prepubertal rats showed immobility, swimming and climbing behaviors during the pre-test and test sessions. In addition, in the prepubertal animals, no sex differences were found during the pre-test and test sessions. Age comparisons indicated no differences in the female groups, however adult males exhibited more immobility and less swimming than young males, in both FST sessions. The young and female rats showed less immobility behavior and increased levels of estrogens after the FST. The present results indicate that the FST is an animal model suitable to evaluate depressive-like behaviors in prepubertal subjects and to explore behavioral changes related to neurodevelopment.

  16. Force-free swimming of a model helical flagellum in viscoelastic fluids

    PubMed Central

    Liu, Bin; Powers, Thomas R.; Breuer, Kenneth S.

    2011-01-01

    We precisely measure the force-free swimming speed of a rotating helix in viscous and viscoelastic fluids. The fluids are highly viscous to replicate the low Reynolds number environment of microorganisms. The helix, a macroscopic scale model for the bacterial flagellar filament, is rigid and rotated at a constant rate while simultaneously translated along its axis. By adjusting the translation speed to make the net hydrodynamic force vanish, we measure the force-free swimming speed as a function of helix rotation rate, helix geometry, and fluid properties. We compare our measurements of the force-free swimming speed of a helix in a high-molecular weight silicone oil with predictions for the swimming speed in a Newtonian fluid, calculated using slender-body theories and a boundary-element method. The excellent agreement between theory and experiment in the Newtonian case verifies the high accuracy of our experiments. For the viscoelastic fluid, we use a polymer solution of polyisobutylene dissolved in polybutene. This solution is a Boger fluid, a viscoselastic fluid with a shear-rate-independent viscosity. The elasticity is dominated by a single relaxation time. When the relaxation time is short compared to the rotation period, the viscoelastic swimming speed is close to the viscous swimming speed. As the relaxation time increases, the viscoelastic swimming speed increases relative to the viscous speed, reaching a peak when the relaxation time is comparable to the rotation period. As the relaxation time is further increased, the viscoelastic swimming speed decreases and eventually falls below the viscous swimming speed. PMID:22106263

  17. The involvement of serotonergic system in the antidepressant effect of zinc in the forced swim test.

    PubMed

    Szewczyk, Bernadeta; Poleszak, Ewa; Wlaź, Piotr; Wróbel, Andrzej; Blicharska, Eliza; Cichy, Agnieszka; Dybała, Małgorzata; Siwek, Agata; Pomierny-Chamioło, Lucyna; Piotrowska, Anna; Brański, Piotr; Pilc, Andrzej; Nowak, Gabriel

    2009-03-17

    Recent preclinical data indicated the antidepressant-like activity of zinc in different tests and models of depression. The present study investigates the involvement of the serotonergic system in zinc activity in the forced swim test (FST) in mice and rats. The combined treatment of sub-effective doses of zinc (hydroaspartate, 2.5 mg Zn/kg) and citalopram (15 mg/kg), fluoxetine (5 mg/kg) but not with reboxetine (2.5 mg/kg) significantly reduces the immobility time in the FST in mice. These treatments had no influence on the spontaneous locomotor activity. Moreover, while the antidepressant-like effect of zinc (5 mg/kg) in the FST was significantly blocked by pretreatment with inhibitor of serotonin synthesis, p-chlorophenylalanine (pCPA, 3x200 mg/kg), 5HT-2(A/C) receptor antagonist, ritanserin (4 mg/kg) or 5HT-1A receptor antagonist, WAY 1006335 (0.1 mg/kg), the zinc-induced reduction in the locomotor activity was not affected by these serotonin modulator agents. These results indicate the specific involvement of the serotonergic system in antidepressant but not the motion behavior of zinc in mice. Also, an increase in the swimming but not climbing parameter of the rat FST observed following zinc administration (2.5 and 5 mg Zn/kg) indicates the serotonin pathway participation. This present data indicates that the antidepressant-like activity of zinc observed in the FST involves interaction with the serotonergic system.

  18. Effect of acute imipramine administration on the pattern of forced swim-induced c-Fos expression in the mouse brain.

    PubMed

    Yanagida, Satoru; Motomura, Keisuke; Ohashi, Ayako; Hiraoka, Kentaro; Miura, Tomofumi; Kanba, Shigenobu

    2016-08-26

    The forced swim test (FST) has been widely used for the preclinical evaluation of antidepressant drugs. Despite considerable differences in the protocol, equivalence of the FST for rats and mice has been rarely questioned. Previous research on the FST for rats revealed that repeated administration of antidepressant drugs attenuates the c-Fos response to swim stress in the hypothalamus and limbic regions. However, few studies have made similar investigations using the FST for mice. In the present study, we explored the mouse brain through immunohistochemistry staining for c-Fos after acute administration of imipramine or saline with or without a subsequent swim session. Imipramine enhanced the c-Fos density in regions of the central extended amygdala, while forced swim stress increased c-Fos expression in some hypothalamic (the ventrolateral preoptic nucleus and dorsomedial nucleus) and brain stem regions, which is consistent with previous reports. In contrast to previous literature with rats, swim stress brought a significant increase in c-Fos expression in the lateral septal nucleus and some other regions in the hypothalamus (the intermediate hypothalamic area, the paraventricular and arcuate nucleus) only in the imipramine-pretreated group, which has not been observed previously. In the arcuate nucleus, double immunostaining revealed that c-Fos was rarely co-expressed with proopiomelanocortin or tyrosine hydroxylase regardless of imipramine treatment. The present results suggest that the activation of several regions in the lateral septum and the hypothalamus underlies antidepressant-like effect in the mouse FST. PMID:27373591

  19. Chromatin alterations in response to forced swimming underlie increased prodynorphin transcription.

    PubMed

    Reed, B; Fang, N; Mayer-Blackwell, B; Chen, S; Yuferov, V; Zhou, Y; Kreek, M J

    2012-09-18

    Antagonism of the kappa opioid receptor (KOR) has been reported to have anti-depressant-like properties. The dynorphin/KOR system is a crucial neurochemical substrate underlying the pathologies of addictive diseases, affective disorders and other disease states. However, the molecular underpinnings and neuroanatomical localization of the dysregulation of this system have not yet been fully elucidated. Utilizing the Porsolt Forced Swim Test (FST), an acute stressor commonly used as in rodent models measuring antidepressant efficacy, male Sprague-Dawley rats were subject to forced swimming for 15 min, treated 1h with vehicle or norbinaltorphimine (nor-BNI) (5 or 10mg/kg), and then 1 day later subject to FST for 5 min. In accordance with previous findings, nor-BNI dose dependently increased climbing time and reduced immobility. In comparison to control animals not exposed to FST, we observed a significant elevation in prodynorphin (pDyn) mRNA levels following FST using real-time optical polymerase chain reaction (PCR) in the caudate putamen but not in the nucleus accumbens, hypothalamus, amygdala, frontal cortex, or hippocampus. nor-BNI treatment did not affect pDyn mRNA levels in comparison to animals that received vehicle. The corresponding brain regions from the opposite hemisphere were analyzed for underlying chromatin modifications of the prodynorphin gene promoter region using chromatin immunoprecipitation with antibodies against specifically methylated histones H3K27Me2, H3K27Me3, H3K4Me2, and H3K4Me3, as well as CREB-1 and MeCP2. Significant alterations in proteins bound to DNA in the Cre-3, Cre-4, and Sp1 regions of the prodynorphin promoter were found in the caudate putamen of the FST saline-treated animals compared to control animals, with no changes observed in the hippocampus. Epigenetic changes resulting in elevated dynorphin levels specifically in the caudate putamen may in part underlie the enduring effects of stress.

  20. Chromatin Alterations in Response to Forced Swimming Underlie Increased Prodynorphin Transcription

    PubMed Central

    Reed, Brian; Fang, Nancy; Blackwell-Mayer, Brandan; Chen, Shasha; Yuferov, Vadim; Zhou, Yan; Kreek, Mary Jeanne

    2012-01-01

    Antagonism of the kappa opioid receptor (KOR) has been reported to have anti-depressant-like properties. The dynorphin/KOR system is a crucial neurochemical substrate underlying the pathologies of addictive diseases, affective disorders and other disease states. However, the molecular underpinnings and neuroanatomical localization of the dysregulation of this system have not yet been fully elucidated. Utilizing the Porsolt Forced Swim Test (FST), an acute stressor commonly used as in rodent models measuring antidepressant efficacy, male Sprague-Dawley rats were subject to forced swimming for 15 minutes, treated 1 hour with vehicle or nor-BNI (5 or 10 mg/kg), and then 1 day later subject to FST for five minutes. In accordance with previous findings, nor-BNI dose dependently increased climbing time and reduced immobility. In comparison to control animals not exposed to FST, we observed a significant elevation in prodynorphin (pDyn) mRNA levels following FST using real-time optical PCR in the caudate putamen but not in the nucleus accumbens, hypothalamus, amygdala, frontal cortex, or hippocampus. Nor-BNI treatment did not affect pDyn mRNA levels in comparison to animals that received vehicle. The corresponding brain regions from the opposite hemisphere were analyzed for underlying chromatin modifications of the prodynorphin gene promoter region using chromatin immunoprecipitation with antibodies against specifically methylated histones H3K27Me2, H3K27Me3, H3K4Me2, and H3K4Me3, as well as CREB-1 and MeCP2. Significant alterations in proteins bound to DNA in the Cre-3, Cre-4, and Sp1 regions of the prodynorphin promoter were found in the caudate putamen of the FST saline-treated animals compared to control animals, with no changes observed in the hippocampus. Epigenetic changes resulting in elevated dynorphin levels specifically in the caudate putamen may in part underlie the enduring effects of stress. PMID:22698692

  1. Effect of swimming on the production of aldosterone in rats.

    PubMed

    Lieu, Fu-Kong; Lin, Chih-Yung; Wang, Paulus S; Jian, Cai-Yun; Yeh, Yung-Hsing; Chen, Yi-An; Wang, Kai-Lee; Lin, Yi-Chun; Chang, Ling-Ling; Wang, Guei-Jane; Wang, Shyi-Wu

    2014-01-01

    It has been demonstrated that exercise is one of the stresses known to increase the aldosterone secretion. Both potassium and angiotensin II (Ang II) levels are shown to be correlated with aldosterone production during exercise, but the mechanism is still unclear. In an in vivo study, male rats were catheterized via right jugular vein (RJV), and divided into four groups namely water immersion, swimming, lactate infusion (13 mg/kg/min) and pyruvate infusion (13 mg/kg/min) groups. Each group was treated for 10 min. Blood samples were collected at 0, 10, 15, 30, 60 and 120 min from RJV after administration. In an in vitro study, rat zona glomerulosa (ZG) cells were challenged by lactate (1-10 mM) in the presence or absence of Ang II (10(-8) M) for 60 min. The levels of aldosterone in plasma and medium were measured by radioimmunoassay. Cell lysates were analyzed by immunoblotting assay. After exercise and lactate infusion, plasma levels of aldosterone and lactate were significantly higher than those in the control group. Swimming for 10 min significantly increased the plasma Ang II levels in male rats. Administration of lactate plus Ang II significantly increased aldosterone production and enhanced protein expression of steroidogenic acute regulatory protein (StAR) in ZG cells. These results demonstrated that acute exercise led to the increase of both aldosterone and Ang II secretion, which is associated with lactate action on ZG cells and might be dependent on the activity of renin-angiotensin system. PMID:25289701

  2. Effect of Swimming on the Production of Aldosterone in Rats

    PubMed Central

    Wang, Paulus S.; Jian, Cai-Yun; Yeh, Yung-Hsing; Chen, Yi-An; Wang, Kai-Lee; Lin, Yi-Chun; Chang, Ling-Ling; Wang, Guei-Jane; Wang, Shyi-Wu

    2014-01-01

    It has been demonstrated that exercise is one of the stresses known to increase the aldosterone secretion. Both potassium and angiotensin II (Ang II) levels are shown to be correlated with aldosterone production during exercise, but the mechanism is still unclear. In an in vivo study, male rats were catheterized via right jugular vein (RJV), and divided into four groups namely water immersion, swimming, lactate infusion (13 mg/kg/min) and pyruvate infusion (13 mg/kg/min) groups. Each group was treated for 10 min. Blood samples were collected at 0, 10, 15, 30, 60 and 120 min from RJV after administration. In an in vitro study, rat zona glomerulosa (ZG) cells were challenged by lactate (1–10 mM) in the presence or absence of Ang II (10−8 M) for 60 min. The levels of aldosterone in plasma and medium were measured by radioimmunoassay. Cell lysates were analyzed by immunoblotting assay. After exercise and lactate infusion, plasma levels of aldosterone and lactate were significantly higher than those in the control group. Swimming for 10 min significantly increased the plasma Ang II levels in male rats. Administration of lactate plus Ang II significantly increased aldosterone production and enhanced protein expression of steroidogenic acute regulatory protein (StAR) in ZG cells. These results demonstrated that acute exercise led to the increase of both aldosterone and Ang II secretion, which is associated with lactate action on ZG cells and might be dependent on the activity of renin-angiotensin system. PMID:25289701

  3. Impact of water temperature and stressor controllability on swim stress-induced changes in body temperature, serum corticosterone, and immobility in rats.

    PubMed

    Drugan, Robert C; Eren, Senem; Hazi, Agnes; Silva, Jennifer; Christianson, John P; Kent, Stephen

    2005-10-01

    The present study compared the effects of three different water temperatures (20, 25, and 30 degrees C) and stressor controllability on several physiological and behavioral endpoints in an intermittent swim stress paradigm. The escape latency of rats in the 20 and 25 degrees C water was less than that observed for the 30 degrees C group. Both escape and yoked groups at 20 and 25 degrees C exhibited moderate to severe hypothermia following the swim stress session that returned to prestress levels 30-40 min post-stress. At 30 degrees C core body temperature (Tb) only decreased by 1 degree C for either swim group. Following swim, serum corticosterone (CORT) levels were significantly elevated in both escape and yoked groups in comparison to confined and home cage controls. The confined control group showed a significant elevation that was approximately halfway between the home cage control and the swim stress groups. At 30 degrees C, there was still a significant elevation of serum CORT in both swim groups in comparison to confined and home cage controls. Therefore, 30 degrees C appears to be the optimal water temperature to evaluate stress controllability effects in the current paradigm. In a final experiment, swim stressor controllability effects were examined in a 5 min forced swim test (FST) 24 h following the initial stress exposure. Rats exposed to yoked-inescapable swim stress at 30 degrees C exhibited more immobility than their escapable swim stress and confined counterparts, while the escape and confined controls did not differ. These results demonstrate that the behavioral deficits observed in the FST are attributable to the stress of inescapable swim and not swim stress per se.

  4. A biomechanical review of the techniques used to estimate or measure resistive forces in swimming.

    PubMed

    Sacilotto, Gina B D; Ball, Nick; Mason, Bruce R

    2014-02-01

    Resistive or drag forces encountered during free swimming greatly influence the swim performance of elite competitive swimmers. The benefits in understanding the factors which affect the drag encountered will enhance performance within the sport. However, the current techniques used to experimentally measure or estimate drag values are questioned for their consistency, therefore limiting investigations in these factors. This paper aims to further understand how the resistive forces in swimming are measured and calculated. All techniques outlined demonstrate both strengths and weaknesses in the overall assessment of free swimming. By reviewing all techniques in this area, the reader should be able to select which one is best depending on what researchers want to gain from the testing.

  5. Physical Forces Shape Group Identity of Swimming Pseudomonas putida Cells

    PubMed Central

    Espeso, David R.; Martínez-García, Esteban; de Lorenzo, Víctor; Goñi-Moreno, Ángel

    2016-01-01

    The often striking macroscopic patterns developed by motile bacterial populations on agar plates are a consequence of the environmental conditions where the cells grow and spread. Parameters such as medium stiffness and nutrient concentration have been reported to alter cell swimming behavior, while mutual interactions among populations shape collective patterns. One commonly observed occurrence is the mutual inhibition of clonal bacteria when moving toward each other, which results in a distinct halt at a finite distance on the agar matrix before having direct contact. The dynamics behind this phenomenon (i.e., intolerance to mix in time and space with otherwise identical others) has been traditionally explained in terms of cell-to-cell competition/cooperation regarding nutrient availability. In this work, the same scenario has been revisited from an alternative perspective: the effect of the physical mechanics that frame the process, in particular the consequences of collisions between moving bacteria and the semi-solid matrix of the swimming medium. To this end, we set up a simple experimental system in which the swimming patterns of Pseudomonas putida were tested with different geometries and agar concentrations. A computational analysis framework that highlights cell-to-medium interactions was developed to fit experimental observations. Simulated outputs suggested that the medium is compressed in the direction of the bacterial front motion. This phenomenon generates what was termed a compression wave that goes through the medium preceding the swimming population and that determines the visible high-level pattern. Taken together, the data suggested that the mechanical effects of the bacteria moving through the medium created a factual barrier that impedes to merge with neighboring cells swimming from a different site. The resulting divide between otherwise clonal bacteria is thus brought about by physical forces—not genetic or metabolic programs. PMID

  6. Physical Forces Shape Group Identity of Swimming Pseudomonas putida Cells

    PubMed Central

    Espeso, David R.; Martínez-García, Esteban; de Lorenzo, Víctor; Goñi-Moreno, Ángel

    2016-01-01

    The often striking macroscopic patterns developed by motile bacterial populations on agar plates are a consequence of the environmental conditions where the cells grow and spread. Parameters such as medium stiffness and nutrient concentration have been reported to alter cell swimming behavior, while mutual interactions among populations shape collective patterns. One commonly observed occurrence is the mutual inhibition of clonal bacteria when moving toward each other, which results in a distinct halt at a finite distance on the agar matrix before having direct contact. The dynamics behind this phenomenon (i.e., intolerance to mix in time and space with otherwise identical others) has been traditionally explained in terms of cell-to-cell competition/cooperation regarding nutrient availability. In this work, the same scenario has been revisited from an alternative perspective: the effect of the physical mechanics that frame the process, in particular the consequences of collisions between moving bacteria and the semi-solid matrix of the swimming medium. To this end, we set up a simple experimental system in which the swimming patterns of Pseudomonas putida were tested with different geometries and agar concentrations. A computational analysis framework that highlights cell-to-medium interactions was developed to fit experimental observations. Simulated outputs suggested that the medium is compressed in the direction of the bacterial front motion. This phenomenon generates what was termed a compression wave that goes through the medium preceding the swimming population and that determines the visible high-level pattern. Taken together, the data suggested that the mechanical effects of the bacteria moving through the medium created a factual barrier that impedes to merge with neighboring cells swimming from a different site. The resulting divide between otherwise clonal bacteria is thus brought about by physical forces—not genetic or metabolic programs.

  7. Do stress hormones connect environmental effects with behavior in the forced swim test?

    PubMed

    Pintér, Ottó; Domokos, Ágnes; Mergl, Zsuzsa; Mikics, Éva; Zelena, Dóra

    2011-01-01

    Forced swim test (FST) is a widely used test for antidepressant development. Depression is a stress related disease, as hormones of the stress-axis can modify mood. However it is not clear, how the appearance of depressive-like behavior (floating) in FST is connected with changes in the stress-hormone levels. We hypothesized, that different manipulations would alter the behavior through changes in stress-hormone levels. First the effect of environmental alterations was studied. Increasing water-temperature enhanced floating time together with a decrease in adrenocorticotropin levels. During the dark phase of the day rats spent more time with floating independently from the actual lighting. Neither the phase nor the actual lighting had significant effect on adrenocorticotropin concentrations with higher corticosterone levels during the dark phase. At greater water depth rats float less but the size of animals had no effect. Water depth did not influence adrenocorticotropin and corticosterone responses, but the size of the rats significantly affected both factors. Secondly, administration of imipramine reduced floating and adrenocorticotropin level without affecting corticosterone. Despite the known connection between depression and stress we did not find a correlation between floating behavior and hormone levels. As an alternative mechanism imipramine-induced heart rate and core body temperature decrease was found by telemetric approach. This study is the first summary in rats examining the effect of wide range of environmental alterations during FST. It seems likely that both brain monoamines and stress-axis take part in the development of depression, but these pathways are regulated independently.

  8. Do stress hormones connect environmental effects with behavior in the forced swim test?

    PubMed

    Pintér, Ottó; Domokos, Ágnes; Mergl, Zsuzsa; Mikics, Éva; Zelena, Dóra

    2011-01-01

    Forced swim test (FST) is a widely used test for antidepressant development. Depression is a stress related disease, as hormones of the stress-axis can modify mood. However it is not clear, how the appearance of depressive-like behavior (floating) in FST is connected with changes in the stress-hormone levels. We hypothesized, that different manipulations would alter the behavior through changes in stress-hormone levels. First the effect of environmental alterations was studied. Increasing water-temperature enhanced floating time together with a decrease in adrenocorticotropin levels. During the dark phase of the day rats spent more time with floating independently from the actual lighting. Neither the phase nor the actual lighting had significant effect on adrenocorticotropin concentrations with higher corticosterone levels during the dark phase. At greater water depth rats float less but the size of animals had no effect. Water depth did not influence adrenocorticotropin and corticosterone responses, but the size of the rats significantly affected both factors. Secondly, administration of imipramine reduced floating and adrenocorticotropin level without affecting corticosterone. Despite the known connection between depression and stress we did not find a correlation between floating behavior and hormone levels. As an alternative mechanism imipramine-induced heart rate and core body temperature decrease was found by telemetric approach. This study is the first summary in rats examining the effect of wide range of environmental alterations during FST. It seems likely that both brain monoamines and stress-axis take part in the development of depression, but these pathways are regulated independently. PMID:21505269

  9. Clarification of Unsteady Fluid Forces Acting on Limbs in Swimming Using an Underwater Robot Arm

    NASA Astrophysics Data System (ADS)

    Nakashima, Motomu; Takahashi, Akemi

    The objective of this study was to clarify the unsteady characteristics of the fluid force acting on limbs during swimming. For this objective, an underwater robot arm, which has five degrees-of-freedom in order to perform the various complicated limb motions during swimming, was developed. In the previous study, an experiment to measure the unsteady fluid force was conducted for four swimming strokes of the upper and lower limbs. In this paper, the unsteady fluid force model was firstly formulated. Second, the simulation of experimental conditions was conducted. Two fluid force coefficients, which are the parameters in the fluid force model, were identified using optimizing calculation, so that the discrepancies of the forces and moments between the experiment and simulation were minimized. In addition, fluid force models which are dependant only on the limbs’ shapes were determined. Good agreement between the experiment and simulation with the determined fluid force model indicated the validity of the determined model. The identified fluid model will be useful for mechanical analyses of various swimming motions in future studies.

  10. Intermittent cold water swim stress increases immobility and interferes with escape performance in rat.

    PubMed

    Christianson, John P; Drugan, Robert C

    2005-11-30

    The behavioral consequences of intermittent, 5 s cold-water swims (15 degrees C) or confinement were assessed 24 h after stress in a 5 min forced swim test or an instrumental swim escape test (SET). The SET was conducted with temporal and instrumental parameters similar to the shock-motivated shuttle escape test. The tests detected significantly increased immobility in the forced swim test and increased latency to escape in the SET. These results extend previous findings with intermittent swim stress and provide evidence that intermittent swim stress produces behavioral deficits similar to other stress models. This new model may be a useful tool for exploring the physiological mechanisms underlying the stress response.

  11. Effects of corticosterone on response consolidation and retrieval in the forced swim test.

    PubMed

    Mitchell, J B; Meaney, M J

    1991-12-01

    In the forced swimming test, adrenal hormones regulate immobility time during a test swim given 24 hr after the initial training swim (e.g., the deficit in adrenalectomized animals is reduced when animals are given corticosterone [B] immediately after the training session). In this study, adrenalectomy decreased and B restored immobility during the test swims. The effects of adrenalectomy were completely reversed by 1 mg/kg doses of B, which results in plasma B levels that are comparable to values under basal resting conditions. Higher doses of B had no further effect. B given before or immediately after training partially reversed the effects of adrenalectomy. The complete reversal of the effects of adrenalectomy, however, required the presence of B during both training and testing, suggesting that B plays a role in the consolidation-retention and retrieval of the immobility response.

  12. Immobility in the forced swim test is adaptive and does not reflect depression.

    PubMed

    Molendijk, Marc L; de Kloet, E Ronald

    2015-12-01

    The forced swim test is based on the progressive immobility a rodent displays when immersed in a beaker filled with water from where no escape is possible. While the test was originally designed to identify the antidepressant potential of drugs, over the past decade a rapidly growing number of publications (more than 2000) portray this immobility response anthropomorphically as a measure for depression and despair. This is incorrect. The response to the forced swim stressor should be considered for what it shows: a switch from active to passive behavior in the face of an acute stressor, aligned to cognitive functions underlying behavioral adaptation and survival.

  13. Oxidative stress status and placental implications in diabetic rats undergoing swimming exercise after embryonic implantation.

    PubMed

    Volpato, Gustavo Tadeu; Damasceno, Débora Cristina; Sinzato, Yuri Karen; Ribeiro, Viviane Maria; Rudge, Marilza Vieira Cunha; Calderon, Iracema Mattos Paranhos

    2015-05-01

    The potential benefits and risks of physical exercise on fetal development during pregnancy remain unclear. The aim was to analyze maternal oxidative stress status and the placental morphometry to relate to intrauterine growth restriction (IUGR) from diabetic female rats submitted to swimming program after embryonic implantation. Pregnant Wistar rats were distributed into 4 groups (11 animals/group): control-nondiabetic sedentary rats, control exercised-nondiabetic exercised rats, diabetic-diabetic sedentary rats, and diabetic exercised-diabetic exercised rats. A swimming program was used as an exercise model. At the end of pregnancy, the maternal oxidative stress status, placental morphology, and fetal weight were analyzed. The swimming program was not efficient to reduce the hyperglycemia-induced oxidative stress. This fact impaired placental development, resulting in altered blood flow and energy reserves, which contributed to a deficient exchange of nutrients and oxygen for the fetal development, leading to IUGR. PMID:25361551

  14. Oxidative Stress Status and Placental Implications in Diabetic Rats Undergoing Swimming Exercise After Embryonic Implantation

    PubMed Central

    Damasceno, Débora Cristina; Sinzato, Yuri Karen; Ribeiro, Viviane Maria; Rudge, Marilza Vieira Cunha; Calderon, Iracema Mattos Paranhos

    2015-01-01

    The potential benefits and risks of physical exercise on fetal development during pregnancy remain unclear. The aim was to analyze maternal oxidative stress status and the placental morphometry to relate to intrauterine growth restriction (IUGR) from diabetic female rats submitted to swimming program after embryonic implantation. Pregnant Wistar rats were distributed into 4 groups (11 animals/group): control—nondiabetic sedentary rats, control exercised—nondiabetic exercised rats, diabetic—diabetic sedentary rats, and diabetic exercised—diabetic exercised rats. A swimming program was used as an exercise model. At the end of pregnancy, the maternal oxidative stress status, placental morphology, and fetal weight were analyzed. The swimming program was not efficient to reduce the hyperglycemia-induced oxidative stress. This fact impaired placental development, resulting in altered blood flow and energy reserves, which contributed to a deficient exchange of nutrients and oxygen for the fetal development, leading to IUGR. PMID:25361551

  15. Simultaneous impairment of passive avoidance learning and nociception in rats following chronic swim stress

    PubMed Central

    Nazeri, Masoud; Shabani, Mohammad; Parsania, Shahrnaz; Golchin, Leila; Razavinasab, Moazamehosadat; Abareghi, Fatemeh; Kermani, Moein

    2016-01-01

    Background: Stress can alter response to nociception. Under certain circumstances stress enhances nociception, a phenomenon which is called stress-induced hyperalgesia (SIH). While nociception has been studied in this paradigm, possible alterations occurring in passive avoidance (PA) learning after exposing rats to this type of stress has not been studied before. Materials and Methods: In the current study, we evaluated the effect of chronic swim stress (FS) or sham swim (SS) on nociception in both spinal (tail-flick) and supraspinal (53.5°C hot-pate) levels. Furthermore, PA task was performed to see whether chronic swim stress changes PA learning or not. Mobility of rats and anxiety-like behavior were assessed using open-field test (OFT). Results: Supraspinal pain response was altered by swim stress (hot-plate test). PA learning was impaired by swim stress, rats in SS group did not show such impairments. Rats in the FS group showed increased mobility (rearing, velocity, total distant moved (TDM) and decreased anxiety-like behavior (time spent in center and grooming) compared to SS rats. Conclusions: This study demonstrated the simultaneous impairment of PA and nociception under chronic swim stress, whether this is simply a co-occurrence or not is of special interest. This finding may implicate a possible role for limbic structures, though this hypothesis should be studied by experimental lesions in different areas of rat brain to assess their possible role in the pathophysiology of SIH. PMID:27308265

  16. Hepatoprotective Effects of Swimming Exercise against D-Galactose-Induced Senescence Rat Model

    PubMed Central

    Chiang, Wen-Dee; Huang, Wen-Ching; Huang, Chih-Yang; Hsu, Mei-Chich; Lin, Wan-Teng

    2013-01-01

    This study investigates whether a 12-week swimming exercise training can prevent liver damage or senescence associated biomarkers in an experimental aging model in rats. Twenty-three male Sprague-Dawley rats were divided into four groups: vehicle treatment with sedentary control (C, n = 6), aging induction with sedentary (A, n = 6), vehicle treatment with swimming exercise (SW, n = 5), and aging induction with swimming exercise (A + SW, n = 6). Rats in groups A and AS received intraperitoneal d-galactose injections (150 mg/kg/day) for 12 weeks to induce aging. Rats in groups SW and A + SW were subjected to swimming exercise training for 12 weeks. Body weight, liver weight, epididymal fat mass, blood biochemistry, and liver pathology were performed at the end of the experiment. Hepatic senescence protein markers such as β-galactosidase, p53, and p21, as well as the inflammatory mediator, IL-6, were examined. The d-galactose-treated rats exhibited increases in AST and γ-GT plasma levels and β-galactosidase protein expression compared to the control group. Swimming exercise significantly reduced BW, epididymal fat mass, γ-GT activity, and p53, p21, and IL-6 protein levels compared to the aging group. These results suggest that a 12-week swimming exercise program suppresses senescence markers and downregulates inflammatory mediator in the liver tissues of d-galactose-induced aging rats. PMID:23843869

  17. Clarification of Unsteady Fluid Forces Acting on Limbs in Swimming Using an Underwater Robot Arm

    NASA Astrophysics Data System (ADS)

    Nakashima, Motomu; Takahashi, Akemi

    The objective of this study was to clarify the unsteady characteristics of the fluid forces acting on limbs during swimming. For this objective, an underwater robot arm was developed in this paper. The robot arm has five degrees-of-freedom in order to perform the various complicated limb motions during swimming. In addition, by changing the hand replica into the foot one, the robot also can perform the lower limb motions. The joint torques and the resultant thrust can be measured by the force sensors attached to the robot. In a circulating water tank, an experiment to measure the fluid forces was conducted for four swimming strokes of the upper and lower limbs. From the experiment, it was found that even the slight difference of the fluid forces between slightly different swimming motions can be quantified by the developed experimental system. In addition, it was suggested that ‘nipping’ the water by both lower limbs during the kick of the breaststroke almost does not affect thrust generation. The developed experimental system with the robot arm is useful not only for measuring the unsteady fluid forces, but also for flow visualization in future studies.

  18. Impact of maternal melatonin suppression on forced swim and tail suspension behavioral despair tests in adult offspring

    PubMed Central

    Voiculescu, SE; Rosca, AE; Zeca, V; Zagrean, L; Zagrean, AM

    2015-01-01

    Melatonin is an essential hormone, which regulates circadian rhythms and has antioxidative and anticarcinogenic effects. As melatonin secretion is suppressed by light, this effect was examined on the offspring of the Wistar rat females exposed to continuous light (500 lux) during the second half of the pregnancy (day 12 to 21). Control rats were kept under a 12:12 light-dark cycle. The resulted male offspring have been behaviorally assessed for depression after postnatal day 60 by using Forced Swim Test (FST) and Tail Suspension Test (TST). Animals resulted from the melatonin deprived pregnancies have developed an abnormal response in the TST, but a normal FST behavior. Also, TST active movement was different in the melatonin suppression group compared to the control group. These findings suggest that intrauterine melatonin deprivation might be linked to the depressive like behavior in adult male offspring. PMID:25866579

  19. Antidepressant-like properties of prepro-TRH 178-199: acute effects in the forced swim test.

    PubMed

    Redei, E; Organ, M; Hart, S

    1999-11-01

    This study examined the central effects of rat prepro-TRH 178-199, a peptide with corticotropin release inhibiting activity at the pituitary, on the Porsolt forced swim test (FST) of depressive behavior in rats. Subacute intracerebroventricular administration of prepro-TRH 178-199 dose-responsively reduced floating and increased active behaviors in the FST. Chronic administration of 6 microg/kg prepro-TRH 178-199 decreased floating more than subacute treatment, but there were no significant differences between chronic and subacute treatment effects on active behavior. Biological activity of this peptide resides in the C-terminal fragment as prepro-TRH 178-199 and prepro-TRH 191-199 were equally potent in the FST. These data suggest that endogenous prepro-TRH 178-199 with its antidepressant-like activity might contribute to the etiology or manifestation of depressive behavior.

  20. Effect of thioperamide on modified forced swimming test-induced oxidative stress in mice.

    PubMed

    Akhtar, Mohd; Pillai, K K; Vohora, Divya

    2005-10-01

    This study was designed i) to investigate the role of histamine H3-receptor ligands on mouse modified forced swimming test, a method that distinguishes the catecholaminergic behaviour with that of serotonergic compounds and ii) to evaluate the role of free radicals in mediation of such effects. Swiss strain albino mice were treated with different doses of histamine H3-receptor antagonist thioperamide (3.75, 7.5 and 15 mg/kg intraperitoneally) and agonist (R)-alpha-methylhistamine (5 microg intracerebroventricularly). The climbing, swimming and immobility times were recorded for 6 min. Immediately after modified forced swimming test, the animals were sacrificed and parameters of oxidative stress were assessed in the brain by measuring the thiobarbituric acid reactive substance (TBARS), glutathione (GSH) and catalase levels. Thioperamide (7.5 and 15 mg/kg intraperitoneally) dose-dependently decreased immobility time and increased swimming time but not climbing time. The behaviour of mice treated with (R)-alpha-methylhistamine was similar to that of control mice. A significant reduction in GSH and an increase in catalase levels were observed in brains of mice exposed to modified forced swimming test. Thioperamide pretreatment dose-dependently reversed such an alteration in oxidative stress parameters. (R)-alpha-methylhistamine caused a reversal of altered catalase but not GSH levels. Thioperamide shows antidepressant effects in the modified forced swimming test and causes a reversal of the test-induced oxidative stress indicating its antioxidant potential. The antidepressant effect of thioperamide appears to be mediated via serotonergic and/or antioxidant mechanisms.

  1. Differential effect of low doses of intracerebroventricular corticotropin-releasing factor in forced swimming test.

    PubMed

    García-Lecumberri, C; Ambrosio, E

    2000-11-01

    In this work, we studied the effect of low doses of intracerebroventricular corticotropin-releasing factor (CRF) in six sessions of forced swimming test (FST). When CRF (0.01 and 0.1 microg) was administered pre-test, results showed that the 0.1-microg dose significantly increased swimming in SESSION2, SESSION3 and SESSION4, while the 0.01-microg dose proved ineffective. When CRF (0.1 and 0.03 microg) was administered post-test to evaluate retention of swimming response, the dose of 0.1 microg impaired retention, while the dose of 0.03 microg improved it, although these effects only reached significance in SESSION2. In an additional session (SESSION6), testing long-term retention of this swimming response, the 0.1-microg dose significantly impaired retention, whereas the 0.03-microg dose proved ineffective. A high dose of CRF (1 microg) was also included as a control of previous results [García-Lecumberri C, Ambrosio E. Role of corticotropin-releasing factor in forced swimming test. Eur J Pharmacol 1998;343:17-26]. In all the FST sessions, this high dose increased swimming when administered pre-test, while impairing retention when administered post-test. Preliminary data obtained with low doses of CRF suggest that a differential effect on retention of swimming response seems to exist depending on the dose, whereas a high dose of CRF clearly impairs retention. The role of CRF in learning and memory processes in FST is discussed.

  2. Variability in Measurement of Swimming Forces: A Meta-Analysis of Passive and Active Drag

    ERIC Educational Resources Information Center

    Havriluk, Rod

    2007-01-01

    An analysis was conducted to identify sources of true and error variance in measuring swimming drag force to draw valid conclusions about performance factor effects. Passive drag studies were grouped according to methodological differences: tow line in pool, tow line in flume, and carriage in tow tank. Active drag studies were grouped according to…

  3. Performance Level Differences in Swimming: A Meta-Analysis of Passive Drag Force

    ERIC Educational Resources Information Center

    Havriluk, Rod

    2005-01-01

    The streamline is a basic position for competitive swimming starts mid turns and has been used in many studies on resistive forces. However, there is a wide yahweh, of theoretical interpretations in these studies, leading to diverse and questionable conclusions. The purpose of this study was to determine performance level differences in the…

  4. Effects of zinc supplementation on the element distribution in kidney tissue of diabetic rats subjected to acute swimming.

    PubMed

    Sivrikaya, Abdullah; Bicer, Mursel; Akil, Mustafa; Baltaci, Abdulkerim Kasim; Mogulkoc, Rasim

    2012-06-01

    In this study, we report the effect of zinc supplementation on the distribution of elements in kidney tissue of diabetic rats subjected to acute swimming exercise. Diabetes was induced by two subcutaneous injections of 40 mg/kg of streptozotocin within a 24-h period. Zinc was given intraperitoneally at a dose of 6 mg/kg per day for a period of 4 weeks. The rats (n = 80) were equally divided into eight study groups: controls, zinc-supplemented, swimming, diabetic, zinc-supplemented diabetic, zinc-supplemented swimming, diabetic swimming, and zinc-supplemented diabetic swimming. The levels of lead, cobalt, molybdenum, chromium, boron, magnesium, iron, copper, calcium, zinc, and selenium were determined in the kidney tissue samples by ICP-AES. Higher molybdenum, calcium, zinc, and selenium values were found in both swimming and nonswimming diabetic rats. Significantly higher iron values were found in swimming, diabetic, diabetic swimming, and zinc-supplemented diabetic swimming rats (p < 0.001). Diabetic, zinc-supplemented diabetic, diabetic swimming, and zinc-supplemented diabetic swimming rats had the highest copper values. These results show that zinc supplementation normalized the higher levels of molybdenum, calcium, selenium, and iron levels seen in diabetic rats, indicating that zinc may have a regulatory effect on element metabolism in kidney tissue. PMID:22161314

  5. Ventral tegmental area cholinergic mechanisms mediate behavioral responses in the forced swim test.

    PubMed

    Addy, N A; Nunes, E J; Wickham, R J

    2015-07-15

    Recent studies revealed a causal link between ventral tegmental area (VTA) phasic dopamine (DA) activity and pro-depressive and antidepressant-like behavioral responses in rodent models of depression. Cholinergic activity in the VTA has been demonstrated to regulate phasic DA activity, but the role of VTA cholinergic mechanisms in depression-related behavior is unclear. The goal of this study was to determine whether pharmacological manipulation of VTA cholinergic activity altered behavioral responding in the forced swim test (FST) in rats. Here, male Sprague-Dawley rats received systemic or VTA-specific administration of the acetylcholinesterase inhibitor, physostigmine (systemic; 0.06 or 0.125mg/kg, intra-cranial; 1 or 2μg/side), the muscarinic acetylcholine receptor (AChR) antagonist scopolamine (2.4 or 24μg/side), or the nicotinic AChR antagonist mecamylamine (3 or 30μg/side), prior to the FST test session. In control experiments, locomotor activity was also examined following systemic and intra-cranial administration of cholinergic drugs. Physostigmine administration, either systemically or directly into the VTA, significantly increased immobility time in FST, whereas physostigmine infusion into a dorsal control site did not alter immobility time. In contrast, VTA infusion of either scopolamine or mecamylamine decreased immobility time, consistent with an antidepressant-like effect. Finally, the VTA physostigmine-induced increase in immobility was blocked by co-administration with scopolamine, but unaltered by co-administration with mecamylamine. These data show that enhancing VTA cholinergic tone and blocking VTA AChRs has opposing effects in FST. Together, the findings provide evidence for a role of VTA cholinergic mechanisms in behavioral responses in FST.

  6. Allopregnanolone microinjected into the lateral septum or dorsal hippocampus reduces immobility in the forced swim test: participation of the GABAA receptor.

    PubMed

    Rodríguez-Landa, Juan Francisco; Contreras, Carlos M; García-Ríos, Rosa Isela

    2009-10-01

    Allopregnanolone is a 5α-reduced metabolite of progesterone with actions on γ-aminobutyric acid-A (GABAA) receptors that produce antidepressant-like effects. However, little is known about the target brain regions that mediate its antidepressant-like effects. In this study, allopregnanolone (2.0 μg/0.3 μl/rat) or its vehicle (35% cyclodextrin solution) were microinjected into the lateral septum, septofimbrial, or dorsal hippocampus of male Wistar rats that had previously received intraperitoneal injections of either saline or the GABAA antagonist bicuculline (1.0 mg/kg), and its effects were evaluated in the open field and forced swim tests. Allopregnanolone microinjected into the lateral septum or dorsal hippocampus, but not septofimbrial nucleus, induced a longer latency to the first immobility and a shorter total immobility time in the forced swim test compared with vehicle. Bicuculline pretreatment reversed the effect of allopregnanolone. None of the treatments produced significant changes in crossings in the open field test. In conclusion, allopregnanolone produces an antidepressant-like effect in rats submitted to the forced swim test through actions on GABAA receptors located in the lateral septum and dorsal hippocampus, which is consistent with the antistress effect of GABAA agonists in these particular brain structures.

  7. Prolonged swimming exercise does not affect contents and fatty acids composition of rat muscle triacylglycerol.

    PubMed

    Ochiai, Masaru; Matsuo, Tatsuhiro

    2009-01-01

    The present study investigated whether or not muscle triacylglycerol (MTG) contributed as a main energy source and MTG level and utilized fatty acid (FA) composition decreased during a 4-hour swimming exercise in rats fed a normal diet or a high-fat diet (HFD). Sixty male Wistar rats aged 5 weeks were fed a normal diet (CE-2, n = 25, experiment A) or HFD (n = 35, experiment B) for 22 days. On the final day, rats in both experiments were killed either without exercise or 1, 2, 3, or 4 hours after beginning the swimming exercise. MTG accumulation was higher in rats fed the HFD than those fed the CE-2 in both slow- and fast-typed muscles. Serum concentrations of free fatty acids (FFA) and glucose were increased and muscle glycogen contents were decreased with the continuance of swimming exercise, especially in rats fed the CE-2. The prolonged swimming did not influence MTG contents and FA compositions of MTG in either the experiment. These results might indicate that specific FA of MTG was not oxidized and MTG did not contribute as a main energy source during the prolonged swimming exercise in rats; instead, serum FFA, glucose, and muscle glycogen were mainly used.

  8. Backstroke swimming: exploring gender differences in passive drag and instantaneous net drag force.

    PubMed

    Formosa, Danielle P; Sayers, Mark Gregory Leigh; Burkett, Brendan

    2013-12-01

    This study explored and quantified gender differences in passive drag and instantaneous net drag force profile for elite backstroke swimmers (FINA points 938 ± 71). Nine female and ten male backstroke swimmers completed eight maximum speed trials. During the passive drag condition participants were towed at the speed achieved within the maximum effort backstroke swimming trials, while holding a supine stationary streamline position. The remaining trials, swimmers performed their natural swimming stroke, while attached to an assisted towing device. Male participant's passive (P < .001) and mean net drag force (P < .001) were significantly higher compared with female participants. In addition, there were no significant differences by gender between either the minimum or maximum net drag forces produced during the left and right arm strokes. Instantaneous net drag force profiles demonstrated differences within and between individuals and genders. The swimmers who recorded the fastest speed also recorded the smallest difference in net drag force fluctuations. The instantaneous net drag force profile within elite backstroke swimming provides further insight into stroke technique of this sport.

  9. Backstroke swimming: exploring gender differences in passive drag and instantaneous net drag force.

    PubMed

    Formosa, Danielle P; Sayers, Mark Gregory Leigh; Burkett, Brendan

    2013-12-01

    This study explored and quantified gender differences in passive drag and instantaneous net drag force profile for elite backstroke swimmers (FINA points 938 ± 71). Nine female and ten male backstroke swimmers completed eight maximum speed trials. During the passive drag condition participants were towed at the speed achieved within the maximum effort backstroke swimming trials, while holding a supine stationary streamline position. The remaining trials, swimmers performed their natural swimming stroke, while attached to an assisted towing device. Male participant's passive (P < .001) and mean net drag force (P < .001) were significantly higher compared with female participants. In addition, there were no significant differences by gender between either the minimum or maximum net drag forces produced during the left and right arm strokes. Instantaneous net drag force profiles demonstrated differences within and between individuals and genders. The swimmers who recorded the fastest speed also recorded the smallest difference in net drag force fluctuations. The instantaneous net drag force profile within elite backstroke swimming provides further insight into stroke technique of this sport. PMID:23271003

  10. Behavioral and pharmacological validation of the gerbil forced-swim test: effects of neurokinin-1 receptor antagonists.

    PubMed

    Wallace-Boone, Tanya L; Newton, Amy E; Wright, Robert N; Lodge, Nicholas J; McElroy, John F

    2008-07-01

    Several studies have suggested that neurokinin-1 (NK1) receptor antagonists may have therapeutic potential as novel antidepressant drugs. To test these compounds preclinically, gerbils have become one of the preferred species in that they demonstrate close NK1 receptor homology with humans and bind NK1 antagonists with higher affinity than rats and mice. The intent of the present study was to determine whether the forced-swim test (FST), one of the most commonly used animal tests of antidepressant-like activity, could be adapted for use with the gerbil. Critical factors in the establishment of this assay included swim tank diameter, weight, and sex of the animals tested. Pharmacological validation of the FST using standard antidepressant compounds (eg fluoxetine, paroxetine, desipramine) resulted in decreased immobility time during the test, indicative of an antidepressant-like effect. Similar to results reported for the rat and mouse FST, the antipsychotic drug haloperidol increased immobility, whereas the psychostimulant, amphetamine decreased immobility, and anxiolytic drugs (eg buspirone) had no effect. Investigation into the locomotor effects of all compounds tested was consistent with previous reports in other species, with the exception of paroxetine, which produced hyperactivity at therapeutically effective doses in gerbils. In addition to standard antidepressants, NK1 antagonists (L-733060, MK-869, and CP-122721) all reduced immobility in the gerbil FST without affecting locomotor activity. Overall, these results suggest that the gerbil is an ideal species for use in the FST, and that this paradigm may have predictive validity for identifying novel antidepressant compounds.

  11. The Effect of Warm-up on Tethered Front Crawl Swimming Forces

    PubMed Central

    Neiva, Henrique; Morouço, Pedro; Silva, António J.; Marques, Mário C.; Marinho, Daniel A.

    2011-01-01

    This study was conducted to determine the effect of warm-up on high-intensity front crawl tethered swimming and thus to better understand possible variations in the force exerted by the swimmers. Ten male national level swimmers (mean ± SD; age 15.3 ± 0.95 years old, height: 1.73 ± 5.2 m, body mass: 64.3 ± 7.8 kg, Fat mass 8.31 ± 3.1 kg) participated in this study. After a typical competition warm-up, the subjects performed a 30 s tethered swimming all-out effort in front crawl swimming technique. The same test was repeated in the day after but performed without warming up. Capillary blood lactate concentration was assessed before and after the swimming test and the Borg ratings of perceived exertion scale was used. Without a previous warm-up, the mean ± SD values of maximum and mean forces were 299.62 ± 77.56 N and 91.65 ± 14.70 N, respectively. These values were different (p<0.05) from the values obtained with warm-up (351.33 ± 81.85 N and 103.97 ± 19.11 N). Differences were also observed when regarding to the forces relative to body mass. However, the values of lactate net concentrations after the test performed with and without warm-up were not different (6.27 ± 2.36 mmol·l−1 and 6.18 ± 2.353 mmol·l −1) and the same occurs with the values of ratings of perceived exertion (15.90 ± 2.42 and 15.60 ± 2.27). These results suggest an improvement of the maximum and mean force of the swimmer on the tethered swimming due to previous warm-up. PMID:23486375

  12. Long lasting increase in nociceptive threshold induced in mice by forced swimming: involvement of an endorphinergic mechanism.

    PubMed

    Suaudeau, C; Costentin, J

    2000-05-01

    Mice submitted to forced swimming session(s) displayed a long lasting modification in their nociceptive threshold, assessed through their jump latency from a hot plate (55 degrees C). Thus two forced swimming sessions (6 min each, 8h apart), in water at 33 degrees C, increased by about 50% the jump latency when the hot plate test was performed 14 hours, 3 days or 6 days thereafter. The water temperature (16 degrees C vs 33 degrees C) had no critical influence in this respect. To be clearly effective (at 33 degrees C) the swimming session had to be performed twice (when performed only once it was irregularly effective); it apparently culminated for a 6 min duration, since its effectiveness was not significantly increased by extending the swimming time to 12 min or 18 min. Performing 2 forced swimming sessions (6 min each, 8h apart), 5 consecutive days, resulted in a suppression of the increase in jump latency in the hot plate test. The two forced swimming episodes-induced analgesia was prevented by the s.c. administration of diazepam (from 0.125 mg/kg) or morphine (from 5 mg/kg) or scopolamine (1 mg/kg) before each forced swimming episode. Morphine (7.5 mg/kg) was uneffective to prevent the induction of two forced swimming episodes-induced analgesia when it was administered immediately after each forced swimming session. Finally this analgesia was dose dependently reversed by naloxone (ID(50) = 0.14 mg/kg, s.c., 30 min before the hot plate test). It is hypothesized that the handling of mice immediately before the hot plate test induces the remembrance of the stress induced by previous forced swimming episodes, triggering a fear reaction which increases the nociceptive threshold. PMID:10938583

  13. Forced sustained swimming exercise at optimal speed enhances growth of juvenile yellowtail kingfish (Seriola lalandi).

    PubMed

    Palstra, Arjan P; Mes, Daan; Kusters, Kasper; Roques, Jonathan A C; Flik, Gert; Kloet, Kees; Blonk, Robbert J W

    2014-01-01

    Swimming exercise at optimal speed may optimize growth performance of yellowtail kingfish in a recirculating aquaculture system. Therefore, optimal swimming speeds (U opt in m s(-1) or body lengths s(-1), BL s(-1)) were assessed and then applied to determine the effects of long-term forced and sustained swimming at U opt on growth performance of juvenile yellowtail kingfish. U opt was quantified in Blazka-type swim-tunnels for 145, 206, and 311 mm juveniles resulting in values of: (1) 0.70 m s(-1) or 4.83 BL s(-1), (2) 0.82 m s(-1) or 3.25 BL s(-1), and (3) 0.85 m s(-1) or 2.73 BL s(-1). Combined with literature data from larger fish, a relation of U opt (BL s(-1)) = 234.07(BL)(-0.779) (R (2) = 0.9909) was established for this species. Yellowtail kingfish, either forced to perform sustained swimming exercise at an optimal speed of 2.46 BL s(-1) ("swimmers") or allowed to perform spontaneous activity at low water flow ("resters") in a newly designed 3600 L oval flume (with flow created by an impeller driven by an electric motor), were then compared. At the start of the experiment, ten fish were sampled representing the initial condition. After 18 days, swimmers (n = 23) showed a 92% greater increase in BL and 46% greater increase in BW as compared to resters (n = 23). As both groups were fed equal rations, feed conversion ratio (FCR) for swimmers was 1.21 vs. 1.74 for resters. Doppler ultrasound imaging showed a statistically significant higher blood flow (31%) in the ventral aorta of swimmers vs. resters (44 ± 3 vs. 34 ± 3 mL min(-1), respectively, under anesthesia). Thus, growth performance can be rapidly improved by optimal swimming, without larger feed investments. PMID:25620933

  14. Forced sustained swimming exercise at optimal speed enhances growth of juvenile yellowtail kingfish (Seriola lalandi)

    PubMed Central

    Palstra, Arjan P.; Mes, Daan; Kusters, Kasper; Roques, Jonathan A. C.; Flik, Gert; Kloet, Kees; Blonk, Robbert J. W.

    2015-01-01

    Swimming exercise at optimal speed may optimize growth performance of yellowtail kingfish in a recirculating aquaculture system. Therefore, optimal swimming speeds (Uopt in m s−1 or body lengths s−1, BL s−1) were assessed and then applied to determine the effects of long-term forced and sustained swimming at Uopt on growth performance of juvenile yellowtail kingfish. Uopt was quantified in Blazka-type swim-tunnels for 145, 206, and 311 mm juveniles resulting in values of: (1) 0.70 m s−1 or 4.83 BL s−1, (2) 0.82 m s−1 or 3.25 BL s−1, and (3) 0.85 m s−1 or 2.73 BL s−1. Combined with literature data from larger fish, a relation of Uopt (BL s−1) = 234.07(BL)−0.779 (R2 = 0.9909) was established for this species. Yellowtail kingfish, either forced to perform sustained swimming exercise at an optimal speed of 2.46 BL s−1 (“swimmers”) or allowed to perform spontaneous activity at low water flow (“resters”) in a newly designed 3600 L oval flume (with flow created by an impeller driven by an electric motor), were then compared. At the start of the experiment, ten fish were sampled representing the initial condition. After 18 days, swimmers (n = 23) showed a 92% greater increase in BL and 46% greater increase in BW as compared to resters (n = 23). As both groups were fed equal rations, feed conversion ratio (FCR) for swimmers was 1.21 vs. 1.74 for resters. Doppler ultrasound imaging showed a statistically significant higher blood flow (31%) in the ventral aorta of swimmers vs. resters (44 ± 3 vs. 34 ± 3 mL min−1, respectively, under anesthesia). Thus, growth performance can be rapidly improved by optimal swimming, without larger feed investments. PMID:25620933

  15. Skin-friction drag analysis from the forced convection modeling in simplified underwater swimming.

    PubMed

    Polidori, G; Taïar, R; Fohanno, S; Mai, T H; Lodini, A

    2006-01-01

    This study deals with skin-friction drag analysis in underwater swimming. Although lower than profile drag, skin-friction drag remains significant and is the second and only other contribution to total drag in the case of underwater swimming. The question arises whether varying the thermal gradient between the underwater swimmer and the pool water may modify the surface shear stress distribution and the resulting skin-friction drag acting on a swimmer's body. As far as the authors are aware, such a question has not previously been addressed. Therefore, the purpose of this study was to quantify the effect of this thermal gradient by using the integral formalism applied to the forced convection theory. From a simplified model in a range of pool temperatures (20-30 degrees C) it was demonstrated that, whatever the swimming speeds, a 5.3% reduction in the skin-friction drag would occur with increasing average boundary-layer temperature provided that the flow remained laminar. However, as the majority of the flow is actually turbulent, a turbulent flow analysis leads to the major conclusion that friction drag is a function of underwater speed, leading to a possible 1.5% reduction for fast swimming speeds above 1m/s. Furthermore, simple correlations between the surface shear stress and resulting skin-friction drag are derived in terms of the boundary-layer temperature, which may be readily used in underwater swimming situations.

  16. Swimming and running through sand: resistive force theory in granular media

    NASA Astrophysics Data System (ADS)

    Goldman, Daniel

    2013-11-01

    Resistive force theory (RFT) is often used to analyze the movement of microscopic organisms swimming in fluids. In RFT, a body is partitioned into infinitesimal segments, each of which generates thrust and experiences drag. Linear superposition of forces from elements over the body allows prediction of swimming kinematics and kinetics. While RFT does not always show quantitative agreement with experimental measurements in fluids [e.g. Rodenborn et al., PNAS, 2013], we show that it quantitatively models the locomotion of animals and robots that move on and within dry granular media. RFT shows excellent agreement when the medium is slightly polydisperse, in the regime where frictional forces dominate material inertial forces, and when locomotion can be approximated as confined to a plane. Within a given plane (horizontal or vertical) relationships that govern the force versus orientation of an elemental intruder are functionally independent of the granular medium. We use RFT to explain features of locomotion-these include muscle activation patterns during sand-swimming by the sandfish lizard and optimum limb shape for legged robot walking. Work supported by NSF and ARL.

  17. Effects of crude oil and swimming behavior and survival in the rice rat

    USGS Publications Warehouse

    Wolfe, J.L.; Esher, R.J.

    1981-01-01

    Oil slicks in laboratory test chambers inhibited swimming behavior of rice rats, and reduced survival at low temperature. Predisposition to enter the water and swim was greatly reduced at both high (200 ml/m2 water surface) and low (20 ml/m2) concentrations of oil. Survival was significantly affected only at high concentrations. The results may be of value in predicting the impact of oil spills on the mammal community of coastal marshes.

  18. Effects of neonatal exposure to paint thinner on the development of swimming in rats.

    PubMed

    Lorenzana-Jiménez, M; Salas, M

    1980-01-01

    Rats were exposed to paint thinner twice a day for a period of 10 minutes on Days 1 through 30 of postnatal life. The subsequent effects upon physical development, swimming ability and escape latency from water were evaluated. Maturation of swimming behavior and general physical development were delayed about 2-4 days in the experimental animals compared with non-exposed littermate controls. The results of these experiments suggest that exposure to this organic solvent during the early postnatal period interferes with the development of the cortico-subcortical neural structures underlying swimming and locomotion. PMID:7442917

  19. Determination of Force Coresponding to Maximal Lactate Steady State in Tethered Swimming

    PubMed Central

    PAPOTI, MARCELO; VITÓRIO, RICARDO; ARAÚJO, GUSTAVO G.; DA SILVA, ADELINO S. R.; SANTHIAGO, VANESSA; MARTINS, LUIZ E. B.; CUNHA, SÉRGIO A.; GOBATTO, CLAUDIO A.

    2009-01-01

    The main aim of the present investigation was to verify if the aerobic capacity (AC) measured in tethered swimming corresponds to the maximal lactate steady state (MLSS) and its correlation with 30 min and 400m free style swimming. Twenty-five swimmers were submitted to an incremental tethered swimming test (ITS) with an initial load of 20N and increments of 10N each 3min. After each stage of 3min, the athletes had 30s of interval to blood sample collections that were used to measure blood lactate concentrations ([La−]). The ACBI was determined by the abrupt increase in [La−] versus force (F). The points obtained between [La−] versus force (N) were adjusted by an exponential curve model to determine AC corresponding to 3.5mmol.l−1 (AC3.5) and 4.0mmol.l−1 (AC4.0). After these procedures, the swimmers performed maximal efforts of 30min and 400m in free style swimming. We used the distance performed in 30min and the time performed in 400m to calculate the median velocities (i.e. V30 and V400) of these protocols. After one week, in order to measure the MLSS, nine athletes performed three 30-min tethered swimming efforts with intensities of 90, 100, and 110% of ACBI. The ANOVA one-way was used to compare the ACBI, AC3.5 and AC4.0. Correlations between ACs, and between ACs and V30 and V400 (p<0.05) were determined using the Pearson’s correlation coefficient. The intensity corresponding to 100% of ACBI was similar to the MLSS. It was observed significant correlations of the aerobic capacities (i.e. ACBI, AC3.5 and AC4.0) with V30 (r>0.91) and V400 (r>0.63). According to our results, it is possible to conclude that the ACBI corresponds to the MLSS, and both the AC - individually determined - and the AC - determined using fixed blood lactate concentrations of 3.5 and 4.0mmol.l−1 - can be used to predict the mean velocity of 30min and 400m in free style swimming. In addition to that, the tethered swimming system can be used for aerobic development in places

  20. Administration of orexin receptor 1 antagonist into the rostral ventromedial medulla increased swim stress-induced antinociception in rat

    PubMed Central

    Soliemani, Neda; Moslem, Alireza; Shamsizadeh, Ali; Azhdari-Zarmehri, Hassan

    2016-01-01

    Objective(s): Intracerebroventricular injection of orexin-A (hypocretin-1) antagonist has been shown to inhibit stress-induced analgesia. However the locations of central sites that may mediate these effects have not been totally demonstrated. This study was performed to investigate the role of rostral ventromedial medulla (RVM) orexin receptor 1 in stress-induced analgesia (SIA). Materials and Methods: Forced swim stress in water was employed to adult male rats (200-250 g). Nociceptive responses were measured by formalin test (50 µl injection of formalin 2% subcutaneously into hind paw) and, pain related behaviors were monitored for 90 min following intra-microinjection of SB-334867 (orexin receptor 1 antagonist) into RVM. Results: Exposure to swimming stress test after administration of SB-334867 into RVM significantly reduces the formalin-induced nociceptive behaviors in phase1, interphase, and phase 2 in rats. Conclusion: The result demonstrated the involvement of OXR1 in antinociceptive behaviors induced by swim stress in RVM. PMID:27403261

  1. 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.

  2. Clonidine as a sensitizing agent in the forced swimming test for revealing antidepressant activity.

    PubMed

    Bourin, M; Colombel, M C; Malinge, M; Bradwejn, J

    1991-11-01

    The forced swimming test (FST) in mice has failed to predict antidepressant activity for drugs having beta adrenoreceptor agonist activity and for serotonin uptake inhibitors. We investigated the potential for clonidine to render the FST sensitive to antidepressants by using a behaviorally inactive dose of this agent (0.1 mg/kg). All antidepressants studied (tricyclics, 5-HT uptake inhibitors, iprindole, mianserin, viloxazine, trazodone) showed either activity at lower doses or activity at previously inactive doses. The effect appeared specific because it did not appear with drugs other than antidepressants (diazepam, chlorpromazine, sulpiride, atropine), except for amphetamine and apomorphine which have a strong effect on the dopaminergic system. The use of behaviorally subactive doses of clonidine may thus provide an important means of increasing the sensitivity of the forced swimming test.

  3. Using Magnetic Forces to Probe the Gravi-response of Swimming Paramecium

    NASA Astrophysics Data System (ADS)

    Guevorkian, Karine; Valles, James M., Jr.

    2004-03-01

    Paramecium Caudatum, a single celled ciliate, alters its swimming behavior when subjected to different gravity environments (e.g. centrifugation and micro-gravity). To dissect the mechanisms behind this gravi-response and that of other biological systems, we are developing the use of magnetic body forces as a means of creating a rapidly tunable, simulated variable gravity environment. Since biological materials are weakly diamagnetic, we must subject them to intense inhomogeneous magnetic fields with characteristic field-field gradient products on the order of 16 T^2/cm. We will describe experiments on Paramecium Caudatum in which we adjust their net buoyancy with magnetic forces and measure the resulting changes in their swimming behavior.

  4. [Unpredictable chronic mild stress effects on antidepressants activities in forced swim test].

    PubMed

    Kudryashov, N V; Kalinina, T S; Voronina, T A

    2015-02-01

    The experiments has been designed to study unpredictable chronic mild stress effect on anti-depressive activities of amitriptyline (10 mg/kg) and fluoxetine (20 mg/kg) in forced swim test in male outbred mice. It is shown that acute treatment with fluoxetine does not produce any antidepressant effects in mice following stress of 14 days while the sub-chronic injections of fluoxetine result in more deep depressive-like behavior. In 28 daily stressed mice, antidepressant effect of fluoxetine is observed independently of the injection rates. Amitriptyline demonstrates the antidepressant activity regardless of the duration of stress or administration scheduling, but at the same time the severity of anti-immobilization effect of amitriptyline in stressed mice is weaker in compare to non-stressed trails. Thus, the injection rates and duration of unpredictable mild chronic stress are the parameters that determine the efficiency of antidepressants in the mouse forced swimming test.

  5. The influence of the breathing action on net drag force production in front crawl swimming.

    PubMed

    Formosa, D; Sayers, M G L; Burkett, B

    2014-12-01

    20 elite swimmers completed a total of 6 randomized net drag force trials in 2 conditions (i) 3 breathing and (ii) 3 non-breathing. Net drag force was measured using an assisted motorized dynamometer device mounted upon a Kistler force-platform. The male participants demonstrated no statistical differences in stroke rates between breathing and non-breathing trials. Female participants, however, demonstrated a statistical difference stroke rate. The male participants demonstrated that the breathing action caused a greater (26%) net drag force compared to the females (16%). To further understand the influence of breathing on swimming technique, each stroke was analyzed and comparisons were made between the breathing and non-breathing conditions. The male participants demonstrated a similar minimum net drag force when comparing the breathing and non-breathing conditions. Analysis showed that minimum net drag force and maximum net drag force for the males changed when integrating the breathing action, while female participants demonstrated similar swimming technique, regardless of condition or stroke.

  6. Post-activation Potentiation in Propulsive Force after Specific Swimming Strength Training.

    PubMed

    Barbosa, A C; Barroso, R; Andries, O

    2016-04-01

    We investigated whether a conditioning activity (8×12.5 m with 2.5 min-interval using both hand paddles and parachute) induced post-activation potentiation in swimming propulsive force and whether a swimmer's force level affected a post-activation potentiation response. 8 competitive swimmers (5 males and 3 females, age: 18.4±1.3 years; IPS=796±56) performed a 10 s maximum tethered swimming test 8 and 4 min before (the highest value was considered as PRE), and 2.5 and 6.5 min after (POST1 and POST2, respectively) the conditioning activity. Rate of force development was not affected, but peak force in POST1 (p=0.02) and impulse in both POST1 (p=0.007) and POST2 (p=0.004) were reduced. Possibly the conditioning activity induced greater fatigue than post-activation potentiation benefits. For instance, the number of repetitions might have been excessive, and rest intervals between the conditioning activity and POST1 and POST2 were possibly too short. There were positive correlations between PRE peak force and changes in peak force and rate of force development. Although conditioning activity was detrimental, positive correlations suggest that weaker swimmers experience a deterioration of performance more than the stronger ones. This conditioning activity is not recommended for swimmers with the current competitive level before a competitive event. PMID:26667922

  7. Endocrine and immunological correlates of behaviorally identified swim stress resilient and vulnerable rats.

    PubMed

    Levay, Elizabeth A; Govic, Antonina; Hazi, Agnes; Flannery, Graham; Christianson, John; Drugan, Robert C; Kent, Stephen

    2006-09-01

    Animal models of stress-induced depression have identified a bimodal reactivity to stress, namely 'resilience' and 'vulnerability.' Possible corresponding differences in endocrine and immunological responses between these groups have not been delineated. Male Sprague-Dawley rats were divided into three groups: stress (n=25), confined controls (n=7), and home cage controls (n=7). Stress rats were exposed to 80, 5-s inescapable cold water swim trials (15 degrees C). Twenty-four hours later, the stress rats were tested on an instrumental swim escape test (SET) but now they had access to an omnidirectional lever that terminated the stress. Immediately after the SET, trunk blood was collected to assay for serum corticosterone (CORT), and spleens were removed and natural killer cell activity (NKCA) and concanavalin A (CON-A) induced lymphocyte proliferation determined. Subjects in the stress treatment group were divided into distinct 'resilient' and 'vulnerable' categories by a median split for average escape latencies across the last 25 trials of the SET. Stress rats secreted more CORT than controls and vulnerable rats secreted greater levels than resilient rats. NKCA was greatest in control rats, and was decreased in the stress rats although the resilient and the vulnerable groups did not differ. Conversely, CON-A-induced lymphocyte proliferation was greatest in stress rats, vulnerable rats exhibiting more proliferation than resilient rats, but both were greater than both control groups. Stress animals were hypothermic throughout the swim stress procedures but exhibited a stress-induced fever following the initial swim trials. The observed differences may have important predictive and theoretical utility for vulnerable and resilient profiles.

  8. Coping with the Forced Swim Stressor: Towards Understanding an Adaptive Mechanism

    PubMed Central

    de Kloet, E. R.; Molendijk, M. L.

    2016-01-01

    In the forced swim test (FST) rodents progressively show increased episodes of immobility if immersed in a beaker with water from where escape is not possible. In this test, a compound qualifies as a potential antidepressant if it prevents or delays the transition to this passive (energy conserving) behavioural style. In the past decade however the switch from active to passive “coping” was used increasingly to describe the phenotype of an animal that has been exposed to a stressful history and/or genetic modification. A PubMed analysis revealed that in a rapidly increasing number of papers (currently more than 2,000) stress-related immobility in the FST is labeled as a depression-like phenotype. In this contribution we will examine the different phases of information processing during coping with the forced swim stressor. For this purpose we focus on the action of corticosterone that is mediated by the closely related mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) in the limbic brain. The evidence available suggests a model in which we propose that the limbic MR-mediated response selection operates in complementary fashion with dopaminergic accumbens/prefrontal executive functions to regulate the transition between active and passive coping styles. Upon rescue from the beaker the preferred, mostly passive, coping style is stored in the memory via a GR-dependent action in the hippocampal dentate gyrus. It is concluded that the rodent's behavioural response to a forced swim stressor does not reflect depression. Rather the forced swim experience provides a unique paradigm to investigate the mechanistic underpinning of stress coping and adaptation. PMID:27034848

  9. Novel insights into the behavioral analysis of mice subjected to the forced-swim test.

    PubMed

    Chen, L; Faas, G C; Ferando, I; Mody, I

    2015-04-14

    The forced-swim test (FST) is one of the most widely used rodent behavioral assays, in which the immobility of animals is used to assess the effectiveness of antidepressant drugs. However, the existing, and mostly arbitrary, criteria used for quantification could lead to biased results. Here we believe we uncovered new confounding factors, revealed new indices to interpret the behavior of mice and propose an unbiased means for quantification of the FST.

  10. The effects of Creatine Long-Term Supplementation on Muscle Morphology and Swimming Performance in Rats

    PubMed Central

    Yildiz, Ahmet; Ozdemir, Ercan; Gulturk, Sefa; Erdal, Sena

    2009-01-01

    Creatine (Cr) has been shown to increase the total muscle mass. The purpose of this study was to investigate the effect of Cr supplementation on muscle morphology and swimming performance, using an animal model. Each rat was subjected to exercise 15-minute period daily for the 12 weeks. The rats were randomly divided into four groups: no Cr supplementation (CON), no Cr supplementation and incomplete food intake (lacking lysine and methionine in diet for rats) (INCO), Cr supplementation 1 g·kg-1·day-1 (CREAT-I) and Cr supplementation 2 g·kg-1·day-1 (CREAT-II). Three months later, all groups adult rats exercised in swimming pool chambers. Swimming time was recorded as minute for each rat. Following swimming performance period, the animals were killed by cervical dislocation and the gastrocnemius and diaphragm muscles were dissected. Serial slices of 5-7 μm were allocated paraffin wax and histochemical staining procedure of cross-sections was carried out with heamatoxylin-eosin technics. All groups gained body weight at the end of 12 weeks but there was no statistical difference among them. Swimming time values were statistical difference between CREAT-II and CON group as well as between CREAT-I and CON group (p < 0.05). In the INCO group was determined increased connective tissue cell of the muscle sample. In contrast, in the CREAT-I and CREAT-II group, the basic histological changes were large-scale muscle fibers and hypertrophic muscle cells. These results suggest that long-term creatine supplementation increased the number of muscle fibers and enhanced endurance swimming performance in rats. Key points There is no study about the effects of creatine long-term supplementation on muscle morphology and swimming performance in rats. Long-term creatine supplementation increase muscle hypertrophy (but not body weight) and enhance endurance swimming performance in rats. The quantitative analysis indicated that the number of muscle fibers per defined area increased

  11. Measurement of hydrodynamic force generation by swimming dolphins using bubble DPIV.

    PubMed

    Fish, Frank E; Legac, Paul; Williams, Terrie M; Wei, Timothy

    2014-01-15

    Attempts to measure the propulsive forces produced by swimming dolphins have been limited. Previous uses of computational hydrodynamic models and gliding experiments have provided estimates of thrust production by dolphins, but these were indirect tests that relied on various assumptions. The thrust produced by two actively swimming bottlenose dolphins (Tursiops truncatus) was directly measured using digital particle image velocimetry (DPIV). For dolphins swimming in a large outdoor pool, the DPIV method used illuminated microbubbles that were generated in a narrow sheet from a finely porous hose and a compressed air source. The movement of the bubbles was tracked with a high-speed video camera. Dolphins swam at speeds of 0.7 to 3.4 m s(-1) within the bubble sheet oriented along the midsagittal plane of the animal. The wake of the dolphin was visualized as the microbubbles were displaced because of the action of the propulsive flukes and jet flow. The oscillations of the dolphin flukes were shown to generate strong vortices in the wake. Thrust production was measured from the vortex strength through the Kutta-Joukowski theorem of aerodynamics. The dolphins generated up to 700 N during small amplitude swimming and up to 1468 N during large amplitude starts. The results of this study demonstrated that bubble DPIV can be used effectively to measure the thrust produced by large-bodied dolphins.

  12. Effects of Viscosity on the Gravi-kinesis Responses of Swimming Paramecia Studied Using Manetic Force Buoyancy Variation

    NASA Astrophysics Data System (ADS)

    Jung, Ilyong; Valles, James M.

    2013-03-01

    Previous studies have shown that paramecia exhibit negative gravi-kinesis. They exert a stronger propulsive force when swimming up than when swimming down. This behavior is very surprising since it suggests they sense their tiny apparent weight of only ~ 80pN. In an effort to understand the mechanism of this sensing, we are testing how the viscosity of the swimming medium influences their gravi-kinetic response. We employ the technique of magnetic force buoyancy variation to simulate different effective gravity levels on swimming Paramecia. We are analyzing their swimming response employing a phenomenological model that relates the parameters describing their helical trajectories to the beating of their cilia. This work was supported by NSF PHY0750360 and at the NHMFL by NSF DMR-0084173

  13. Scopolamine blocks the effects of swim stress on memory retrieval in rats.

    PubMed

    Kumar, K B; Karanth, K S

    1996-01-01

    This study examined whether application of swim stress improved retrieval of a passive avoidance memory and if pretreatment with the anticholinergic agent, scopolamine, blocked this effect on memory retrieval. Animals initially given a passive avoidance training session were subjected to either a two or four swim stress sessions (15 min each) with or without prior treatment of scopolamine (0.05 or 0.1 mg/kg). The retrieval performance in passive avoidance test and motor activity was assessed 24 hr after the last swim stress session. In an independent control experiment, the passive avoidance training and test were conducted respectively, 24 and 72 hr after the last of four swim stress sessions with or without prior injection of scopolamine (0.1 mg/kg). The results showed an enhanced performance for the passive avoidance task in rats subjected to four swim stress sessions in both experiments and scopolamine given 30 min prior to each stress session diminished this performance of animals in the passive avoidance test. Two swim stress sessions with or without scopolamine treatment caused no significant effects on the retrieval performance. Also, no significant difference was observed among the groups in motor activity following any of the stress treatments in the open field test. These results, thus suggested for the first time, a relationship among swim stress, cholinergic activity and avoidance memory processes.

  14. Swimming exercise alleviates the symptoms of attention-deficit hyperactivity disorder in spontaneous hypertensive rats.

    PubMed

    Ko, Il-Gyu; Kim, Sung-Eun; Kim, Tae-Woon; Ji, Eun-Sang; Shin, Mal-Soon; Kim, Chang-Ju; Hong, Min-Ha; Bahn, Geon Ho

    2013-08-01

    Attention-deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by inattention, hyperactivity and impulsivity. In the present study, we investigated the effects of swimming exercise on the symptoms of ADHD in correlation with the expression levels of dopamine and the dopamine D2 receptor. Adult male spontaneous hypertensive rats (SHRs) were used as animal models of ADHD and Wistar-Kyoto rats were used as controls. The activity, impulsivity and levels of non-aggressive and aggressive behaviors in rats were measured. The short-term memory in the animal models of ADHD was assessed using an open-field test. The social interaction test, elevated plus maze test and step-through avoidance test were additionally performed. The expression levels of tyrosine hydroxylase (TH), which catalyzes the rate‑limiting step of dopamine synthesis, and the dopamine D2 receptor in the prefrontal cortex, substantia nigra and striatum were evaluated. The expression levels of TH and the dopamine D2 receptor were detected using immunohistochemistry and western blotting, respectively. In ADHD rats, the activity, impulsivity and levels of non-aggressive and aggressive behaviors were higher than that in control rats. By contrast, short-term memory in ADHD rats deteriorated. Swimming exercise suppressed hyperactivity, impulsivity and non-aggressive and aggressive behaviors, and alleviated the short-term memory impairment observed in ADHD rats. The expression levels of TH and the dopamine D2 receptor were decreased and increased in ADHD rats, respectively, when compared with control rats. Swimming exercise enhanced the expression of TH and suppressed the expression of the dopamine D2 receptor in ADHD rats. In the present study, swimming exercise improved the symptoms of ADHD by upregulating the expression of dopamine and downregulating the expression of the dopamine D2 receptor. PMID:23779147

  15. Swimming exercise alleviates the symptoms of attention-deficit hyperactivity disorder in spontaneous hypertensive rats.

    PubMed

    Ko, Il-Gyu; Kim, Sung-Eun; Kim, Tae-Woon; Ji, Eun-Sang; Shin, Mal-Soon; Kim, Chang-Ju; Hong, Min-Ha; Bahn, Geon Ho

    2013-08-01

    Attention-deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by inattention, hyperactivity and impulsivity. In the present study, we investigated the effects of swimming exercise on the symptoms of ADHD in correlation with the expression levels of dopamine and the dopamine D2 receptor. Adult male spontaneous hypertensive rats (SHRs) were used as animal models of ADHD and Wistar-Kyoto rats were used as controls. The activity, impulsivity and levels of non-aggressive and aggressive behaviors in rats were measured. The short-term memory in the animal models of ADHD was assessed using an open-field test. The social interaction test, elevated plus maze test and step-through avoidance test were additionally performed. The expression levels of tyrosine hydroxylase (TH), which catalyzes the rate‑limiting step of dopamine synthesis, and the dopamine D2 receptor in the prefrontal cortex, substantia nigra and striatum were evaluated. The expression levels of TH and the dopamine D2 receptor were detected using immunohistochemistry and western blotting, respectively. In ADHD rats, the activity, impulsivity and levels of non-aggressive and aggressive behaviors were higher than that in control rats. By contrast, short-term memory in ADHD rats deteriorated. Swimming exercise suppressed hyperactivity, impulsivity and non-aggressive and aggressive behaviors, and alleviated the short-term memory impairment observed in ADHD rats. The expression levels of TH and the dopamine D2 receptor were decreased and increased in ADHD rats, respectively, when compared with control rats. Swimming exercise enhanced the expression of TH and suppressed the expression of the dopamine D2 receptor in ADHD rats. In the present study, swimming exercise improved the symptoms of ADHD by upregulating the expression of dopamine and downregulating the expression of the dopamine D2 receptor.

  16. Effect of crocin on oxidative stress in recovery from single bout of swimming exercise in rats.

    PubMed

    Altinoz, Eyup; Ozmen, Tarık; Oner, Zulal; Elbe, Hulya; Erdemli, Mehmet E; Bag, Harika G

    2016-01-01

    Physical exercise could cause muscle and tissue damage due to increase in the formation of free oxygen radicals during exercise. The aim of the present study was to investigate the effect of crocin on parameters associated with oxidative stress in recovery from acute swimming exercise in rats. Rats were divided into eight groups; Normal Control (NC: untreated and did not swim), Crocin Control (CC: received crocin and did not swim), Exercise-1 (Exe-1: untreated and swam), Exercise-24 (Exe-24: untreated and swam), Exercise-48 (Exe-48: untreated and swam), Exercise+Crocin-1 (Exe-Cro-1: received crocin and swam), Exercise+Crocin-24 (Exe-Cro-24: received crocin and swam), Exercise+Crocin-48 (Exe-Cro-48: received crocin and swam). AST, ALP, LDH, CK, XO enzymes levels increased after swimming in untreated and crocin-treated groups, but there was a less increase in crocin-treated groups. The highest MDA levels in serum were determined in Exe-1 compared with all other groups. There was significant difference between control and exercise groups in MDA level (p = 0.033). In contrast, there was significant difference between control and exercise groups in GSH level (p < 0.001). In addition, crocin given to swimming rats significantly increased GSH levels (p < 0.05) and decreased MDA levels when compared with untreated exercise groups. In conclusion, crocin is able to protect liver and skeletal muscle tissue against exercise-induced oxidative damage by preventing reactive oxygen species (ROS) production.

  17. Lithium's effect in forced-swim test is blood level dependent but not dependent on weight loss.

    PubMed

    Bersudsky, Yuly; Shaldubina, Alona; Belmaker, R H

    2007-02-01

    The effects of lithium in models of depression are often inconsistent. We aimed to replicate a regimen that induces robust antidepressant effects in the forced-swim test. Mice were treated with three different doses of lithium chloride (LiCl) 0.25, 0.4 or 0.5% in food and the forced-swim test or open field test was performed on day 15. We yoked control mice to food deprivation to test whether lithium-induced food deprivation could cause the lithium effects in the forced-swim test. Treatment with LiCl doses leading to blood levels of 1.3 and 1.4 mmol/l led to highly significant reduction in immobility time in the forced-swim test, but the dose leading to a blood level of 0.8 mmol/l was not different from controls in immobility time. Mice yoked to lithium-induced food deprivation showed no difference in the forced-swim test compared with controls. In conclusion these results suggest that lithium effects in mice in the forced-swim test are dose dependent but not owing to lithium-induced weight loss.

  18. Exposure to forced swim stress alters local circuit activity and plasticity in the dentate gyrus of the hippocampus.

    PubMed

    Yarom, Orli; Maroun, Mouna; Richter-Levin, Gal

    2008-01-01

    Studies have shown that, depending on its severity and context, stress can affect neural plasticity. Most related studies focused on synaptic plasticity and long-term potentiation (LTP) of principle cells. However, evidence suggests that following high-frequency stimulation, which induces LTP in principal cells, modifications also take place at the level of complex interactions with interneurons within the dentate gyrus, that is, at the local circuit level. So far, the possible effects of stress on local circuit activity and plasticity were not studied. Therefore, we set out to examine the possible alterations in local circuit activity and plasticity following exposure to stress. Local circuit activity and plasticity were measured by using frequency dependant inhibition (FDI) and commissural modulation protocols following exposure to a 15 minute-forced swim trial. Exposure to stress did not alter FDI. The application of theta-burst stimulation (TBS) reduced FDI in both control and stressed rats, but this type of plasticity was greater in stressed rats. Commissural-induced inhibition was significantly higher in stressed rats both before and after applying theta-burst stimulation. These findings indicate that the exposure to acute stress affects aspects of local circuit activity and plasticity in the dentate gyrus. It is possible that these alterations underlie some of the behavioral consequences of the stress experience.

  19. Combined intervention of dietary soybean proteins and swim training: effects on bone metabolism in ovariectomized rats.

    PubMed

    Figard, Hélène; Mougin, Fabienne; Gaume, Vincent; Berthelot, Alain

    2006-01-01

    Soybean proteins, a rich source of isoflavones, taken immediately after an ovariectomy prevent bone loss in rats. Exercise-induced stimuli are essential for bone growth. Few studies exist about the combined effects of swim training and soybean protein supplementation on bone metabolism. So, the purpose of this study was to investigate, in 48 female Sprague-Dawley rats (12 weeks old) the effects of an 8-week swim-training regimen (1 h/day, 5 days/week) and dietary soybean proteins (200 g/kg diet) on bone metabolism. Rats were randomly assigned to four groups: (1) ovariectomized fed with a semisynthetic control diet; (2) ovariectomized fed with a soybean protein-enriched semisynthetic diet; (3) ovariectomized trained to exercise and fed with control diet; (4) ovariectomized trained to exercise and fed with a soybean protein diet. Following the treatment period, body weight gain was identical in the four groups. Soybean protein supplementation increased bone calcium content, and reduced plasma osteocalcin values, without significant modification of calcium balance and net calcium absorption. Swim training enhanced plasma and bone calcium content and calcium balance and net calcium absorption. It did not modify either plasma osteocalcin values or urinary deoxypyridinoline excretion. Both exercise and soybean protein intake increased plasma on bone calcium without modifying net calcium absorption or bone markers. In conclusion, we demonstrated, in ovariectomized rats, that swimming exercise and dietary supplementation with soy proteins do not have synergistic effects on calcium metabolism and bone markers.

  20. 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

  1. Involvement of the monoaminergic system in the antidepressant-like activity of chromium chloride in the forced swim test.

    PubMed

    Piotrowska, A; Siwek, A; Wolak, M; Pochwat, B; Szewczyk, B; Opoka, W; Poleszak, E; Nowak, G

    2013-08-01

    Bio-metal chromium(III) is a crucial microelement for the proper functioning of living organisms. Previous preclinical and clinical studies reported its potential antidepressant properties. The aim of the present study was to examine the effect of antidepressants and noradrenergic and dopaminergic receptor antagonists on chromium chloride (CrCl₃) activity in the forced swim test (FST) in mice and rats. Imipramine (5 mg/kg), fluoxetine (5 mg/kg) and reboxetine (5 mg/kg) but not bupropion (1 mg/kg), administered jointly with CrCl₃ at a dose of 6 mg/kg, reduced the immobility time in the FST in mice. The reduction of the immobility time induced by the active dose (12 mg/kg) of CrCl₃ was completely abolished by propranolol (2 mg/kg, β-adrenoceptor antagonist), SCH 23390 (0.5 mg/kg, a dopamine D₁ receptor antagonist), and partially by prazosin (1 mg/kg, an α₁-adrenoceptor antagonist), yohimbine (1 mg/kg, an α₂-adrenoceptor antagonist) and sulpiryd (50 mg/kg, a dopamine D₂/D₃ receptor antagonist) administration. The locomotor activity was significantly reduced by CrCl₃ + reboxetine treatment, which did not influence the reboxetine enhancement of the antidepressant-like effect of CrCl₃ in the FST. Moreover, CrCl₃ at a dose of 32 mg/kg (although not at 12 mg/kg) significantly reduced the immobility and enhanced the climbing (but not swimming) time in the FST in rats, which indicates the involvement of the noradrenergic pathway in this effect. The present study indicates that the antidepressant-like activity of chromium in the FST is dependent (although to a different extent) on the noradrenergic, dopaminergic and serotonin systems.

  2. The additive effects of quinine on antidepressant drugs in the forced swimming test in mice.

    PubMed

    Guo, W Y; Todd, K G; Bourin, M; Hascoet, M

    1995-09-01

    The aim of this study was to investigate if quinine plus antidepressant drugs (ADS) leads to an additive effect in the forced swimming test. Quinine (0.125, 0.5 mg/kg) and ADS (subactive doses) were given IP 45 and 30 min, respectively, before the test. When combined with QUIN, all drugs that act via inhibition of 5-HT uptake (imipramine, amitriptyline, citalopram, paroxetine, fluoxetine and fluvoxamine) significantly increased the swimming time of mice. Among trazodone, mianserin and iprindole (atypical ADS), only iprindole combined with quinine decreased the immobility (increased swimming) of the animals. The specific noradrenaline (NA) uptake inhibitors, desipramine and viloxazine, but not maprotiline, were also found to reduce the immobility time when pretreated with quinine. The mixed monoamine oxidase (MAO) inhibitor (pargyline) and MAO-A inhibitor (moclobemide) also shortened the period of immobility whereas the MAO-B inhibitor (nialamide) and the dopamine (DA) uptake inhibitor (bupropion) did not. Quinine's additive effects on several types of ADS is likely a result of blockade of potassium channels.

  3. Granular resistive force theory explains the neuromechanical phase lag during sand-swimming

    NASA Astrophysics Data System (ADS)

    Ding, Yang; Sharpe, Sarah; Goldman, Daniel

    2012-11-01

    Undulatory locomotion is a common gait used by a diversity of animals in a range of environments. This mode of locomotion is characterized by the propagation of a traveling wave of body bending, which propels the animal in the opposite direction of the wave. Previous studies of undulatory locomotion in fluids, on land, and even within sand revealed that the wave of muscle activation progresses faster than the traveling wave of curvature. This leads to an increasing phase lag between activation and curvature at more posterior segments, known as the neuromechanical phase lag. In this study, we compare biological measurements of phase lag during the sand-swimming of the sandfish lizard to predictions of a simple model of undulatory swimming that consists of prescribed kinematics and granular resistive forces. The neuromechanical phase lag measured using electromyography (EMG) quantitatively matches the predicted phase lag between the local body curvature and torque exerted by granular resistive forces. Two effects are responsible for the phase lag in this system: the yaw motion of the body and different integration length over a traveling force pattern for different positions along the body.

  4. The antidepressant-like effect of ethynyl estradiol is mediated by both serotonergic and noradrenergic systems in the forced swimming test.

    PubMed

    Vega-Rivera, N M; López-Rubalcava, C; Estrada-Camarena, E

    2013-10-10

    17α-Ethynyl-estradiol (EE2, a synthetic steroidal estrogen) induces antidepressant-like effects in the forced swimming test (FST) similar to those induced by 5-HT and noradrenaline reuptake inhibitors (dual antidepressants). However, the precise mechanism of action of EE2 has not been studied. In the present study, the participation of estrogen receptors (ERs) and the serotonergic and the noradrenergic presynaptic sites in the antidepressant-like action of EE2 was evaluated in the FST. The effects of the ER antagonist ICI 182,780 (10 μg/rat; i.c.v.), the serotonergic and noradrenergic terminal destruction with 5,7-dihydroxytryptamine (5,7-DHT; 200 μg/rat, i.c.v.), and N-(2-chloro-ethyl)-N-ethyl-2-bromobenzylamine (DSP4; 10mg/kg, i.p.) were studied in ovariectomized rats treated with EE2 and subjected to the FST. In addition, the participation of α2-adrenergic receptors in the antidepressant-like action of EE2 was explored using the selective α2-receptor antagonist idazoxan (0.25, 0.5 and 1.0mg/kg, i.p.). EE2 induced an antidepressant-like action characterized by a decrease in immobility behavior with a concomitant increase in swimming and climbing behaviors. The ER antagonist, 5,7-DHT, DSP4, and idazoxan blocked the effects of EE2 on the immobility behavior, whereas ICI 182,780 and 5,7-DHT affected swimming behavior. The noradrenergic compound DSP4 altered climbing behavior, while Idazoxan inhibited the increase of swimming and climbing behaviors induced by EE2. Our results suggest that the antidepressant-like action of EE2 implies a complex mechanism of action on monoaminergic systems and estrogen receptors.

  5. Cardiac response to doxorubicin and dexrazoxane in intact and ovariectomized young female rats at rest and after swim training.

    PubMed

    Calvé, Annie; Haddad, Rami; Barama, Sarah-Neiel; Meilleur, Melissa; Sebag, Igal A; Chalifour, Lorraine E

    2012-05-15

    The impact of cancer therapies on adult cardiac function is becoming a concern as more children survive their initial cancer. Cardiovascular disease is now a significant problem to adult survivors of childhood cancer. Specifically, doxorubicin (DOX) may be particularly harmful in young girls. The objective of this study was to characterize DOX damage and determine the ability of dexrazoxane (DEX) to reduce DOX-mediated cardiac damage in sedentary and swim-trained female rats. Female Sprague-Dawley rats were left intact or ovariectomized (OVX) at weaning then injected with DEX (60 mg/kg) before DOX (3 mg/kg), DOX alone, or PBS. Rats were separated into sedentary and swim cohorts. Body weight was reduced in DOX:DEX- but not PBS- or DOX-treated rats. Echocardiographic parameters were similar in sedentary rats. Swim training revealed greater concentric remodeling in DOX-treated rats and reduced fractional shortening in DOX:DEX-treated rats. Calsequestrin 2 was reduced with DOX and increased with DOX:DEX postswim. Sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a was reduced and calsequestrin 2 reduced further by swim training only in intact rats. OVX rats were heavier and developed eccentric remodeling post-swim with DOX and eccentric hypertrophy with DOX:DEX. Changes in SERCA2a and calsequestrin 2 expression were not observed. Ovariectomized DOX- and DOX:DEX-treated rats stopped growing during swim training. DEX coinjection did not relieve DOX-mediated cardiotoxicity in intact or hormone-deficient rats. DOX-mediated reductions in growth, cardiac function, and expression of calcium homeostasis proteins were exacerbated by swim. DEX coadministration did not substantially relieve DOX-mediated cardiotoxicity in young female rats. Ovarian hormones reduce DOX-induced cardiotoxicity.

  6. Depressive-like profile induced by MCH microinjections into the dorsal raphe nucleus evaluated in the forced swim test.

    PubMed

    Lagos, Patricia; Urbanavicius, Jessika; Scorza, María Cecilia; Miraballes, Rodrigo; Torterolo, Pablo

    2011-04-15

    Antagonism of the melanin-concentrating hormone (MCH) receptor 1 (MCH-R1) has been recently shown to have antidepressant-like profile in rats. However, the mechanisms by which the MCHergic system participates in the modulation of emotional states are still to be determined. In the present study we confirmed the presence of MCHergic fibers within the dorsal raphe nucleus (DRN), a serotonergic nucleus involved in the physiopathology of major depression. We also assessed the effects of the administration of MCH and anti-MCH antibody (immunoneutralization) into the DRN using the forced swim test in rats, an animal model to screen antidepressant drugs. We found that a low dose of MCH (50 ng) evoked a depressive-like behavior indicated by a significant increase in the immobility time as well as a decrease in climbing behavior. Furthermore, the depressive-like response was prevented by pretreatment with fluoxetine. Consistent with these results, the immunoneutralization of MCH produced an antidepressant-like effect. By means of the open field test we discarded that these effects were related to unspecific changes in motor activity. Our results suggest that the MCHergic neurons are involved in the regulation of emotional behaviors through the modulation of the serotonergic neuronal activity within the DRN. In addition, the present results are in agreement with previous reports showing that antagonism of the MCHergic system may be a novel therapeutic strategy for the treatment of depressive disorders.

  7. Hesperidin associated with continuous and interval swimming improved biochemical and oxidative biomarkers in rats

    PubMed Central

    2013-01-01

    Background Citrus flavonoids, such as hesperidin, have shown therapeutic properties that improve hyperglycemia and insulin resistance, and decrease blood serum lipids and inflammation. The current investigation studied the effects of hesperidin supplementation associated with continuous and interval swimming on the biochemical parameters (glucose, cholesterol and triglycerides), and oxidative stress markers (TBARS and DPPH) in rats. Methods The animals (n = 60) were randomly divided in six groups: negative (C) and positive control (CH) for hesperidin supplementation, and continuous or interval swimming without (CS and IS) or with hesperidin supplementation (CSH and ISH). Hesperidin was given by gavage for four weeks (100 mg/kg body mass) before the exercise. Continuous swimming was performed for 50 min with loads from 5% to 8 % of body weight from the first to fourth week, while interval swimming training was performed for 50 min in sessions of 1 min of swimming followed by 2 min of resting, carrying loads from 10% to 15, 20 and 25% from the first to fourth week. At the end of the experiment, blood serum samples were draw to perform analysis of glucose, total cholesterol, HDL-C and triglycerides. Oxidative biomarkers were evaluated by lipid peroxidation (TBARS) and antioxidant capacity assay (DPPH) of the blood serum. Results There was a continuous decline of serum glucose from C (100%) > CH (97%) > CS (94%) > CSH (91%, p < .05), IS (87%, p < .05) > ISH (80%, p < .05), showing a combined beneficial effect of hesperidin and swimming. Also, continuous or intermittent swimming with hesperidin supplementation lowered total cholesterol (-16%, p < .05), LDL-C (-50%, p < 0.05) and triglycerides (-19%, p < 0.05), and increased HDL-C (48%, p < .05). Furthermore, hesperidin enhanced the antioxidant capacity on the continuous swimming group (183%, p < .05) and lowered the lipid peroxidation on the interval swimming

  8. Effects of high-intensity swimming training on the bones of ovariectomized rats

    PubMed Central

    Oh, Taewoong; Tanaka, Sakura; Naka, Tatsuki; Igawa, Shoji

    2016-01-01

    [Purpose] This study was performed to assess the effects of high-intensity intermittent swimming training(HIT) on bone in ovariectomized rats. [Methods] Six-week-old female Sprague-Dawley rats were randomly assigned to either sham operation or bilateral ovariectomy. After surgery, they were divided into the following four groups: 1) sham-operated sedentary (S), 2) sham-operated exercise training (SE), 3) OVX sedentary (O), 4) OVX exercise training (OE) 5) OVX given 17β-estradiol (OE2) and 6) OVX exercise training and given 17β-estradiol (OEE). SE, OE and OEE rats were used extremely high-intensity swim exercise. The rats repeated fourteen 20-s swimming bouts with a weight equivalent to 14, 15, and 16% of body weight for the first 5, the next 9, and the last 5 days, respectively. Between exercise bouts, a 10-s pause was allowed. HIT was originally designed as an exercise method; a method that very quickly induces an increase in the maximum oxygen intake (Tabata I et al., 1996). OEE and OE2 rats were subcutaneously injected ethanol with 25μg/kg body weight 17β-estradiol 3 times per week. [Results] Bone strength, bone mineral density and trabecular bone parameters were measured after a 8-weeks experimental period. Bone strength was significantly higher in the SE, OE, OE2 and OEE group compared with the O group. BV/TV was significant increase in the SE, OE groups compared with the O group. BMD showed no difference in the OE group compared with the O group. [Conclusion] This study demonstrate some beneficial effects of postmenopausal osteoporosis of high-intensity intermittent swimming training on bone structure and strength. PMID:27757386

  9. Resistance to the development of stress-induced behavioral despair in the forced swim test associated with elevated hippocampal Bcl-xl expression.

    PubMed

    Shishkina, Galina T; Kalinina, Tatyana S; Berezova, Inna V; Bulygina, Veta V; Dygalo, Nikolay N

    2010-12-01

    Stress may predispose individuals toward depression through down-regulation of neurogenesis and increase in apoptosis in the brain. However, many subjects show high resistance to stress in relation to psychopathology. In the present study, we assessed the possibility that individual-specific patterns of gene expression associated with cell survival and proliferation may be among the molecular factors underlying stress resilience. Brain-derived neurotrophic factor (BDNF), anti-apoptotic B cell lymphoma like X (Bcl-xl) and pro-apoptotic bcl2-associated X protein (Bax) expression were determined in the hippocampus and frontal cortex of rats naturally differed in despair-like behavior in the forced swim test. In the hippocampus, BDNF messenger RNA (mRNA) level was significantly down-regulated 2h after the forced swim test exposure, and at this time point, Bcl-xl mRNA and protein levels were significantly higher in stressed than in untested animals. The ratios of hippocampal Bcl-xl to Bax mRNA negatively correlated with the total time spent immobile in the test. When animals were divided in two groups according to immobility responses in two consecutive swim sessions and designated as stress resilient if their immobility time did not increase in the second session as it did in stress sensitive rats, it was found that resilient rats had significantly higher Bcl-xl/Bax ratios in the hippocampus than stress sensitive animals. The data suggest that naturally occurring variations in the Bcl-xl/Bax ratio in the hippocampus may contribute to individual differences in vulnerability to stress-induced depression-like behaviors.

  10. Additive effect of lithium and clonidine with 5-HT1A agonists in the forced swimming test.

    PubMed

    Hascoet, M; Bourin, M; Khimake, S

    1994-03-01

    1. The aim of the present work was to demonstrate the possible additive effect of lithium and clonidine with 5-HT1a agonists in the forced swimming test. 2. Anti-depressant like effects of 5-HT1a agonists was investigated using forced swimming test. When administered alone, only 8-OH-DPAT reduced the immobility time in mice. 3. 5-HT1a agonists were then tested in combination with clonidine or lithium. Only gepirone and ipsapirone pretreated by either lithium or clonidine reduced immobility time in the forced swimming test. 4. The authors conclude that lithium and clonidine might be useful to predict antidepressant-like activity of new compounds.

  11. The cardiovascular and endocrine responses to voluntary and forced diving in trained and untrained rats

    PubMed Central

    DiNovo, Karyn. M.; Connolly, Tiffanny M.

    2010-01-01

    The mammalian diving response, consisting of apnea, bradycardia, and increased total peripheral resistance, can be modified by conscious awareness, fear, and anticipation. We wondered whether swim and dive training in rats would 1) affect the magnitude of the cardiovascular responses during voluntary and forced diving, and 2) whether this training would reduce or eliminate any stress due to diving. Results indicate Sprague-Dawley rats have a substantial diving response. Immediately upon submersion, heart rate (HR) decreased by 78%, from 453 ± 12 to 101 ± 8 beats per minute (bpm), and mean arterial pressure (MAP) decreased 25%, from 143 ± 1 to 107 ± 5 mmHg. Approximately 4.5 s after submergence, MAP had increased to a maximum 174 ± 3 mmHg. Blood corticosterone levels indicate trained rats find diving no more stressful than being held by a human, while untrained rats find swimming and diving very stressful. Forced diving is stressful to both trained and untrained rats. The magnitude of bradycardia was similar during both voluntary and forced diving, while the increase in MAP was greater during forced diving. The diving response of laboratory rats, therefore, appears to be dissimilar from that of other animals, as most birds and mammals show intensification of diving bradycardia during forced diving compared with voluntary diving. Rats may exhibit an accentuated antagonism between the parasympathetic and sympathetic branches of the autonomic nervous system, such that in the autonomic control of HR, parasympathetic activity overpowers sympathetic activity. Additionally, laboratory rats may lack the ability to modify the degree of parasympathetic outflow to the heart during an intense cardiorespiratory response (i.e., the diving response). PMID:19923359

  12. Effect of swimming exercise and ethanol on rat liver P450-dependent monooxygenases.

    PubMed

    Ardies, C M; Zachman, E K; Koehn, B J

    1994-12-01

    The interactive effects of 6 wk of repeated swimming exercise and chronic ethanol consumption (36% of total calories) on the hepatic cytochrome P450-dependent monooxygenase system were studied utilizing four groups of male rats in a 2 x 2 factorial design. The sedentary-control (S/C), sedentary-ethanol (S/E), and swim-control (SW/C) groups received the same amount of food that the swim-ethanol (SW/E) group consumed. The swimming groups were trained to swim for 2 h.d-1, 5 d.wk-1. Significant main effects due to ethanol (P < 0.002) and exercise (P < 0.02) were observed for the enhanced cytochrome P450 content and cytochrome P450 reductase activity, respectively. In addition, significant main effects for ethanol (P < 0.001), exercise (P < 0.0001), and significant interaction effects (P < 0.005) on aniline p-hydroxylase activity and significant main effects for ethanol (P < 0.01), exercise (P < 0.01), and interaction effects (P < 0.04) on 7-ethoxycoumarin o-deethylase activity were observed. Because the SW/C treatment had no effect on any of the measured cytochrome P450 activities and the SW/E treatment enhanced P450 activities much more than the S/E treatment, the main effects observed for exercise are accounted for by the alterations produced by combining swimming with the ethanol treatment. Based on these results, repeated exercise combined with ethanol consumption produces a synergistic increase in ethanol-inducible cytochrome P450-dependent activities. PMID:7869878

  13. Acute effects of guarana (Paullinia cupana Mart.) on mouse behaviour in forced swimming and open field tests.

    PubMed

    Campos, A R; Barros, A I S; Albuquerque, F A A; M Leal, L K A; Rao, V S N

    2005-05-01

    Guarana, a herbal extract from the seeds of Paullinia cupana Mart. has been evaluated in comparison with caffeine on mouse behaviour in forced swimming and open field tests. Guarana (25 and 50 mg/kg, p.o.) and caffeine (10 and 20 mg/kg, p.o.) each significantly reduced the duration of immobility in the forced swimming test suggesting an antidepressant-like effect in mice. At these doses, neither substance affected ambulation in the open field test. However, a high dose of guarana (100 mg/kg) and caffeine (30 mg/kg) significantly enhanced the locomotor activity in the open field test. Caffeine, but not guarana, could effectively block an adenosine agonist, cyclopentyl adenosine (CPA)-induced increase in swimming immobility suggesting that mechanism(s) other than the adenosinergic mechanism are involved in the antidepressant-like activity of guarana.

  14. Effect of swimming session duration and repetition on metabolic markers in rats.

    PubMed

    Sampaio-Barros, M M; Farias-Silva, E; Grassi-Kassisse, D M; Spadari-Bratfisch, R C

    2003-06-01

    The aim of this study was to investigate the profile of metabolites in male rats subjected to 50-60 min of swimming on three protocols: group A, a single 50 min swimming session; group B, one session a day for three days (5 min on day 1, 15 min on day 2 and 30 min on day 3); and group C, one session a day for 5 days, with increasing duration from 5 min on day 1, 15, 30, 45 and 60 min on consecutive days. The interval between sessions was 24 h. Measurements were made after the last swimming session. Controls did not swim. The glycogen content of liver and gastrocnemius and soleus muscle was depleted in the three groups that swam, but blood glucose concentration was significantly increased only in group B. Serum lactate concentrations were greater than the controls in groups A and B. There were significant increases in serum free fatty acid concentrations in all groups that swam. The increases in plasma free fatty acids may have resulted from lipolysis stimulated by endogenous catecholamines in groups A and C, since basal lipolysis measured in vitro was unchanged by swimming. The large increase in basal lipolysis in group B may have contributed to the rise in plasma free fatty acids. Adipocytes from rats in groups A and B were supersensitive to epinephrine, whereas those from group C were not. We conclude that the metabolic alterations were less pronounced after the last of five swimming sessions over 5 days than after a single session, even though session duration and the contribution of the physical component were similar. Glucose mobilization, but probably not utilization, was similar in the three groups that swam. The mechanisms of lipid mobilization from adipose tissue differed, depending on the stress paradigm. The metabolic changes in groups A and B indicated that three daily swimming sessions were insufficient to cause adaptation. The results contrast with previous findings for foot-shock stress, which leads to sensitization rather than adaptation in response

  15. Persistence of behaviours in the Forced Swim Test in 3xTg-AD mice at advanced stages of disease.

    PubMed

    Torres-Lista, Virginia; Giménez-Llort, Lydia

    2014-07-01

    Forced Swimming Test (FST) models behavioural despair in animals by loss of motivation to respond or the refusal to escape. The present study characterizes the behavioural responses of 12-month-old male 3xTg-AD mice in FST as compared to age-matched no-transgenic (NTg) mice. Paradoxical results were consistently found from what would be expected from their BPSD (Behavioural and Psychological Symptoms of Dementia)-like profile. The comprehensive analysis of the ethogram shown in the FST considered the intervals of the test (0-2 and 2-6min), all the elicited behavioural responses (immobility, swimming and climbing) and their features (total duration, frequency of episodes and mean duration). Both genotypes showed equal number of swimming episodes and climbing attempts during the first interval, that resulted in high swimming times, short climbing and scarce immobility. Thereafter, the NTg mice showed a behavioural shift over time and the immobility response showed up. In contrast, all the measures consistently evidenced that 3xTg-AD persisted with the previous behavioural pattern. Genotype differences consisted in less number of episodes of immobility and swimming, and a low immobility time in favour of swimming. No differences were found in 'climbing' attempts. The behavioural response observed is discussed as a lack of ability of 3xTg-AD mice to shift behaviour over time that may result of poorest cognitive flexibility and copying with stress strategies more than behavioural despair per se.

  16. A proposal of decision tree to screen putative antidepressants using forced swim and tail suspension tests.

    PubMed

    Bourin, Michel; Chenu, Franck; Ripoll, Nadège; David, Denis Joseph Paul

    2005-11-01

    Interstrain mice variability in response to antidepressant drugs has been reported in the most commonly utilized behavioural animal models of depression: the tail suspension test (TST) and the forced swimming test (FST). The behaviour of mice was examined in both tests for screening various antidepressants with different biochemical mechanism of action. Previous studies have revealed that drug sensitivity depends on the strain and test used. Swiss mice is the most sensitive strain to detect serotonin and/or noradrenaline antidepressants whereas C57BL/6J was the only strain sensitive to bupropion (dopaminergic agent) using the FST. In the TST, all antidepressants studied decreased the immobility time in Swiss and C57BL/6J strains. Detection of an antidepressant-like activity could be performed using only one test (TST with Swiss mice or FST with Swiss and C57Bl/6 Rj mice), but both tests are necessary to conclude on the mechanism of action.

  17. Variability in measurement of swimming forces: a meta-analysis of passive and active drag.

    PubMed

    Havriluk, Rod

    2007-03-01

    An analysis was conducted to identify sources of true and error variance in measuring swimming drag force to draw valid conclusions about performance factor effects. Passive drag studies were grouped according to methodological differences: tow line in pool, tow line in flume, and carriage in tow tank. Active drag studies were grouped according to the theoretical basis: added and/or subtracted drag (AAS), added drag with equal power assumption (AAE), and no added drag (ANA). Data from 36 studies were examined using frequency distributions and meta-analytic procedures. It was concluded that two active methods (AAE and ANA) had sources of systematic error and that one active method (AAS) measured an effect that was different from that measured by passive methods. Consistency in drag coefficient (Cd) values across all three passive methods made it possible to determine the effects of performance factors.

  18. Long-term effects of microgravity on the swimming behaviour of young rats.

    PubMed

    Walton, Kerry D; Benavides, Louis; Singh, Neeraj; Hatoum, Nagi

    2005-06-01

    The postnatal development of sensory systems has been shown in studies over the last four decades to be influenced by experience during critical periods of development. We report here that similar experience-dependent development can be observed in the swimming behaviour of young rats reared from postnatal day 14 (P14) to P30 in the reduced gravitational field of low earth orbit. Animals flown in space when placed in the water on the day of landing maintained their head and forelimbs in a balanced posture. However, until the animals began to swim, their hindquarters showed little lateral postural control resulting in rotation about the longitudinal axis (60 degrees+/-4 deg). Such results suggest an 'unlinking' of postural control of the forequarters from the hindquarters in the early hours after landing. Similar instability seen in animals age-matched to the day of launch (97+/-7 deg) and in ground control animals (9+/-3 deg) was corrected within one or two rotations, even in the absence of swimming. Animals flown in space began to swim sooner after being placed in the water, and the duration of swimming strokes was shorter than in control animals. Motion analysis revealed a difference in the swimming style on landing day. In flight animals, the knee joint was more flexed throughout the stroke, there was a narrower range of movement, and the linear velocity of the tip of the foot was faster throughout most of the stroke than in age-matched control animals. Thus, posture in the water as well as swimming speed and style were altered in the animals flown in space. Some of these characteristics persisted for as long as the animals were followed (30 days). These included the short pre-swimming interval and short stroke duration in flight animals. These findings clearly show that an altered gravitational field influences the postnatal development of motor function. The nature of the differences between animals reared in space for 16 days and those remaining on the ground

  19. Long-term effects of microgravity on the swimming behaviour of young rats

    PubMed Central

    Walton, Kerry D; Benavides, Louis; Singh, Neeraj; Hatoum, Nagi

    2005-01-01

    The postnatal development of sensory systems has been shown in studies over the last four decades to be influenced by experience during critical periods of development. We report here that similar experience-dependent development can be observed in the swimming behaviour of young rats reared from postnatal day 14 (P14) to P30 in the reduced gravitational field of low earth orbit. Animals flown in space when placed in the water on the day of landing maintained their head and forelimbs in a balanced posture. However, until the animals began to swim, their hindquarters showed little lateral postural control resulting in rotation about the longitudinal axis (60°± 4 deg). Such results suggest an ‘unlinking’ of postural control of the forequarters from the hindquarters in the early hours after landing. Similar instability seen in animals age-matched to the day of launch (97 ± 7 deg) and in ground control animals (9 ± 3 deg) was corrected within one or two rotations, even in the absence of swimming. Animals flown in space began to swim sooner after being placed in the water, and the duration of swimming strokes was shorter than in control animals. Motion analysis revealed a difference in the swimming style on landing day. In flight animals, the knee joint was more flexed throughout the stroke, there was a narrower range of movement, and the linear velocity of the tip of the foot was faster throughout most of the stroke than in age-matched control animals. Thus, posture in the water as well as swimming speed and style were altered in the animals flown in space. Some of these characteristics persisted for as long as the animals were followed (30 days). These included the short pre-swimming interval and short stroke duration in flight animals. These findings clearly show that an altered gravitational field influences the postnatal development of motor function. The nature of the differences between animals reared in space for 16 days and those remaining on the ground

  20. Acute Aerobic Swimming Exercise Induces Distinct Effects in the Contractile Reactivity of Rat Ileum to KCl and Carbachol

    PubMed Central

    Araujo, Layanne C. da Cunha; de Souza, Iara L. L.; Vasconcelos, Luiz H. C.; Brito, Aline de Freitas; Queiroga, Fernando R.; Silva, Alexandre S.; da Silva, Patrícia M.; Cavalcante, Fabiana de Andrade; da Silva, Bagnólia A.

    2016-01-01

    Aerobic exercise promotes short-term physiological changes in the intestinal smooth muscle associated to the ischemia-reperfusion process; however, few studies have demonstrated its effect on the intestinal contractile function. Thus, this work describes our observations regarding the influence of acute aerobic swimming exercise in the contractile reactivity, oxidative stress, and morphology of rat ileum. Wistar rats were divided into sedentary (SED) and acutely exercised (EX-AC) groups. Animals were acclimated by 10, 10, and 30 min of swimming exercise in intercalated days 1 week before exercise. Then they were submitted to forced swimming for 1 h with a metal of 3% of their body weight attached to their body. Animals were euthanized immediately after the exercise section and the ileum was suspended in organ baths for monitoring isotonic contractions. The analysis of lipid peroxidation was performed in order to determinate the malondialdehyde (MDA) levels as a marker of oxidative stress, and intestinal smooth muscle morphology by histological staining. Cumulative concentration-response curves to KCl were altered in the EX-AC with an increase in both its efficacy and potency (Emax = 153.2 ± 2.8%, EC50 = 1.3 ± 0.1 × 10−2 M) compared to the SED group (Emax = 100%, EC50 = 1.8 ± 0.1 × 10−2 M). Interestingly, carbachol had its efficacy and potency reduced in the EX-AC (Emax = 67.1 ± 1.4%, EC50 = 9.8 ± 1.4 × 10−7 M) compared to the SED group (Emax = 100%, EC50 = 2.0 ± 0.2 × 10−7 M). The exercise did not alter the MDA levels in the ileum (5.4 ± 0.6 μ mol/mL) in the EX-AC compared to the SED group (8.4 ± 1.7 μ mol/mL). Moreover, neither the circular nor the longitudinal smooth muscle layers thickness were modified by the exercise (66.2 ± 6.0 and 40.2 ± 2.6 μm, respectively), compared to the SED group (61.6 ± 6.4 and 34.8 ± 3.7 μm, respectively). Therefore, the ileum sensitivity to contractile agents is differentially altered by the acute aerobic

  1. Enhancement of the anti-immobility action of antidepressants by risperidone in the forced swimming test in mice.

    PubMed

    Rogóż, Zofia; Kabziński, Marcin

    2011-01-01

    The aim of the present study was to examine the effect of antidepressants (ADs) belonging to different pharmacological groups and risperidone (an atypical antipsychotic drug), given separately or jointly, on immobility time in the forced swimming test in male C57BL/6J mice. The antidepressants: citalopram, fluvoxamine, sertraline, reboxetine, milnacipran (5 and 10 mg/kg), or risperidone in low doses (0.05 and 0.1 mg/kg) given alone did not change the immobility time of mice in the forced swimming test. Co-treatment with reboxetine or milnacipran (10 mg/kg) and risperidone in a lower dose of 0.05 mg/kg or with sertraline, reboxetine (5 and 10 mg/kg), citalopram, fluvoxamine, milnacipran (10 mg/kg) and risperidone in a higher dose of 0.1 mg/kg produced antidepressant-like effect in the forced swimming test. WAY100635 (a 5-HT(1A) receptor antagonist) inhibited the effects induced by co-administration of ADs and risperidone. Active behavior in the forced swimming test was not a consequence of an increased general activity, since the combined treatment with ADs and risperidone failed to enhance the locomotor activity of mice. The obtained results indicate that a low dose of risperidone enhances the activity of ADs in an animal model of depression, and that, among other mechanisms, 5-HT(1A) receptors may play a role in these effects. PMID:22358101

  2. Enhancement of the anti-immobility action of antidepressants by risperidone in the forced swimming test in mice.

    PubMed

    Rogóż, Zofia; Kabziński, Marcin

    2011-01-01

    The aim of the present study was to examine the effect of antidepressants (ADs) belonging to different pharmacological groups and risperidone (an atypical antipsychotic drug), given separately or jointly, on immobility time in the forced swimming test in male C57BL/6J mice. The antidepressants: citalopram, fluvoxamine, sertraline, reboxetine, milnacipran (5 and 10 mg/kg), or risperidone in low doses (0.05 and 0.1 mg/kg) given alone did not change the immobility time of mice in the forced swimming test. Co-treatment with reboxetine or milnacipran (10 mg/kg) and risperidone in a lower dose of 0.05 mg/kg or with sertraline, reboxetine (5 and 10 mg/kg), citalopram, fluvoxamine, milnacipran (10 mg/kg) and risperidone in a higher dose of 0.1 mg/kg produced antidepressant-like effect in the forced swimming test. WAY100635 (a 5-HT(1A) receptor antagonist) inhibited the effects induced by co-administration of ADs and risperidone. Active behavior in the forced swimming test was not a consequence of an increased general activity, since the combined treatment with ADs and risperidone failed to enhance the locomotor activity of mice. The obtained results indicate that a low dose of risperidone enhances the activity of ADs in an animal model of depression, and that, among other mechanisms, 5-HT(1A) receptors may play a role in these effects.

  3. Prior swimming exercise favors muscle recovery in adult female rats after joint immobilization.

    PubMed

    Petrini, Ana Claudia; Ramos, Douglas Massoni; Gomes de Oliveira, Luana; Alberto da Silva, Carlos; Pertille, Adriana

    2016-07-01

    [Purpose] To evaluate the efficacy of pre-exercise on immobilization and subsequent recovery of white gastrocnemius (WG) and soleus (SOL) muscles of female rats. [Subjects and Methods] Thirty, 8-month-old, female Wistar rats were randomly and evenly allocated to six groups: sedentary (S); immobilized sedentary (IS); immobilized/rehabilitated sedentary (IRS); trained (T); immobilized trained (IT); and immobilized/rehabilitated trained (IRT). For four months, T, IT and IRT group animals performed swimming exercise (three sessions per week, 60 minutes per session), while S, IS and IRS groups animals remained housed in cages. After this period, the left hindlimb of the animals from the IS, IRS, IT and IRT groups was immobilized for five days, with the ankle at 90°. After removal of the orthosis, animals from the IRS and IRT groups followed a rehabilitation program based on swimming (five sessions per week, 60 minutes per session) for two weeks. [Results] Immobilization significantly reduced the cross-sectional area of the white gastrocnemius muscle; no changes were observed in the soleus muscles of the trained animals. Transforming growth factor-β1 protein levels were similar among the trained groups. [Conclusion] Prior swimming prevents hypotrophy of the soleus muscle after immobilization, and protein levels reflected the adaptive capacity of the skeletal muscle. PMID:27512267

  4. Prior swimming exercise favors muscle recovery in adult female rats after joint immobilization

    PubMed Central

    Petrini, Ana Claudia; Ramos, Douglas Massoni; Gomes de Oliveira, Luana; Alberto da Silva, Carlos; Pertille, Adriana

    2016-01-01

    [Purpose] To evaluate the efficacy of pre-exercise on immobilization and subsequent recovery of white gastrocnemius (WG) and soleus (SOL) muscles of female rats. [Subjects and Methods] Thirty, 8-month-old, female Wistar rats were randomly and evenly allocated to six groups: sedentary (S); immobilized sedentary (IS); immobilized/rehabilitated sedentary (IRS); trained (T); immobilized trained (IT); and immobilized/rehabilitated trained (IRT). For four months, T, IT and IRT group animals performed swimming exercise (three sessions per week, 60 minutes per session), while S, IS and IRS groups animals remained housed in cages. After this period, the left hindlimb of the animals from the IS, IRS, IT and IRT groups was immobilized for five days, with the ankle at 90°. After removal of the orthosis, animals from the IRS and IRT groups followed a rehabilitation program based on swimming (five sessions per week, 60 minutes per session) for two weeks. [Results] Immobilization significantly reduced the cross-sectional area of the white gastrocnemius muscle; no changes were observed in the soleus muscles of the trained animals. Transforming growth factor-β1 protein levels were similar among the trained groups. [Conclusion] Prior swimming prevents hypotrophy of the soleus muscle after immobilization, and protein levels reflected the adaptive capacity of the skeletal muscle. PMID:27512267

  5. Modafinil facilitates performance on a delayed nonmatching to position swim task in rats.

    PubMed

    Ward, Christopher P; Harsh, John R; York, Kaki M; Stewart, Krista L; McCoy, John G

    2004-08-01

    Modafinil is a wake-promoting drug approved by the FDA for the treatment of narcolepsy. Recent evidence suggests that modafinil may improve learning and memory processes. To further evaluate possible cognitive properties associated with modafinil, male Sprague-Dawley rats were tested in a delayed nonmatching to position (DNMTP) task. A modified water maze allowed animals to make one of two choices for the location of the escape platform. Each trial consisted of two swims. On the information swim (IS), only one choice was open to the animal for escape. One minute later, a choice swim (CS) presented the animal with two choices with the escape platform in the opposite position. There were 10 trials per day for 10 days. Rats received 0, 30, 55, or 100 mg/kg ip of modafinil 30 min prior to testing. Locomotor activity was also assessed. Animals that received 55 and 100 mg/kg made significantly more correct choices, indicating that higher doses of modafinil learned the task faster than did controls. While animals that received 100 mg/kg did exhibit an enhancement of locomotor activity, this effect did not result in more efficient goal-directed behavior. The evidence is consistent with previous research showing that modafinil facilitates cognitive processes.

  6. NMDA GluN2B receptors involved in the antidepressant effects of curcumin in the forced swim test.

    PubMed

    Zhang, Lin; Xu, Tianyuan; Wang, Shuang; Yu, Lanqing; Liu, Dexiang; Zhan, Renzhi; Yu, Shu Yan

    2013-01-10

    The antidepressant-like effect of curcumin, a major active component of Curcuma longa, has been previously demonstrated in the forced swimming test. However, the mechanism of this beneficial effect on immobility scores, which is used to evaluate antidepressants, remains largely uncharacterized. The present study attempts to investigate the effects of curcumin on depressive-like behavior with a focus upon the possible contribution of N-methyl-D-aspartate (NMDA) subtype glutamate receptors in this antidepressant-like effect of curcumin. Male mice were pretreated with specific receptor antagonists to different NMDA receptor subtypes such as CPP, NVP-AAM077 and Ro25-6981 as well as to a partial NMDA receptor agonist, D-cycloserine (DCS), prior to administration of curcumin to observe the effects on depressive behavior as measured by immobility scores in the forced swim test. We found that pre-treatment of mice with CPP, a broad-spectrum competitive NMDA receptor antagonist, blocked the anti-immobility effect of curcumin, suggesting the involvement of the glutamate-NMDA receptors. While pretreatment with NVP-AAM077 (the GluN2A-preferring antagonist) did not affect the anti-immobility effect of curcumin, Ro25-6981 (the GluN2B-preferring antagonist) was found to prevent the effect of curcumin in the forced swimming test. Furthermore, pre-treatment with a sub-effective dose of DCS potentiated the anti-immobility effect of a sub-effective dose of curcumin in the forced swimming test. Taken together, these results suggest that curcumin shows antidepressant-like effects in mice and the activation of GluN2B-containing NMDARs is likely to play a predominate role in this beneficial effect. Therefore, the antidepressant-like effect of curcumin in the forced swim test may be mediated, at least in part, by the glutamatergic system.

  7. Swim stress activates serotonergic and nonserotonergic neurons in specific subdivisions of the rat dorsal raphe nucleus in a temperature-dependent manner.

    PubMed

    Kelly, K J; Donner, N C; Hale, M W; Lowry, C A

    2011-12-01

    Physical (exteroceptive) stimuli and emotional (interoceptive) stimuli are thought to influence stress-related physiologic and behavioral responses through different neural mechanisms. Previous studies have demonstrated that stress-induced activation of brainstem serotonergic systems is influenced by environmental factors such as temperature. In order to further investigate the effects of environmental influences on stress-induced activation of serotonergic systems, we exposed adult male Wistar rats to either home cage control conditions or a 15-min swim in water maintained at 19 °C, 25 °C, or 35 °C and conducted dual immunohistochemical staining for c-Fos, a marker of immediate-early nuclear activation, and tryptophan hydroxylase (TPH), a marker of serotonergic neurons. Changes in core body temperature were documented using biotelemetry. As expected, exposure to cold (19 °C) swim, relative to warm (35 °C) swim, increased c-Fos expression in the external lateral part of the parabrachial nucleus (LPBel), an important part of the spinoparabrachial pathway involved in sensation of cold, cutaneous stimuli, and in serotonergic neurons in the raphe pallidus nucleus (RPa), an important part of the efferent mechanisms controlling thermoregulatory warming responses. In addition, exposure to cold (19 °C) swim, relative to 35 °C swim, increased c-Fos expression in the dorsal raphe nucleus, ventrolateral part/periaqueductal gray (DRVL/VLPAG) and dorsal raphe nucleus, interfascicular part (DRI). Both of these subregions of the dorsal raphe nucleus (DR) have previously been implicated in thermoregulatory responses. Altogether, the data are consistent with the hypothesis that midbrain serotonergic neurons, possibly via activation of afferents to the DR by thermosensitive spinoparabrachial pathways, play a role in integration of physiologic and behavioral responses to interoceptive stress-related cues involved in forced swimming and exteroceptive cues related to cold

  8. The Louisville Swim Scale: A Novel Assessment of Hindlimb Function following Spinal Cord Injury in Adult Rats

    PubMed Central

    Smith, Rebecca R.; Burke, Darlene A.; Baldini, Angela D.; Shum-Siu, Alice; Baltzley, Ryan; Bunger, Michelle; Magnuson, David S.K.

    2010-01-01

    The majority of animal studies examining the recovery of function following spinal cord injury use the BBB Open-Field Locomotor Scale as a primary outcome measure. However, it is now well known that rehabilitation strategies can bring about significant improvements in hindlimb function in some animal models. Thus, improvements in walking following spinal cord injury in rats may be influenced by differences in activity levels and housing conditions during the first few weeks post-injury. Swimming is a natural form of locomotion that animals are not normally exposed to in the laboratory setting. We hypothesized that deficits in, and functional recovery of, swimming would accurately represent the locomotor capability of the nervous system in the absence of any retraining effects. To test this hypothesis, we have compared the recovery of walking and swimming in rats following a range of standardized spinal cord injuries and two different retraining strategies. In order to assess swimming, we developed a rating system we call the Louisville Swimming Scale (LSS) that evaluates three characteristics of swimming that are highly altered by spinal cord injury— namely, hindlimb movement, forelimb dependency, and body position. The data indicate that the LSS is a sensitive and reliable method of determining swimming ability and the improvement in hindlimb function after standardized contusion injury of the thoracic spinal cord. Furthermore, the data suggests that when used in conjunction with the BBB Open-field Locomotor Scale, the LSS assesses locomotor capabilities that are not influenced by a retraining effect. PMID:17115911

  9. Effects of treadmill running on mid-term memory and swim speed in the rat with Morris water maze test.

    PubMed

    Alaei, HojjatAllah; Moloudi, Rohallah; Sarkaki, Ali Reza

    2008-01-01

    Previous studies involving exercise and memory showed that learning and memory were improved by exercise. This study was performed to find the effect of treadmill running on memory. Mid-term memory and swim speed were measured within 8 days. Twenty rats were divided into two groups, a control and a test group. Mid-term memory and swim speed were measured in the Morris water maze apparatus. Our results showed that treadmill running produced a significant enhancement on mid-term memory and swim speed in the test group, which may be mediated by specific molecular pathways.

  10. Antidepressant-like effects of psoralidin isolated from the seeds of Psoralea Corylifolia in the forced swimming test in mice.

    PubMed

    Yi, Li-Tao; Li, Yu-Cheng; Pan, Ying; Li, Jian-Mei; Xu, Qun; Mo, Shi-Fu; Qiao, Chun-Feng; Jiang, Fu-Xin; Xu, Hong-Xi; Lu, Xiao-Bo; Kong, Ling-Dong; Kung, Hsiang-Fu

    2008-02-15

    The antidepressant-like effects of psoralidin isolated from the seeds of Psoralea corylifolia were investigated in the forced swimming test (FST) in ICR strain of male mice. Psoralidin significantly decreased immobility time and increased swimming behavior without altering climbing behavior in the mouse FST after oral administration for 1 h or 3 consecutive days. Psoralidin did not affect locomotor activity in the open-field test. After a 3-day treatment, psoralidin significantly increased 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in various brain regions, as well as, changed dopamine (DA) levels in striatum in mice exposed to FST. Psoralidin also ameliorated the elevations in serum corticotropin-releasing factor (CRF), adrenal corticotropin-releasing hormone (ACTH) and corticosterone concentrations induced by swimming stress in mice. These results suggested that psoralidin possessed potent antidepressant-like properties that were mediated via the monoamine neurotransmitter and the hypothalamic-pituitary-adrenal (HPA) axis systems.

  11. Propulsive force calculations in swimming frogs. II. Application of a vortex ring model to DPIV data.

    PubMed

    Stamhuis, Eize J; Nauwelaerts, Sandra

    2005-04-01

    Frogs propel themselves by kicking water backwards using a synchronised extension of their hind limbs and webbed feet. To understand this propulsion process, we quantified the water movements and displacements resulting from swimming in the green frog Rana esculenta, applying digital particle image velocimetry (DPIV) to the frog's wake. The wake showed two vortex rings left behind by the two feet. The rings appeared to be elliptic in planform, urging for correction of the observed ring radii. The rings' long and short axes (average ratio 1.75:1) were about the same size as the length and width of the propelling frog foot and the ellipsoid mass of water accelerated with it. Average thrust forces were derived from the vortex rings, assuming all propulsive energy to be compiled in the rings. The calculated average forces (F(av)=0.10+/-0.04 N) were in close agreement with our parallel study applying a momentum-impulse approach to water displacements during the leg extension phase. We did not find any support for previously assumed propulsion enhancement mechanisms. The feet do not clap together at the end of the power stroke and no "wedge-action" jetting is observed. Each foot accelerates its own water mantle, ending up in a separate vortex ring without interference by the other leg.

  12. Enhancement of immobility in a forced swimming test by subacute or repeated treatment with phencyclidine: a new model of schizophrenia.

    PubMed Central

    Noda, Y.; Yamada, K.; Furukawa, H.; Nabeshima, T.

    1995-01-01

    1. Immobility induced by forced swimming is well known as an animal model of depression. To develop an animal model for the negative symptoms of schizophrenia, in particular the depressive symptoms, the effect of phencyclidine (PCP) on immobility in the forced swimming test was investigated in mice, since PCP produces such negative symptoms in humans. 2. Repeated treatment with PCP (10 mg kg-1 day-1, s.c., once a day for 14 days) prolonged the immobility time in the forced swimming test 24 h after the final injection compared with saline treatment; the effect was not obtained by single or 5 treatments with PCP (10 mg kg-1, s.c.), or by repeated treatment with methamphetamine (0.5 and 1 mg kg-1 day-1, s.c., once a day for 14 days). 3. The enhancing effect of PCP (10 mg kg-1 day-1, s.c.) on the immobility persisted for at least 21 days after the withdrawal of the drug. 4. Haloperidol (0.3 and 1 mg kg-1, p.o.), ritanserin (3 and 10 mg kg-1, p.o.), risperidone (0.1-1 mg kg-1, p.o.), and clozapine (3 and 10 mg kg-1, p.o.) failed to attenuate the immobility induced by the forced swimming in mice repeatedly treated with saline when the drugs were administered 1 h before the forced swimming test. However, ritanserin (30 mg kg-1) and clozapine (30 mg kg-1) did attenuate this immobility. 5. The enhancing effect of PCP on the immobility was attenuated by ritanserin (3 and 10 mg kg-1, p.o.), risperidone (0.3 mg kg-1, p.o.), and clozapine (3 and 10 mg kg-1, p.o.), whereas haloperidol (0.3 and 1 mg kg-1, p.o.) had no effect. 6. These results suggest that the enhancement of immobility in the forced swimming test brought about by repeated PCP treatment could be used as a model of the negative symptoms, particularly the depression, of schizophrenia. This effect of PCP appeared to be mediated, at least in part, via 5-HT2A receptors. Images Figure 6 Figure 7 PMID:8581295

  13. The forced swimming-induced behavioural immobility response involves histone H3 phospho-acetylation and c-Fos induction in dentate gyrus granule neurons via activation of the N-methyl-D-aspartate/extracellular signal-regulated kinase/mitogen- and stress-activated kinase signalling pathway.

    PubMed

    Chandramohan, Yalini; Droste, Susanne K; Arthur, J Simon C; Reul, Johannes M H M

    2008-05-01

    The hippocampus is involved in learning and memory. Previously, we have shown that the acquisition of the behavioural immobility response after a forced swim experience is associated with chromatin modifications and transcriptional induction in dentate gyrus granule neurons. Given that both N-methyl-D-aspartate (NMDA) receptors and the extracellular signal-regulated kinases (ERK) 1/2 signalling pathway are involved in neuroplasticity processes underlying learning and memory, we investigated in rats and mice whether these signalling pathways regulate chromatin modifications and transcriptional events participating in the acquisition of the immobility response. We found that: (i) forced swimming evoked a transient increase in the number of phospho-acetylated histone H3-positive [P(Ser10)-Ac(Lys14)-H3(+)] neurons specifically in the middle and superficial aspects of the dentate gyrus granule cell layer; (ii) antagonism of NMDA receptors and inhibition of ERK1/2 signalling blocked forced swimming-induced histone H3 phospho-acetylation and the acquisition of the behavioural immobility response; (iii) double knockout (DKO) of the histone H3 kinase mitogen- and stress-activated kinases (MSK) 1/2 in mice completely abolished the forced swimming-induced increases in histone H3 phospho-acetylation and c-Fos induction in dentate granule neurons and the behavioural immobility response; (iv) blocking mineralocorticoid receptors, known not to be involved in behavioural immobility in the forced swim test, did not affect forced swimming-evoked histone H3 phospho-acetylation in dentate neurons; and (v) the pharmacological manipulations and gene deletions did not affect behaviour in the initial forced swim test. We conclude that the forced swimming-induced behavioural immobility response requires histone H3 phospho-acetylation and c-Fos induction in distinct dentate granule neurons through recruitment of the NMDA/ERK/MSK 1/2 pathway.

  14. Evidences that maternal swimming exercise improves antioxidant defenses and induces mitochondrial biogenesis in the brain of young Wistar rats.

    PubMed

    Marcelino, T B; Longoni, A; Kudo, K Y; Stone, V; Rech, A; de Assis, A M; Scherer, E B S; da Cunha, M J; Wyse, A T S; Pettenuzzo, L F; Leipnitz, G; Matté, C

    2013-08-29

    Physical exercise during pregnancy has been considered beneficial to mother and child. Recent studies showed that maternal swimming improves memory in the offspring, increases hippocampal neurogenesis and levels of neurotrophic factors. The objective of this work was to investigate the effect of maternal swimming during pregnancy on redox status and mitochondrial parameters in brain structures from the offspring. Adult female Wistar rats were submitted to five swimming sessions (30 min/day) prior to mating with adult male Wistar rats, and then trained during the pregnancy (five sessions of 30-min swimming/week). The litter was sacrificed when 7 days old, when cerebellum, parietal cortex, hippocampus, and striatum were dissected. We evaluated the production of reactive species and antioxidant status, measuring the activities of superoxide-dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx), as well as non-enzymatic antioxidants. We also investigated a potential mitochondrial biogenesis regarding mitochondrion mass and membrane potential, through cytometric approaches. Our results showed that maternal swimming exercise promoted an increase in reactive species levels in cerebellum, parietal cortex, and hippocampus, demonstrated by an increase in dichlorofluorescein oxidation. Mitochondrial superoxide was reduced in cerebellum and parietal cortex, while nitrite levels were increased in cerebellum, parietal cortex, hippocampus, and striatum. Antioxidant status was improved in cerebellum, parietal cortex, and hippocampus. SOD activity was increased in parietal cortex, and was not altered in the remaining brain structures. CAT and GPx activities, as well as non-enzymatic antioxidant potential, were increased in cerebellum, parietal cortex, and hippocampus of rats whose mothers were exercised. Finally, we observed an increased mitochondrial mass and membrane potential, suggesting mitochondriogenesis, in cerebellum and parietal cortex of pups subjected to

  15. The selective glucocorticoid receptor antagonist CORT 108297 decreases neuroendocrine stress responses and immobility in the forced swim test.

    PubMed

    Solomon, Matia B; Wulsin, Aynara C; Rice, Taylor; Wick, Dayna; Myers, Brent; McKlveen, Jessica; Flak, Jonathan N; Ulrich-Lai, Yvonne; Herman, James P

    2014-04-01

    Pre-clinical and clinical studies have employed treatment with glucocorticoid receptor (GR) antagonists in an attempt to limit the deleterious behavioral and physiological effects of excess glucocorticoids. Here, we examined the effects of GR antagonists on neuroendocrine and behavioral stress responses, using two compounds: mifepristone, a GR antagonist that is also a progesterone receptor antagonist, and CORT 108297, a specific GR antagonist lacking anti-progestin activity. Given its well-documented impact on neuroendocrine and behavioral stress responses, imipramine (tricyclic antidepressant) served as a positive control. Male rats were treated for five days with mifepristone (10mg/kg), CORT 108297 (30mg/kg and 60mg/kg), imipramine (10mg/kg) or vehicle and exposed to forced swim test (FST) or restraint stress. Relative to vehicle, imipramine potently suppressed adrenocorticotropin hormone (ACTH) responses to FST and restraint exposure. Imipramine also decreased immobility in the FST, consistent with antidepressant actions. Both doses of CORT 108297 potently suppressed peak corticosterone responses to FST and restraint stress. However, only the higher dose of CORT 108297 (60mg/kg) significantly decreased immobility in the FST. In contrast, mifepristone induced protracted secretion of corticosterone in response to both stressors, and modestly decreased immobility in the FST. Taken together, the data indicate distinct effects of each compound on neuroendocrine stress responses and also highlight dissociation between corticosterone responses and immobility in the FST. Within the context of the present study, our data suggest that CORT 108297 may be an attractive alternative for mitigating neuroendocrine and behavioral states associated with excess glucocorticoid secretion.

  16. Papaver Rhoeas L. Hydroalcoholic Extract Exacerbates Forced Swimming Test-Induced Depression in Mice

    PubMed Central

    Osanloo, Naser; Najafi-Abedi, Akram; Jafari, Fatemeh; Javid, Farshid; Pirpiran, Mohsen; Memar Jafari, Mohammad-Reza; Mousavi Khosravi, Seyed Ali; Rahimzadeh Behzadi, Mohammad; Ranjbaran, Mina; Sahraei, Hedayat

    2016-01-01

    Introduction: Depression is one of the most frequent psychiatric disorders in the world with occurs with higher incidence in women. In the present study, the effect of water-alcoholic extract of Papaver rhoeas L. on forced swimming test (FST) in Swiss-Webster mice were examined. Methods: We used Swiss-Webster mice (20–25 g) to execute FST on them. The plant extract (1, 10, 30, and 100 mg/kg) was injected to the animals 30 minutes before each session. Fluoxetine (20 mg/kg) was used as standard antidepressant drug. In another group of animals, 30 minutes after extract administration, blood samples were taken from retro-orbital sinus for corticosterone assay. Yet in third group, the drugs were injected to the animals and 30 minutes later, their activities were tested in an open field apparatus. Results: Our experiments showed that the extract efficiently reduced FST time both in male and female mice dose-dependently. This effect was comparable with fluoxetine. In addition, corticosterone assay indicated that plasma corticosterone in animals which received extract was higher than those amounts in fluoxetine and saline controls. Moreover, the animals did not show any motor activity deficit in all doses of the extract and fluoxetine compared to saline control. Conclusion: The extract of Papaver rhoeas can reduce immobility time which is comparable to the effect of fluoxetine. Also the effect of the extract is contrary to its effects on plasma corticosterone level and or animals’ activity. PMID:27563412

  17. Evidence for the involvement of extinction-associated inhibitory learning in the forced swimming test.

    PubMed

    Campus, P; Colelli, V; Orsini, C; Sarra, D; Cabib, S

    2015-02-01

    The forced swimming test (FST) remains one of the most used tools for screening antidepressants in rodent models. Nonetheless, the nature of immobility, its main behavioral measure, is still a matter of debate. The present study took advantage of our recent finding that mice of the inbred DBA/2J strain require a functioning left dorsolateral striatum (DLS) to consolidate long-term memory of FST to test whether immobility is the outcome of stress-related learning. Infusion of the GABA-A agonist muscimol in the left DLS immediately after a single experience of FST prevented and infusion in the left or the right amygdala impaired recall of the acquired levels of immobility in a probe test performed 24h later. Post-training left DLS infusion of muscimol, at a dose capable of preventing retention of FST-induced immobility, did not influence 24h retention of inhibitory avoidance training or of the escape response acquired in a water T-maze. However, this same treatment prevented 24h retention of the extinction training of the consolidated escape response. These results indicate that a left DLS-centered memory system selectively mediates memory consolidation of FST and of escape extinction and support the hypothesis that immobility is the result of extinction-like inhibitory learning involving all available escape responses due to the inescapable/unavoidable nature of FST experience.

  18. Monoamine metabolism changes following the mouse forced swimming test but not the tail suspension test.

    PubMed

    Renard, Caroline E; Dailly, Eric; David, Denis J P; Hascoet, Martine; Bourin, Michel

    2003-08-01

    Microdialysis, binding and behavioural studies have shown that the dopaminergic system plays a role in antidepressant treatment. It has been suggested that stress may provoke a modification in dopamine (DA) release in different brain areas and that the forced swimming test (FST), in its own accord as a stressor, may be responsible for this modification. Naive male Swiss mice, receiving saline solution, were used in two animal models of depression, the FST and the tail suspension test (TST). In order to understand the locomotor aspect of each test, groups of mice were studied for effects on locomotor activity. Following each test, mice were killed by cervical dislocation, brains were removed and concentrations of amines in the whole brain were analysed by high-performance liquid chromatography. DA concentration increased from 5 min of the FST, dihydroxyphénylacetate (DOPAC), from 20 min of FST and serotonin, from 8 min of FST. No modification of noradrenaline was observed during the FST and no modification of the neurotransmitter concentrations was observed during the TST. Following an FST of 2-min duration, a hypolocomotor effect was observed in the subsequent actimeter test. The same effect was observed after a TST of 8 min and onwards. This study confirms the fact that although these two tests are used to study depression, they involve different neuronal mechanisms.

  19. Inhibition of progesterone metabolism mimics the effect of progesterone withdrawal on forced swim test immobility.

    PubMed

    Beckley, Ethan H; Finn, Deborah A

    2007-10-01

    Withdrawal from high levels of progesterone in rodents has been proposed as a model for premenstrual syndrome or postpartum depression. Forced swim test (FST) immobility, used to model depression, was assessed in intact female DBA/2J mice following progesterone withdrawal (PWD) or treatment with the 5alpha-reductase inhibitor finasteride. Following 5 daily progesterone injections (5 mg/kg IP) FST immobility increased only in mice withdrawn for 3 days (p<.05). In another experiment, 3 days of PWD significantly decreased levels of progesterone compared to 0 days of withdrawal, but progesterone levels at 3 days of PWD did not differ from vehicle-treated controls. In a final study, mice received daily injections of progesterone (5 mg/kg IP) for 8 days, with 0 mg/kg, 50 mg/kg, or 100 mg/kg finasteride co-administered for the last three days. Mice that received 100 mg/kg finasteride, but not 50 mg/kg finasteride, displayed increased FST immobility. PWD and finasteride treatment, both of which reduce allopregnanolone levels, were associated with increased FST immobility in female DBA/2J mice. These findings suggest that decreased levels of the GABAergic neurosteroid allopregnanolone contribute to symptoms of PWD. Future studies of PWD may provide information about human conditions that are associated with hormone changes such as premenstrual syndrome or postpartum depression.

  20. Evidences for the agmatine involvement in antidepressant like effect of bupropion in mouse forced swim test.

    PubMed

    Kotagale, Nandkishor R; Tripathi, Sunil J; Aglawe, Manish M; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

    2013-06-01

    Although bupropion has been widely used in the treatment of depression, the precise mechanism of its therapeutic actions is not fully understood. The present study investigated the role of agmatine in an antidepressant like effect of bupropion in mouse forced swim test. The antidepressant like effect of bupropion was potentiated by pretreatment with agmatine (10-20mg/kg, ip) and by the drugs known to increase endogenous agmatine levels in brain viz., l-arginine (40 μg/mouse, icv), an agmatine biosynthetic precursor, ornithine decarboxylase inhibitor, dl-α-difluoromethyl ornithine hydrochloride, DFMO (12.5 μg/mouse, icv), diamine oxidase inhibitor, aminoguanidine (6.5 μg/mouse, icv) and agmatinase inhibitor, arcaine (50 μg/mouse, icv) as well as imidazoline I1 receptor agonists, moxonidine (0.25mg/kg, ip) and clonidine (0.015 mg/kg, ip) and imidazoline I2 receptor agonist, 2-(2-benzofuranyl)-2-imidazoline hydrochloride, 2-BFI (5mg/kg, ip). Conversely, prior administration of I1 receptor antagonist, efaroxan (1mg/kg, ip) and I2 receptor antagonist, idazoxan (0.25mg/kg, ip) blocked the antidepressant like effect of bupropion and its synergistic combination with agmatine. These results demonstrate involvement of agmatine in the antidepressant like effect of bupropion and suggest agmatine and imidazoline receptors as a potential therapeutic target for the treatment of depressive disorders.

  1. Galmic, a nonpeptide galanin receptor agonist, affects behaviors in seizure, pain, and forced-swim tests

    PubMed Central

    Bartfai, Tamas; Lu, Xiaoying; Badie-Mahdavi, Hedieh; Barr, Alasdair M.; Mazarati, Andrey; Hua, Xiao-Ying; Yaksh, Tony; Haberhauer, Gebhard; Ceide, Susana Conde; Trembleau, Laurent; Somogyi, Laszlo; Kröck, Lenz; Rebek, Julius

    2004-01-01

    The pharmacological exploitation of the galanin receptors as drug targets for treatment of epilepsy, depression, and pain has been hampered by the lack of workable compounds for medicinal chemists from random screening of large chemical libraries. The present work uses the tripeptidomimetic galnon and displays its presumed pharmacophores on a rigid molecular scaffold. The scaffold is related to marine natural products and presents three functional groups near one another in space, in a manner reminiscent of a protein surface. An active compound, Galmic, was identified from a small synthetic library and tested in vitro and in vivo for its affinity and efficacy at galanin receptors. Galmic has micromolar affinity for GalR1 receptors (Ki = 34.2 μM) and virtually no affinity for GalR2 receptors. In vitro, Galmic, like galanin, suppresses long-term potentiation in the dentate gyrus; it blocks status epilepticus when injected intrahippocampally or administered i.p. Galmic applied i.p. shows antidepressant-like effects in the forced-swim test, and it is a potent inhibitor of flinching behavior in the inflammatory pain model induced by formalin injection. These data further implicate brain and spinal cord galanin receptors as drug targets and provide an example of a systemically active compound based on a scaffold that mimics protein surfaces. PMID:15240875

  2. No evidence for a bioenergetic advantage from forced swimming in rainbow trout under a restrictive feeding regime.

    PubMed

    Skov, Peter V; Lund, Ivar; Pargana, Alexandre M

    2015-01-01

    Sustained swimming at moderate speeds is considered beneficial in terms of the productive performance of salmonids, but the causative mechanisms have yet to be unequivocally established. In the present study, the effects of moderate exercise on the bioenergetics of rainbow trout were assessed during a 15 week growth experiment, in which fish were reared at three different current speeds: 1 BL s(-1), 0.5 BL s(-1) and still water (≈ 0 BL s(-1)). Randomly selected groups of 100 fish were distributed among twelve 600 L tanks and maintained on a restricted diet regime. Specific growth rate (SGR) and feed conversion ratio (FCR) were calculated from weight and length measurements every 3 weeks. Routine metabolic rate (RMR) was measured every hour as rate of oxygen consumption in the tanks, and was positively correlated with swimming speed. Total ammonia nitrogen (TAN) excretion rates showed a tendency to decrease with increasing swimming speeds, yet neither they nor the resulting nitrogen quotients (NQ) indicated that swimming significantly reduced the fraction of dietary protein used to fuel metabolism. Energetic budgets revealed a positive correlation between energy expenditure and the current speed at which fish were reared, fish that were forced to swim and were fed restrictively consequentially had poorer growth and feed utilization. The results show that for rainbow trout, water current can negatively affect growth despite promoting minor positive changes in substrate utilization. We hypothesize that this may be the result of either a limited dietary energy supply from diet restriction being insufficient for both covering the extra costs of swimming and supporting enhanced growth. PMID:25705195

  3. Interaction between piloting and beacon homing by rats in a swimming pool.

    PubMed

    Redhead, E S; Roberts, A; Good, M; Pearce, J M

    1997-07-01

    In three experiments, rats in a swimming pool were trained to find a submerged platform with a beacon attached to it. For some rats this beacon unambiguously identified the location of the platform; for others the beacon was made ambiguous by placement of an identical beacon in a different part of the pool. Test trials, in the absence of the platform and the beacons, revealed more persistent searching near the original location of the platform if the beacon attached to the platform had been ambiguous. These results show that learning about the location of the platform, with regard to cues that lie beyond the pool, is influenced by the extent to which an animal can find the platform by relying on other cues. The final experiment shows that this interaction between cues is influenced by an animal's prior experience.

  4. Antidepressant-like effects of L-theanine in the forced swim and tail suspension tests in mice.

    PubMed

    Yin, Cui; Gou, Lingshan; Liu, Yi; Yin, Xiaoxing; Zhang, Ling; Jia, Genguang; Zhuang, Xuemei

    2011-11-01

    L-theanine (γ-glutamylethylamide), an amino acid component of green tea, has been shown to reduce mental and physical stress, and to improve memory function. In this study, the antidepressant effect of L-theanine was investigated in mice using the forced swim test, tail suspension test, open-field test and reserpine test. L-theanine produced an antidepressant-like effect, since the administration of L-theanine at doses of 1, 4 and 20 mg/kg for 10 successive days significantly reduced the immobility time in both the forced swim test and tail suspension test, compared with the control group, without accompanying changes in ambulation in the open-field test. Moreover, L-theanine significantly antagonized reserpine-induced ptosis and hypothermia. Taken together, these results indicate that L-theanine possessed an antidepressant-like effect in mice, which may be mediated by the central monoaminergic neurotransmitter system.

  5. Sensitivity during the forced swim test is a key factor in evaluating the antidepressant effects of abscisic acid in mice.

    PubMed

    Qi, Cong-Cong; Shu, Yu-Mian; Chen, Fang-Han; Ding, Yu-Qiang; Zhou, Jiang-Ning

    2016-03-01

    Abscisic acid (ABA), a crucial phytohormone, is distributed in the brains of mammals and has been shown to have antidepressant effects in the chronic unpredictable mild stress test. The forced swim test (FST) is another animal model that can be used to assess antidepressant-like behavior in rodents. Here, we report that the antidepressant effects of ABA are associated with sensitivities to the FST in mice. Based on mean immobility in the 5-min forced swim pre-test, ICR mice were divided into short immobility mice (SIM) and long immobility mice (LIM) substrains. FST was carried out 8 days after drug administration. Learned helplessness, as shown by increased immobility, was only observed in SIM substrain and could be prevented by an 8-day ABA treatment. Our results show that ABA has antidepressant effects in SIM substrain and suggest that mice with learned helplessness might be more suitable for screening potential antidepressant drugs.

  6. Effects of dietary restriction or swimming on lymphocytes and macrophages functionality from old rats.

    PubMed

    Meneguello-Coutinho, Marcela; Caperuto, Erico; Bacurau, Aline Villa Nova; Chamusca, Grabriela; Uchida, Marco Carlos; Tibana, Ramires Alsamir; Pereira, Guilherme Borges; Navalta, James Wilfred; Wasinski, Frederick; Cavaglieri, Claudia Regina; Prestes, Jonato; Costa Rosa, Luis Fernando Bicudo Pereira; Bacurau, Reury Frank

    2014-01-01

    Although aging compromises the functionality of macrophages (MΦ) and lymphocytes (LY), and dietary restriction (DR) and exercise partially counterbalance immunosenescence, it is unknown what effects of both strategies have on the functionality of these immune cells. Rats were randomly distributed into adult control (AD), older group (OLD), older submitted to 50% of DR (DR) and older submitted to swimming (EX) (n = 10 in each group). The function of immune cells (proliferative index, phagocytic capacity and H₂O₂ production), the weight and protein content of lymphoid organs (thymus and spleen), plasma glutamine concentration, interleukins (IL-1, IL-2, IL-6) and, immunoglobulins (IgA and IgG) were analysed. There was an increase of 74% in body weight in aged animals as compared with the AD group, while body weight reduced 19% in the DR as compared with the OLD group. Swimming training stimulated MΦ phagocytosis, while the EX group presented a decrease of the proliferative capacity of LY from the mesenteric lymph nodes (44% and 62%, respectively), when stimulated with ConA and LPS as compared with the old rats. These data demonstrated that DR and exercise affects differentially MΦ and LY function. PMID:24206426

  7. Molecular aspects involved in swimming exercise training reducing anhedonia in a rat model of depression.

    PubMed

    Sigwalt, A R; Budde, H; Helmich, I; Glaser, V; Ghisoni, K; Lanza, S; Cadore, E L; Lhullier, F L R; de Bem, A F; Hohl, A; de Matos, F J; de Oliveira, P A; Prediger, R D; Guglielmo, L G A; Latini, A

    2011-09-29

    Patients suffering from depression frequently display hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) resulting in elevated cortisol levels. One main symptom of this condition is anhedonia. There is evidence that exercise training can be used as a rehabilitative intervention in the treatment of depressive disorders. In this scenario, the aim of the present study was to assess the effect of an aerobic exercise training protocol on the depressive-like behavior, anhedonia, induced by repeated dexamethasone administration. The study was carried out on adult male Wistar rats randomly divided into four groups: the "control group" (C), "exercise group" (E), "dexamethasone group" (D) and the "dexamethasone plus exercise group" (DE). The exercise training consisted of swimming (1 h/d, 5 d/wk) for 3 weeks, with an overload of 5% of the rat body weight. Every day rats were injected with either dexamethasone (D/DE) or saline solution (C/E). Proper positive controls, using fluoxetine, were run in parallel. Decreased blood corticosterone levels, reduced adrenal cholesterol synthesis and adrenal weight (HPA disruption), reduced preference for sucrose consumption and increased immobility time (depressive-like behavior), marked hippocampal DNA oxidation, increased IL-10 and total brain-derived neurotrophic factor (BDNF; pro-plus mature-forms) and a severe loss of body mass characterized the dexamethasone-treated animals. Besides increasing testosterone blood concentrations, the swim training protected depressive rats from the anhedonic state, following the same profile as fluoxetine, and also from the dexamethasone-induced impaired neurochemistry. The data indicate that physical exercise could be a useful tool in preventing and treating depressive disorders.

  8. Does Swimming Exercise Affect Experimental Chronic Kidney Disease in Rats Treated with Gum Acacia?

    PubMed Central

    Ali, Badreldin H.; Al-Salam, Suhail; Al Za'abi, Mohammed; Al Balushi, Khalid A.; Ramkumar, Aishwarya; Waly, Mostafa I.; Yasin, Javid; Adham, Sirin A.; Nemmar, Abderrahim

    2014-01-01

    Different modes of exercise are reported to be beneficial in subjects with chronic kidney disease (CKD). Similar benefits have also been ascribed to the dietary supplement gum acacia (GA). Using several physiological, biochemical, immunological, and histopathological measurements, we assessed the effect of swimming exercise (SE) on adenine –induced CKD, and tested whether SE would influence the salutary action of GA in rats with CKD. Eight groups of rats were used, the first four of which were fed normal chow for 5 weeks, feed mixed with adenine (0.25% w/w) to induce CKD, GA in the drinking water (15% w/v), or were given adenine plus GA, as above. Another four groups were similarly treated, but were subjected to SE during the experimental period, while the first four groups remained sedentary. The pre-SE program lasted for four days (before the start of the experimental treatments), during which the rats were made to swim for 5 to 10 min, and then gradually extended to 20 min per day. Thereafter, the rats in the 5th, 6th, 7th, and 8th groups started to receive their respective treatments, and were subjected to SE three days a week for 45 min each. Adenine induced the typical signs of CKD as confirmed by histopathology, and the other measurements, and GA significantly ameliorated all these signs. SE did not affect the salutary action of GA on renal histology, but it partially improved some of the above biochemical and physiological analytes, suggesting that addition of this mode of exercise to GA supplementation may improve further the benefits of GA supplementation. PMID:25048380

  9. Swimming physiology.

    PubMed

    Holmér, I

    1992-05-01

    Swimming takes place in a medium, that presents different gravitational and resistive forces, respiratory conditions and thermal stress compared to air. The energy cost of propulsion in swimming is high, but a considerable reduction occurs at a given velocity as result of regular swim training. In medley swimmers the energy cost is lowest for front crawl, followed by backstroke, butterfly and breast-stroke. Cardiac output is probably not limiting for performance since swimmers easily achieve higher values during running. Maximal heart rate, however, is lowered by approx. 10 beats/min during swimming compared to running. Most likely active muscle mass is smaller and rate of power production lesser in swimming. Local factors, such as peripheral circulation, capillary density, perfusion pressure and metabolic capacity of active muscles, are important determinants of the power production capacity and emphasize the role of swim specific training movements. Improved swimming technique and efficiency are likely to explain much of the continuous progress in performance. Rational principles based on improved understanding of the biomechanics and physiology of swimming should be guidelines for swimmers and coaches in their efforts to explore the limits of human performance. PMID:1642724

  10. Swimming training attenuates oxidative damage and increases enzymatic but not non-enzymatic antioxidant defenses in the rat brain

    PubMed Central

    Nonato, L.F.; Rocha-Vieira, E.; Tossige-Gomes, R.; Soares, A.A.; Soares, B.A.; Freitas, D.A.; Oliveira, M.X.; Mendonça, V.A.; Lacerda, A.C.; Massensini, A.R.; Leite, H.R.

    2016-01-01

    Although it is well known that physical training ameliorates brain oxidative function after injuries by enhancing the levels of neurotrophic factors and oxidative status, there is little evidence addressing the influence of exercise training itself on brain oxidative damage and data is conflicting. This study investigated the effect of well-established swimming training protocol on lipid peroxidation and components of antioxidant system in the rat brain. Male Wistar rats were randomized into trained (5 days/week, 8 weeks, 30 min; n=8) and non-trained (n=7) groups. Forty-eight hours after the last session of exercise, animals were euthanized and the brain was collected for oxidative stress analysis. Swimming training decreased thiobarbituric acid reactive substances (TBARS) levels (P<0.05) and increased the activity of the antioxidant enzyme superoxide dismutase (SOD) (P<0.05) with no effect on brain non-enzymatic total antioxidant capacity, estimated by FRAP (ferric-reducing antioxidant power) assay (P>0.05). Moreover, the swimming training promoted metabolic adaptations, such as increased maximal workload capacity (P<0.05) and maintenance of body weight. In this context, the reduced TBARS content and increased SOD antioxidant activity induced by 8 weeks of swimming training are key factors in promoting brain resistance. In conclusion, swimming training attenuated oxidative damage and increased enzymatic antioxidant but not non-enzymatic status in the rat brain. PMID:27706439

  11. Subtype-selective nicotinic acetylcholine receptor agonists enhance the responsiveness to citalopram and reboxetine in the mouse forced swim test.

    PubMed

    Andreasen, Jesper T; Nielsen, Elsebet Ø; Christensen, Jeppe K; Olsen, Gunnar M; Peters, Dan; Mirza, Naheed R; Redrobe, John P

    2011-10-01

    Nicotine increases serotonergic and noradrenergic neuronal activity and facilitates serotonin and noradrenaline release. Accordingly, nicotine enhances antidepressant-like actions of reuptake inhibitors selective for serotonin or noradrenaline in the mouse forced swim test and the mouse tail suspension test. Both high-affinity α4β2 and low-affinity α7 nicotinic acetylcholine receptor subtypes are implicated in nicotine-mediated release of serotonin and noradrenaline. The present study therefore investigated whether selective agonism of α4β2 or α7 nicotinic acetylcholine receptors would affect the mouse forced swim test activity of two antidepressants with distinct mechanisms of action, namely the selective serotonin reuptake inhibitor citalopram and the noradrenaline reuptake inhibitor reboxetine. Subthreshold and threshold doses of citalopram (3 and 10 mg/kg) or reboxetine (10 and 20 mg/kg) were tested alone and in combination with the novel α4β2-selective partial nicotinic acetylcholine receptor agonist, NS3956 (0.3 and 1.0 mg/kg) or the α7-selective nicotinic acetylcholine receptor agonist, PNU-282987 (10 and 30 mg/kg). Alone, NS3956 and PNU-282987 were devoid of activity in the mouse forced swim test, but both 1.0 mg/kg NS3956 and 30 mg/kg PNU-282987 enhanced the effect of citalopram and also reboxetine. The data suggest that the activity of citalopram and reboxetine in the mouse forced swim test can be enhanced by agonists at either α4β2 or α7 nicotinic acetylcholine receptors, suggesting that both nicotinic acetylcholine receptor subtypes may be involved in the nicotine-enhanced action of antidepressants.

  12. Computer assisted video analysis of swimming performance in a forced swim test: simultaneous assessment of duration of immobility and swimming style in mice selected for high and low swim-stress induced analgesia.

    PubMed

    Juszczak, Grzegorz R; Lisowski, Paweł; Sliwa, Adam T; Swiergiel, Artur H

    2008-10-20

    In behavioral pharmacology, two problems are encountered when quantifying animal behavior: 1) reproducibility of the results across laboratories, especially in the case of manual scoring of animal behavior; 2) presence of different behavioral idiosyncrasies, common in genetically different animals, that mask or mimic the effects of the experimental treatments. This study aimed to develop an automated method enabling simultaneous assessment of the duration of immobility in mice and the depth of body submersion during swimming by means of computer assisted video analysis system (EthoVision from Noldus). We tested and compared parameters of immobility based either on the speed of an object (animal) movement or based on the percentage change in the object's area between the consecutive video frames. We also examined the effects of an erosion-dilation filtering procedure on the results obtained with both parameters of immobility. Finally, we proposed an automated method enabling assessment of depth of body submersion that reflects swimming performance. It was found that both parameters of immobility were sensitive to the effect of an antidepressant, desipramine, and that they yielded similar results when applied to mice that are good swimmers. The speed parameter was, however, more sensitive and more reliable because it depended less on random noise of the video image. Also, it was established that applying the erosion-dilation filtering procedure increased the reliability of both parameters of immobility. In case of mice that were poor swimmers, the assessed duration of immobility differed depending on a chosen parameter, thus resulting in the presence or lack of differences between two lines of mice that differed in swimming performance. These results substantiate the need for assessing swimming performance when the duration of immobility in the FST is compared in lines that differ in their swimming "styles". Testing swimming performance can also be important in the

  13. A complex interaction between glycine/NMDA receptors and serotonergic/noradrenergic antidepressants in the forced swim test in mice.

    PubMed

    Poleszak, Ewa; Wlaź, Piotr; Szewczyk, Bernadeta; Wlaź, Aleksandra; Kasperek, Regina; Wróbel, Andrzej; Nowak, Gabriel

    2011-11-01

    Both clinical and preclinical studies demonstrate the antidepressant activity of the functional NMDA receptor antagonists. In this study, we assessed the effects of two glycine/NMDA receptor ligands, namely L-701,324 (antagonist) and D: -cycloserine (a partial agonist) on the action of antidepressant drugs with different pharmacological profiles in the forced swim test in mice. Swim sessions were conducted by placing mice individually in glass cylinders filled with warmed water for 6 min. The duration of behavioral immobility during the last 4 min of the test was evaluated. The locomotor activity of mice was measured with photoresistor actimeters. L-701,324 and D: -cycloserine given with reboxetine (administered in subeffective doses) did not change the behavior of animals in the forced swim test. A potentiating effect was seen when both tested glycine site ligands were given concomitantly with imipramine or fluoxetine in this test. The lesion of noradrenaline nerve terminals produced by DSP-4 neither altered the baseline activity nor influenced the antidepressant-like action of L-701,324 or D: -cycloserine. The depletion of serotonin by p-CPA did not alter baseline activity in the forced swim test. However, it completely antagonized the antidepressant-like action produced by L-701,324 and D: -cycloserine. Moreover, the antidepressant-like effects of imipramine, fluoxetine and reboxetine were abolished by D: -serine, a full agonist of glycine/NMDA receptors. The present study demonstrates that glycine/NMDA receptor functional antagonists enhance the antidepressant-like action of serotonin, but not noradrenaline-based antidepressants and such their activity seems to depend on serotonin rather than noradrenaline pathway.

  14. Additive effects of clonidine and antidepressant drugs in the mouse forced-swimming test.

    PubMed

    Malinge, M; Bourin, M; Colombel, M C; Larousse, C

    1988-01-01

    In the mouse forced-swimming model, dose-dependent reversal of immobility was induced by the alpha-agonist clonidine given IP 30 min before testing. In addition, three preferential inhibitors of 5-HT uptake (citalopram, indalpine and fluvoxamine) had similar activity in the dose range 8-16 mg/kg as did the 5-HT1 agonist 8-OH-DPAT (1-4 mg/kg). Pretreatment with alpha-methyl-paratyrosine (100 mg/kg) did not prevent clonidine (1 mg/kg) action, suggesting that there was mediation by alpha post-junctional receptors. The effect of clonidine was unaltered by prazosin (2 mg/kg) and reversed by yohimbine (4 mg/kg) and 5-MeODMT (1 mg/kg), whereas it was potentiated by reserpine (2.5 mg/kg), methysergide (2 mg/kg) and ketanserin (8 mg/kg). Moreover, an ineffective dose of clonidine (0.06 mg/kg at 45 min pre-testing) made active subthreshold doses of various antidepressants (given at 30 min pre-testing): imipramine (4 mg/kg), amitriptyline (1 mg/kg), maprotiline (8 mg/kg), citalopram (2 mg/kg), indalpine, fluvoxamine and mianserin (4 mg/kg), viloxazine (2 mg/kg). Similar interactions were found with iprindole and nialamide (32 mg/kg), which were inactive alone up to 64 mg/kg, and 8-OH-DPAT (0.5 mg/kg) but not with major and minor tranquillizers. It is suggested that one effect of antidepressants might be the triggering of different relationships between alpha-2 and 5-HT mechanisms.

  15. The forced swim test as a model of depressive-like behavior.

    PubMed

    Yankelevitch-Yahav, Roni; Franko, Motty; Huly, Avrham; Doron, Ravid

    2015-03-02

    The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like behavior in rodents. The FST is based on the assumption that when placing an animal in a container filled with water, it will first make efforts to escape but eventually will exhibit immobility that may be considered to reflect a measure of behavioral despair. This test has been extensively used because it involves the exposure of the animals to stress, which was shown to have a role in the tendency for major depression. Additionally, the FST has been shown to share some of the factors that are influenced or altered by depression in humans, including changes in food consumption, sleep abnormalities and drug-withdrawal-induced anhedonia. The main advantages of this procedure are that it is relatively easy to perform and that its results are easily and quickly analyzed. Moreover, its sensitivity to a broad range of antidepressant drugs that makes it a suitable screening test is one of the most important features leading to its high predictive validity. Despite its appeal, this model has a number of disadvantages. First, the issue of chronic augmentation is problematic in this test because in real life patients need to be treated for at least several weeks before they experience any relief from their symptoms. Last, due to the aversiveness of the FST, it is important to take into account possible influences it might have on brain structure/function if brain analyses are to be carried out following this procedure.

  16. Antidepressant-like effects of psoralen isolated from the seeds of Psoralea corylifolia in the mouse forced swimming test.

    PubMed

    Xu, Qun; Pan, Ying; Yi, Li-Tao; Li, Yu-Cheng; Mo, Shi-Fu; Jiang, Fu-Xin; Qiao, Chun-Feng; Xu, Hong-Xi; Lu, Xiao-Bo; Kong, Ling-Dong; Kung, Hsiang-Fu

    2008-06-01

    The forced swimming test (FST) is suggested to produce abnormalities in the serotonergic and hypothalamic-pituitary-adrenal (HPA) axis systems. Therefore, compounds that attenuate these neurobiological alterations may have potential as antidepressants. The behavioral and biochemical effects of psoralen, a major furocoumarin isolated from Psoralea corylifolia, were investigated in the FST model of depression in male mice. Psoralen significantly reduced immobility and increased swimming without altering climbing in the mouse FST. Psoralen remarkably reversed FST-induced alterations in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in frontal cortex and hippocampus in mice. Furthermore, psoralen attenuated FST-induced elevations in serum corticotropin-releasing factor (CRF) and corticosterone concentrations to normalize the HPA axis activity. These results suggested that psoralen possessed potent antidepressant-like properties which were at least in part mediated by improving the abnormalities in the serotonergic and the HPA axis systems.

  17. Alpha-lipoic acid and N-acetylcysteine protects intensive swimming exercise-mediated germ-cell depletion, pro-oxidant generation, and alteration of steroidogenesis in rat testis.

    PubMed

    Jana, Kuladip; Dutta, Ananya; Chakraborty, Pratip; Manna, Indranil; Firdaus, Syed Benazir; Bandyopadhyay, Debasish; Chattopadhyay, Ratna; Chakravarty, Baidyanath

    2014-09-01

    Prolonged and strenuous exercise has been proposed as a possible source of male-factor infertility. Forced intensive swimming has also been identified as one source of a dysfunctional male reproduction system. The present study evaluated the possible protective role of α-lipoic acid and N-acetylcysteine (NAC) on intensive swimming-induced germ-cell depletion in adult male rats. Forced exhaustive swimming of 1 hr/day, 6 days/week for 8 consecutive weeks resulted in a significant (P < 0.05) reduction in epididymal sperm; testicular androgenic enzyme activities; and plasma and intra-testicular testosterone; and produced different types of germ cells in the seminiferous epithelium cycle. Conversely, plasma corticosterone levels and sperm-head abnormalities increased. Western-blot analysis showed a considerable decrease in testicular StAR protein expression whereas reverse-transcriptase PCR analysis showed no significant change in cytochrome P450scc (Cyp11a1) gene expression. Significant (P < 0.05) elevation in testicular reactive oxygen species (ROS), lipid peroxidation, protein carbonyl content versus reduction in glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione S-transferase, and caspase-3 activities along with a depletion in the glutathione pool, mitochondrial membrane potential (▵ψm ), and intracellular ATP generation. A considerable level of DNA damage in testicular spermatogenic cells were also noted following forced extensive swimming. Alpha-lipoic acid and NAC supplementation prevented the swimming-induced testicular spermatogenic and steroidogenic disorders by lowering ROS generation. We therefore conclude that intensive forced swimming causes germ-cell depletion through the generation of ROS and depletion of steroidogenesis in the testis, which can be protected by the co-administration of α-lipoic acid and NAC. PMID:25104294

  18. Analysis of the swimming activity of Pseudomonas aeruginosa by using photonic force microscope

    NASA Astrophysics Data System (ADS)

    Chan, Chia-Han; Chang, Bo-Jui; Huang, Ying-Jung; Fan, Chia-Chieh; Peng, Hwei-Ling; Chi, Sien; Hsu, Long

    2005-08-01

    Swimming activity of flagella is a main factor of the motility of bacteria. Flagella expressed on the surface of bacterial species serve as a primary means of motility including swimming. We propose to use optical tweezers to analyze the swimming activity of bacteria. The sample bacteria in the work is Pseudomonas aeruginosa, and it is a gram-negative bacterium and often causes leading to burn wound infections, urinary-tract infections, and pneumonia. The single polar flagellum of P. aeruginosa has been demonstrated to be important virulence and colonization factor of this opportunistic pathogen. We demonstrate a gene to regulate the bacterial swimming activity in P. aeruginosa PAO1 by biological method. However, the change of flagellar morphology was not observed by electron microscopy analysis, suggesting that the gene regulates the flagellar rotation that could not be detected by biological method. PFM exhibits a spatial resolution of a few nanometers to detect the relative position of the probe at an acquisition rate over 1 MHz. By binding a probe such as a bead or a quantum dot on the flagella, we expect the rotation of the probe due to the flagella could be detected. It is expected that the study of the swimming activity of P. aeruginosa provide potent method for the pathogenic role of the flagella in P. aeruginosa.

  19. Effect of physical training on metabolic responses of pregnant rats submitted to swimming under thermal stress

    PubMed Central

    Lazo-Osório, Rodrigo Alexis; Pereira, Rafael; Christofani, Junia Scarlatelli; Russo, Adriana Kowalesky; Machado, Marco; Ribeiro, Wellington; da Cruz Piçarro, Ivan

    2009-01-01

    BACKGROUND: The aim of this study is to assess the effect of pre-pregnancy physical training on metabolic responses and its effects on offspring. METHODS: Three groups of rats (n = 7 in each group): sedentary pregnant rats (PS), exercised during pregnancy (PE) and pregnant rats trained before and during pregnancy (PT) were compared. They were separated into three subgroups regarding water temperature: 28°C, 35°C or 39°C. Plasma triglycerides and glucose levels, weight gain during pregnancy and rectal temperature pre and post exercise (swim), as well as the offspring size and weight were analysed. RESULTS: Rectal temperature post exercise was lower than pre exercise at 28°C and 35°C, and higher at 39°C. Weight gain was lower at 39°C for the PT group and at 35°C for the PT and PE groups compared to the PS group. Plasma glucose, at 28°C and 39°C for PS and PE groups, was higher than those obtained at 35°C, while triglycerides were lower. For trained rats, plasma glucose and triglycerides were similar at all water temperatures. Trained rats presented lower triglyceride values at 35°C, and higher triglyceride values at 39°C compared to PS group. Glucose presented inverse results. None of the groups presented fetal reabsorption. However, in the PS group, the offspring presented lower weight gain at 28°C than at 35°C and 39°C. CONCLUSIONS: These results suggest that pre-pregnancy physical training induces steady values of triglycerides and glucose during exercise at all water temperatures. PMID:21772888

  20. Blunted response of pituitary type 1 and brown adipose tissue type 2 deiodinases to swimming training in ovariectomized rats.

    PubMed

    Ignacio, D L; Fortunato, R S; Neto, R A L; da Silva Silvestre, D H; Nigro, M; Frankenfeld, T G P; Werneck-de-Castro, J P S; Carvalho, D P

    2012-10-01

    Ovariectomy leads to significant increase in body weight, but the possible peripheral mechanisms involved in weight gain are still unknown. Since exercise and thyroid hormones modulate energy balance, we aimed to study the effect of swimming training on body weight gain and brown adipose tissue (BAT) type 2 iodothyronine deiodinase responses in ovariectomized (Ox) or sham-operated (Sh) rats. Rats were submitted to a period of 8-week training, 5 days per week with progressive higher duration of exercise protocol. Swimming training program did not totally prevent the higher body mass gain that follows ovariectomy in rats (16.5% decrease in body mass gain in Ox trained rats compared to 22% decrease in sham operated trained animals, in relation to the respective sedentary groups), but training of Ox animals impaired the accumulation of subcutaneous fat pads. Interestingly, swimming training upregulates pituitary type 1 (p<0.001 vs. all groups) and BAT type 2 iodothyronine deiodinases (p<0.05 vs. ShS and OxS) in sham operated but not in Ox rats, indicating an impaired pituitary and peripheral response to exercise in Ox rats. However, BAT mitochondrial O2 consumption significantly increased by swimming training in both sham and Ox groups, indicating that Ox BAT mitochondria responds normally to exercise stimulus, but does not result in a significant reduction of body weight. In conclusion, increased body mass gain produced by Ox is not completely impaired by 8 weeks of high intensity physical training, showing that these animals sustain higher rate of body mass gain independent of being submitted to higher energy expenditure. PMID:22815055

  1. Possible role of dopamine D1-like and D2-like receptors in behavioural activation and evaluation of response efficacy in the forced swimming test.

    PubMed

    D'Aquila, Paolo S; Galistu, Adriana

    2012-03-01

    Based on the different effects of the dopamine D1-like and D2-like receptor antagonists SCH 23390 and raclopride on the measures of licking microstructure in rats ingesting a sucrose solution, we suggested that the behavioural activation of reward-associated responses depends on dopamine D1-like receptor stimulation, and its level is updated, or "reboosted", on the basis of a dopamine D2-like receptor-mediated evaluation process. The aim of this study was to test this hypothesis on the forced swimming test response. The effects of the dopamine D1-like and D2-like receptor antagonists SCH 23390 (0.01-0.04 mg/kg) and raclopride (0.025-0.25 mg/kg) administered before a 15-min exposure to forced swimming, and the response to a second session performed 24 h later, were examined. SCH 23390 dose-dependently reduced climbing scores in the first session and increased them in the second session, but the within-session decline of this measure was similar to that observed in the control group in both sessions. Raclopride-treated subjects showed a slightly reduced level of climbing scores at the beginning of the first session, but persisted in emitting this costly behavioural response up to the end of the session, while no effects were observed in the second session. These results, along with our results examining licking for sucrose, are consistent with the hypothesis that behavioural activation and response effort allocation are directly mediated by dopamine D1-like receptor stimulation, but the level of this activation is updated, or "reboosted", on the basis of a dopamine D2-like receptor-mediated mechanism of response efficacy evaluation.

  2. Effects of repeated treatment with phosphodiesterase-4 inhibitors on cAMP signaling, hippocampal cell proliferation, and behavior in the forced-swim test.

    PubMed

    Xiao, Lan; O'Callaghan, James P; O'Donnell, James M

    2011-08-01

    The effects of repeated treatment with the phosphodiesterase-4 (PDE4) inhibitors rolipram, piclamilast, and 4-(2-(3-(cyclopentyloxy)-4-methoxyphenyl)-2-phenylethyl)pyridine (CDP840), which differ in their interactions with high- and low-affinity binding conformers of the enzyme, were contrasted to those of acute treatment on cAMP signaling, hippocampal cell proliferation, and immobility in the forced-swim test in rats. Repeated treatment with rolipram (1 and 3 mg/kg), piclamilast (0.3 and 1 mg/kg), or CDP840 (10 and 30 mg/kg) for 16 days increased cAMP and phosphorylation of cAMP response element binding protein (pCREB) in hippocampus and prefrontal cortex. In addition, repeated treatment with the PDE4 inhibitors increased proliferation and survival of newborn cells in the hippocampus and produced antidepressant-like effects on behavior, as evidenced by decreased immobility in the forced-swim test. Acute treatment with rolipram (3 mg/kg), piclamilast (1 mg/kg), or CDP840 (30 mg/kg) induced transient increases in cAMP and pCREB in hippocampus and prefrontal cortex, but the dose and time dependence of these effects did not parallel the behavioral effects. Compared with rolipram and piclamilast, repeated treatment with CDP840 exerted lesser effects on neural and behavioral measures, probably because of its weak interaction with the high-affinity binding conformer of PDE4. This suggests the relative importance of the high-affinity binding conformer in the mediation of the long-term effects of PDE4 inhibition on cAMP/pCREB signaling, hippocampal cell proliferation, and antidepressant-like effects on behavior.

  3. Ketamine-enhanced immobility in forced swim test: a possible animal model for the negative symptoms of schizophrenia.

    PubMed

    Chindo, Ben A; Adzu, Bulus; Yahaya, Tijani A; Gamaniel, Karniyus S

    2012-08-01

    Schizophrenia is a chronic and highly complex psychiatric disorder characterised by cognitive dysfunctions, negative and positive symptoms. The major challenge in schizophrenia research is lack of suitable animal models that mimic the core behavioural aspects and symptoms of this devastating psychiatric disorder. In this study, we used classical and atypical antipsychotic drugs to examine the predictive validity of ketamine-enhanced immobility in forced swim test (FST) as a possible animal model for the negative symptoms of schizophrenia. We also evaluated the effects of a selective serotonin reuptake inhibitor (SSRI) on the ketamine-enhanced immobility in FST. Repeated administration of a subanaesthetic dose of ketamine (30 mg kg(-1), i.p., daily for 5 days) enhanced the duration of immobility in FST 24 h after the final injection. The effect, which persisted for at least 21 days after withdrawal of the drug, was neither observed by single treatment with ketamine (30 mg kg(-1) i.p.) nor repeated treatment with amphetamine (1 and 2 mg kg(-1) i.p., daily for 5 days). The enhancing effects of ketamine (30 mg kg(-1) day(-1) i.p.) on the duration of immobility in the FST were attenuated by clozapine (1, 5 and 10 mg kg(-1) i.p.), risperidone (0.25 and 0.5 mg kg(-1) i.p.) and paroxetine (1 and 5 mg kg(-1) i.p.). Haloperidol (0.25 and 0.50 mg kg(-1) day(-1) i.p.) failed to attenuate the ketamine-enhanced immobility in the FST. The repeated ketamine administration neither affects locomotor activity nor motor coordination in rats under the same treatment conditions with the FST, suggesting that the effects of ketamine on the duration of immobility in this study was neither due to motor dysfunction nor peripheral neuromuscular blockade. Our results suggest that repeated treatment with subanaesthetic doses of ketamine enhance the duration of immobility in FST, which might be a useful animal model for the negative symptoms (particularly the depressive features) of

  4. Behavioral, neurochemical and neuroendocrine effects of the ethanolic extract from Curcuma longa L. in the mouse forced swimming test.

    PubMed

    Xia, X; Cheng, G; Pan, Y; Xia, Z H; Kong, L D

    2007-03-21

    Curcuma longa L. (turmeric) has been used for centuries in traditional Chinese medicine as a treatment for mental disorders including depression. The studies described here were undertaken to determine the behavioral, neurochemical and neuroendocrine effects of the ethanolic extract from Curcuma longa using the forced swimming test (FST) in male ICR strain of mice. The ethanolic extract was found to reduce the duration of immobility in the mouse FST when orally administered for 21 days. The extract markedly attenuated swim stress-induced decreases in serotonin, 5-hydroxyindoleacetic acid, noradrenaline and dopamine concentrations, as well as increases in serotonin turnover. Furthermore, the ethanolic extract of Curcuma longa significantly reversed the swim stress-induced increases in serum corticotropin-releasing factor and cortisol levels. Under these conditions, the ethanolic extract of Curcuma longa was partly different from fluoxetine and amitriptyline. These results suggested that antidepressant properties of the ethanolic extract of Curcuma longa was mediated through regulations of neurochemical and neuroendocrine systems and it may be a useful agent against depression.

  5. Dual monoamine modulation for the antidepressant-like effect of lamotrigine in the modified forced swimming test.

    PubMed

    Consoni, Fernando T; Vital, Maria A B F; Andreatini, Roberto

    2006-08-01

    Lamotrigine is an anticonvulsant drug that exhibits a clinical antidepressant effect. However, few studies have been conducted with lamotrigine in animal models of depression and its mechanism of antidepressant action is still unclear. The present study evaluates the effect of lamotrigine (5-20mg/kg, i.p.) in the modified forced swimming test and compare its behavior pattern in the test with those of paroxetine (20mg/kg, i.p.), nortriptyline (20mg/kg, i.p.) and dizolcipine-MK-801 (0.1mg/kg, i.p.). The effect of lamotrigine on locomotor activity and memory was also studied in order to exclude false-positive results. At low doses, lamotrigine (10mg/kg) decreased immobility and increased climbing scores, a similar pattern to nortriptyline. A higher lamotrigine dose (20mg/kg) also increased swimming scores. Lamotrigine neither changed locomotion in the open-field test nor impaired habituation. Paroxetine and dizolcipine decreased immobility and increased swimming. Dizolcipine also decreased climbing. However, although the effects of paroxetine and nortriptyline were seen without effect on locomotor activity, dizolcipine increased locomotor activity. The present study indicates that the antidepressant-like effect of lamotrigine is probably related to noradrenergic/serotonergic systems.

  6. Antidepressant-like effects of ketamine, norketamine and dehydronorketamine in forced swim test: Role of activity at NMDA receptor.

    PubMed

    Sałat, Kinga; Siwek, Agata; Starowicz, Gabriela; Librowski, Tadeusz; Nowak, Gabriel; Drabik, Urszula; Gajdosz, Ryszard; Popik, Piotr

    2015-12-01

    Ketamine produces rapid and long-lasting antidepressant effects in patients. The involvement of ketamine metabolites in these actions has been proposed. The effects of ketamine and its metabolites norketamine and dehydronorketamine on ligand binding to 80 receptors, ion channels and transporters was investigated at a single concentration of 10 μM. The affinities of all three compounds were then assessed at NMDA receptors using [3H]MK-801 binding. The dose-response relationships of all 3 compounds in the forced swim test were also investigated in mice 30 min after IP administration. The effects of ketamine and norketamine (both 50 mg/kg) were then examined at 30 min, 3 days and 7 days post administration. Among the 80 potential targets examined, only NMDA receptors were affected with a magnitude of >50% by ketamine and norketamine at the concentration of 10 μM. The Ki values of ketamine, norketamine and dehydronorketamine at NMDA receptors were 0.119±0.01, 0.97±0.1 and 3.21±0.3 μM, respectively. Ketamine and norketamine reduced immobility with minimum effective doses (MEDs) of 10 and 50 mg/kg, respectively; dehydronorketamine did not affect immobility at doses of up to 50 mg/kg. Neither ketamine nor norketamine reduced immobility in the forced swim test 3 and 7 days following administration. Further, oral administration of ketamine (5-50 mg/kg) did not affect immobility. We demonstrate that ketamine and norketamine but not dehydronorketamine given acutely at subanesthetic doses reduced immobility in the forced swim test. These antidepressant-like effects appear attributable to NMDA receptor inhibition.

  7. The antidepressant effects of curcumin in the forced swimming test involve 5-HT1 and 5-HT2 receptors.

    PubMed

    Wang, Rui; Xu, Ying; Wu, Hong-Li; Li, Ying-Bo; Li, Yu-Hua; Guo, Jia-Bin; Li, Xue-Jun

    2008-01-01

    Curcuma longa is a main constituent of many traditional Chinese medicines, such as Xiaoyao-san, used to manage mental disorders effectively. Curcumin is a major active component of C. longa and its antidepressant-like effect has been previously demonstrated in the forced swimming test. The purpose of this study was to explore the possible contribution of serotonin (5-HT) receptors in the behavioral effects induced by curcumin in this animal model of depression. 5-HT was depleted by the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA, 100 mg/kg, i.p.) prior to the administration of curcumin, and the consequent results showed that PCPA blocked the anti-immobility effect of curcumin in forced swimming test, suggesting the involvement of the serotonergic system. Moreover, pre-treatment of pindolol (10 mg/kg, i.p., a beta-adrenoceptors blocker/5-HT(1A/1B) receptor antagonist), 4-(2'-methoxy-phenyl)-1-[2'-(n-2''-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (p-MPPI, 1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), or 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol (isamoltane, 2.5 mg/kg, i.p., a 5-HT(1B) receptor antagonist) was found to prevent the effect of curcumin (10 mg/kg) in forced swimming test. On the other hand, a sub-effective dose of curcumin (2.5 mg/kg, p.o.) produced a synergistic effect when given jointly with (+)-8-hydroxy-2-(di-n-propylamino)tetralin, (8-OH-DPAT, 1 mg/kg, i.p., a 5-HT(1A) receptor agonist), anpirtoline (0.25 mg/kg, i.p., a 5-HT(1B) receptor agonist) or ritanserin (4 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), but not with ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist with higher affinity to 5-HT(2A) receptor) or R(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1 mg/kg, i.p., a 5-HT(2A) receptor agonist). Taken together, these results indicate that the antidepressant-like effect of curcumin in the forced swimming test is related to serotonergic system and may be mediated by, at least

  8. Dose-dependent influence of buspirone on the activities of selective serotonin reuptake inhibitors in the mouse forced swimming test.

    PubMed

    Redrobe, J P; Bourin, M

    1998-07-01

    Recent clinical data suggest that buspirone may enhance the efficacy and/or reduce the latency to therapeutic effect of selective serotonin reuptake inhibitors (SSRIs) in unipolar major depressive disorder. The present study, using the mouse forced swimming test, was performed to investigate further the mechanisms involved in the potential antidepressant-enhancing effects of buspirone. Prior administration of buspirone (0.06 mg kg(-1), i.p.) significantly enhanced the anti-immobility effects of subactive doses of fluvoxamine (4 mg kg(-1), i.p.; P < 0.01), paroxetine (4 mg kg(-1), i.p.; P < 0.01), citalopram (4 mg kg(-1), i.p.; P < 0.01) and sertraline (2 mg kg(-1), i.p.; P < 0.01) in the forced swimming test. However, pretreatment with buspirone did not induce antidepressant-like effects when tested in combination with fluoxetine (4 mg kg(-1), i.p.). Each antidepressant tested reduced immobility time in the forced swimming test [citalopram (16 mg kg(-1), i.p.; P < 0.01), fluoxetine (32 mg kg(-1), i.p.; P < 0.01), fluvoxamine (32 mg kg(-1), i.p.; P < 0.01), paroxetine (16 mg kg(-1), i.p.; P < 0.01) and sertraline (16 mg kg(-1), i.p.; P < 0.01)]. Pretreatment with buspirone (0.5 mg kg(-1), i.p.), or its major metabolite 1-PP (0.5 mg kg(-1), i.p.), attenuated all SSRI-induced anti-immobility effects (P < 0.01). Concomitant studies of locomotor activity ruled out any stimulant or sedative effects of the interactions. The results of the present study suggested that low dose buspirone enhanced the activity of subactive doses of SSRIs in the mouse forced swimming test, probably via an action at 5-HT1A receptors. On the other hand, a high dose of buspirone attenuated the antidepressant-like effects of active doses of these drugs, possibly via the generation of an active metabolite (1-PP) acting at alpha2-adrenoreceptors.

  9. Increased depressive behaviour in females and heightened corticosterone release in males to swim stress after adolescent social stress in rats.

    PubMed

    Mathews, Iva Z; Wilton, Aleena; Styles, Amy; McCormick, Cheryl M

    2008-06-26

    We previously reported that males undergoing chronic social stress (SS) (daily 1h isolation and new cage partner on days 30-45 of age) in adolescence habituated (decreased corticosterone release) to the homotypic stressor, but females did not. Here, we report that adolescent males exposed to chronic social stress had potentiated corticosterone release to a heterotypic stressor (15 min of swim stress) compared to acutely stressed and control males. The three groups of males did not differ in depressive-like behaviour (time spent immobile) during the swim stress. Corticosterone release in socially stressed females was elevated 45 min after the swim stress compared to acutely stressed and control females, and socially stressed females exhibited more depressive behaviour (longer durations of immobility and shorter durations of climbing) than the other females during the swim stress. Separate groups of rats were tested as adults several weeks after the social stress, and there were no group differences in corticosterone release after the swim stress. The only group difference in behaviour among the adults was more time spent climbing in socially stressed males than in controls. Thus, there are sex-specific effects of social stress in adolescence on endocrine responses and depressive behaviour to a heterotypic stressor, but, unlike for anxiety, substantial recovery is evident in adulthood in the absence of intervening stress exposures.

  10. Injections of the NMDA-antagonist D-2-amino-7-phosphonoheptanoic acid (AP-7) into the nucleus accumbens of rats enhance switching between cue-directed behaviours in a swimming test procedure.

    PubMed

    van den Bos, R; Charria Ortiz, G A; Cools, A R

    1992-06-01

    The present study explores the behavioural effects of intra-accumbens injections of D-2-amino-7-phosphonoheptanoic acid (AP-7), a selective competitive N-methyl-D-aspartate (NMDA) receptor antagonist, using a swimming test procedure, in which rats were forced to swim for 6 min. The behaviour of the rats was analysed in terms of cue-directed (CDBs) and non-cue-directed behaviours (NCDBs). AP-7 (100-500 ng/0.5 microliter) dose-dependently enhanced the number of switches to CDBs, without affecting the number of switches to NCDBs. Further analysis of the data showed that the number of switches between CDBs was enhanced, while no effect was found on the number of switches from NCDBs to CDBs, from CDBs to NCDBs or between NCDBs. These data suggest that the NMDA-receptor in the nucleus accumbens is involved in the ability to switch between cue-directed behaviours.

  11. Boxfish swimming paradox resolved: forces by the flow of water around the body promote manoeuvrability.

    PubMed

    Van Wassenbergh, S; van Manen, K; Marcroft, T A; Alfaro, M E; Stamhuis, E J

    2015-02-01

    The shape of the carapace protecting the body of boxfishes has been attributed an important hydrodynamic role in drag reduction and in providing automatic, flow-direction realignment and is therefore used in bioinspired design of cars. However, tight swimming-course stabilization is paradoxical given the frequent, high-performance manoeuvring that boxfishes display in their spatially complex, coral reef territories. Here, by performing flow-tank measurements of hydrodynamic drag and yaw moments together with computational fluid dynamics simulations, we reverse several assumptions about the hydrodynamic role of the boxfish carapace. Firstly, despite serving as a model system in aerodynamic design, drag-reduction performance was relatively low compared with more generalized fish morphologies. Secondly, the current theory of course stabilization owing to flow over the boxfish carapace was rejected, as destabilizing moments were found consistently. This solves the boxfish swimming paradox: destabilizing moments enhance manoeuvrability, which is in accordance with the ecological demands for efficient turning and tilting.

  12. Boxfish swimming paradox resolved: forces by the flow of water around the body promote manoeuvrability

    PubMed Central

    Van Wassenbergh, S.; van Manen, K.; Marcroft, T. A.; Alfaro, M. E.; Stamhuis, E. J.

    2015-01-01

    The shape of the carapace protecting the body of boxfishes has been attributed an important hydrodynamic role in drag reduction and in providing automatic, flow-direction realignment and is therefore used in bioinspired design of cars. However, tight swimming-course stabilization is paradoxical given the frequent, high-performance manoeuvring that boxfishes display in their spatially complex, coral reef territories. Here, by performing flow-tank measurements of hydrodynamic drag and yaw moments together with computational fluid dynamics simulations, we reverse several assumptions about the hydrodynamic role of the boxfish carapace. Firstly, despite serving as a model system in aerodynamic design, drag-reduction performance was relatively low compared with more generalized fish morphologies. Secondly, the current theory of course stabilization owing to flow over the boxfish carapace was rejected, as destabilizing moments were found consistently. This solves the boxfish swimming paradox: destabilizing moments enhance manoeuvrability, which is in accordance with the ecological demands for efficient turning and tilting. PMID:25505133

  13. Forces and shapes as determinants of micro-swimming: effect on synchronisation and the utilisation of drag.

    PubMed

    Pande, Jayant; Smith, Ana-Sunčana

    2015-03-28

    In this analytical study we demonstrate the richness of behaviour exhibited by bead-spring micro-swimmers, both in terms of known yet not fully explained effects such as synchronisation, and hitherto undiscovered phenomena such as the existence of two transport regimes where the swimmer shape has fundamentally different effects on the velocity. For this purpose we employ a micro-swimmer model composed of three arbitrarily-shaped rigid beads connected linearly by two springs. By analysing this swimmer in terms of the forces on the different beads, we determine the optimal kinematic parameters for sinusoidal driving, and also explain the pusher/puller nature of the swimmer. Moreover, we show that the phase difference between the swimmer's arms automatically attains values which maximise the swimming speed for a large region of the parameter space. Apart from this, we determine precisely the optimal bead shapes that maximise the velocity when the beads are constrained to be ellipsoids of a constant volume or surface area. On doing so, we discover the surprising existence of the aforementioned transport regimes in micro-swimming, where the motion is dominated by either a reduction of the drag force opposing the beads, or by the hydrodynamic interaction amongst them. Under some conditions, these regimes lead to counter-intuitive effects such as the most streamlined shapes forming locally the slowest swimmers.

  14. Comparative evaluation of forced swim test and tail suspension test as models of negative symptom of schizophrenia in rodents.

    PubMed

    Chatterjee, Manavi; Jaiswal, Manoj; Palit, Gautam

    2012-01-01

    Previous studies have shown that the administration of NMDA antagonist can induce negative symptoms of schizophrenia which can be tested through the enhanced immobility observed in the forced swim test (FST). In the present study, we have compared the effects of acute as well as chronic administration of a noncompetitive NMDA receptor antagonist, ketamine on FST, and another behaviour despair model, tail suspension test (TST). Our observations suggest that chronic ketamine administration induced a state of enhanced immobility in FST, but such findings were not replicated in the TST model. Further, in FST, treatment with clozapine reverses the ketamine-induced immobility in mice, whereas it enhances the immobility duration in the TST model. However, haloperidol showed no protective effects in both models. The data suggests that although both of these tests show common behavioural measure of feeling despair, however, the underlying pathophysiology seems to be different. Hence, forced swim test but not tail suspension test can be used as a model of negative symptom of psychosis in mice.

  15. Chronic aerobic swimming exercise promotes functional and morphological changes in rat ileum.

    PubMed

    Araujo, Layanne Cabral da Cunha; de Souza, Iara Leão Luna; Vasconcelos, Luiz Henrique César; Brito, Aline de Freitas; Queiroga, Fernando Ramos; Silva, Alexandre Sérgio; da Silva, Patrícia Mirella; Cavalcante, Fabiana de Andrade; da Silva, Bagnólia Araújo

    2015-01-01

    Several studies have reported the gastrointestinal (GI) effects promoted by the physical exercise. Thus, we aimed to evaluate the influence of swimming exercise on the contractile reactivity, lipid peroxidation and morphology of rat ileum. Wistar rats were divided into sedentary (SED) and groups exercised for two (EX2), four (EX4), six (EX6) or eight (EX8) weeks, 5 days/week. Animals were killed; the ileum was removed and suspended in organ baths where the isotonic contractions were recorded. Lipid peroxidation was evaluated by MDA (malondialdehyde) measurement with TBARS (thiobarbituric acid reactive substances) assay and morphology by histological staining. Cumulative concentration-response curves to KCl were attenuated, as the Emax values were changed from 100% (SED) to 63.1±3.9 (EX2), 48.8±3.8 (EX4), 19.4±1.8 (EX6) and 59.4±2.8% (EX8). Similarly, cumulative concentration-response curves to carbamylcholine hydrochloride (CCh) were attenuated, as the Emax values were changed from 100% (SED) to 74.1±5.4 (EX2), 75.9±5.2 (EX4) and 62.9±4.6 (EX6), but not in the EX8 (89.7±3.4%). However, CCh potency was increased in this latter, as the EC50 was altered from 1.0±0.1×10(-6) (SED) to 2.1±0.4×10(-7) (EX8). MDA concentration was altered only in EX4 (44.3±4.4) compared with SED (20.6±3.6 μmol/l). Circular layer was reduced in SED when compared with the exercised groups. Conversely, longitudinal layer was increased. In conclusion, chronic swimming exercise reduces the ileum contraction, equilibrates the oxidative damage and promotes changes in tissue size to establish an adaptation to the exercise. PMID:26424698

  16. Chronic aerobic swimming exercise promotes functional and morphological changes in rat ileum

    PubMed Central

    da Cunha Araujo, Layanne Cabral; de Souza, Iara Leão Luna; Vasconcelos, Luiz Henrique César; de Freitas Brito, Aline; Queiroga, Fernando Ramos; Silva, Alexandre Sérgio; da Silva, Patrícia Mirella; de Andrade Cavalcante, Fabiana; da Silva, Bagnólia Araújo

    2015-01-01

    Several studies have reported the gastrointestinal (GI) effects promoted by the physical exercise. Thus, we aimed to evaluate the influence of swimming exercise on the contractile reactivity, lipid peroxidation and morphology of rat ileum. Wistar rats were divided into sedentary (SED) and groups exercised for two (EX2), four (EX4), six (EX6) or eight (EX8) weeks, 5 days/week. Animals were killed; the ileum was removed and suspended in organ baths where the isotonic contractions were recorded. Lipid peroxidation was evaluated by MDA (malondialdehyde) measurement with TBARS (thiobarbituric acid reactive substances) assay and morphology by histological staining. Cumulative concentration-response curves to KCl were attenuated, as the Emax values were changed from 100% (SED) to 63.1±3.9 (EX2), 48.8±3.8 (EX4), 19.4±1.8 (EX6) and 59.4±2.8% (EX8). Similarly, cumulative concentration-response curves to carbamylcholine hydrochloride (CCh) were attenuated, as the Emax values were changed from 100% (SED) to 74.1±5.4 (EX2), 75.9±5.2 (EX4) and 62.9±4.6 (EX6), but not in the EX8 (89.7±3.4%). However, CCh potency was increased in this latter, as the EC50 was altered from 1.0±0.1×10−6 (SED) to 2.1±0.4×10−7 (EX8). MDA concentration was altered only in EX4 (44.3±4.4) compared with SED (20.6±3.6 μmol/l). Circular layer was reduced in SED when compared with the exercised groups. Conversely, longitudinal layer was increased. In conclusion, chronic swimming exercise reduces the ileum contraction, equilibrates the oxidative damage and promotes changes in tissue size to establish an adaptation to the exercise. PMID:26424698

  17. Desipramine and citalopram attenuate pretest swim-induced increases in prodynorphin immunoreactivity in the dorsal bed nucleus of the stria terminalis and the lateral division of the central nucleus of the amygdala in the forced swimming test.

    PubMed

    Chung, Sung; Kim, Hee Jeong; Kim, Hyun Ju; Choi, Sun Hye; Cho, Jin Hee; Cho, Yun Ha; Kim, Dong-Hoon; Shin, Kyung Ho

    2014-10-01

    Dynorphin in the nucleus accumbens shell plays an important role in antidepressant-like effect in the forced swimming test (FST), but it is unclear whether desipramine and citalopram treatments alter prodynorphin levels in other brain areas. To explore this possibility, we injected mice with desipramine and citalopram 0.5, 19, and 23 h after a 15-min pretest swim and observed changes in prodynorphin expression before the test swim, which was conducted 24 h after the pretest swim. The pretest swim increased prodynorphin immunoreactivity in the dorsal bed nucleus of the stria terminalis (dBNST) and lateral division of the central nucleus of the amygdala (CeL). This increase in prodynorphin immunoreactivity in the dBNST and CeL was blocked by desipramine and citalopram treatments. Similar changes in prodynorphin mRNA levels were observed in the dBNST and CeL, but these changes did not reach significance. To understand the underlying mechanism, we assessed changes in phosphorylated CREB at Ser(133) (pCREB) immunoreactivity in the dBNST and central nucleus of the amygdala (CeA). Treatment with citalopram but not desipramine after the pretest swim significantly increased pCREB immunoreactivity only in the dBNST. These results suggest that regulation of prodynorphin in the dBNST and CeL before the test swim may be involved in the antidepressant-like effect of desipramine and citalopram in the FST and suggest that changes in pCREB immunoreactivity in these areas may not play an important role in the regulation of prodynorphin in the dBNST and CeA.

  18. Swimming exercise and diphenyl diselenide-supplemented diet affect the serum levels of pro- and anti-inflammatory cytokines differently depending on the age of rats.

    PubMed

    Leite, Marlon R; Cechella, José L; Mantovani, Anderson C; Duarte, Marta M M F; Nogueira, Cristina W; Zeni, Gilson

    2015-01-01

    The increase in the inflammatory process is one of the main factors that contribute to aging. The aim of this study was to investigate the effects of a diphenyl diselenide (PhSe)2-supplemented diet (1p.p.m., 4weeks) and swimming exercise (3% of body weight, 20min per day, 4weeks) on the serum levels of cytokines in Wistar rats of different ages. The results demonstrated an increase in the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNFα and INFγ) and a decrease in the levels of IL-10, an anti-inflammatory cytokine, with age. In middle-age rats, the swimming exercise and (PhSe)2-supplemented diet decreased serum levels of pro-inflammatory cytokines and increased the levels of IL-10. By contrast, in old rats the swimming exercise protocol increased the serum levels of pro-inflammatory cytokines and decreased the levels IL-10. Diet supplemented with (PhSe)2 did not alter the serum levels of cytokines in old rats. Middle-age and old rats subjected to swimming exercise and supplemented with (PhSe)2 in the diet had a decrease in the serum levels of pro-inflammatory cytokines and an increase in the levels of IL-10. This study demonstrated that swimming exercise and (PhSe)2-supplemented diet affect the serum levels of pro- and anti-inflammatory cytokines differently depending on the age of rats. (PhSe)2 supplemented in the diet had an anti-inflammatory effect, similar to that of induced by swimming exercise, in middle-age rats and reversed the pro-inflammatory effects of swimming exercise in old rats.

  19. Antidepressant-like effects of echo-planar magnetic resonance imaging in mice determined using the forced swimming test.

    PubMed

    Aksoz, Elif; Aksoz, Tolga; Bilge, S Sirri; Ilkaya, Fatih; Celik, Suleyman; Diren, H Baris

    2008-10-21

    Echo-planar magnetic resonance imaging (EP-MRI), which is novel variant of MRI, is thought to have antidepressant properties in humans and animal models. Using the forced swimming test (FST), we investigated which monoaminergic system in mice is affected by EP-MRI. The short- and long-term effects of EP-MRI on immobility time in the FST and motor activity within a locomotor activity cage were examined. Two groups of mice underwent 20 min of EP-MRI in an MR scanner (Siemens, 1.5 T Symphony) either 23.5 or 1 h before the start of the second session of the FST. In both groups, the immobility duration in the FST was reduced, similar to effective antidepressant drug treatments. Climbing behavior in the 1-h group and swimming behavior in the 23.5-h group increased significantly, similar to that seen after the administration of desipramine (a noradrenaline reuptake inhibitor) and sertraline (a selective serotonin reuptake inhibitor), respectively. The findings support the hypothesis that EP-MRI has an antidepressant-like effect. We suggest that the antidepressant-like effect begins in the early period with noradrenaline systems and is maintained in the late period with serotonin systems.

  20. [Mechanism of action of clonidine in the forced-swimming test in mice].

    PubMed

    Malinge, M; Colombel, M C; Bourin, M

    1989-01-01

    Clonidine displays immobility-reducing effects in the mouse swimming model at doses (0.06-16 mg/kg IP) which decrease spontaneous motility. Tricyclic antidepressants evoke a similar dissociation in motor activity. The immobility-reducing effect of clonidine (1 mg/kg at 30 min pretesting) was reversed by yohimbine (4 mg/kg) but was unaffected by prazosin (2 mg/kg) or alpha-methyl-paratyrosine (100 mg/kg), and was enhanced by reserpine (2.5 mg/kg). Mediation by alpha-2 postjunctional receptors was thus suggested. However, two 5-HT receptor blockers--methysergide (2 mg/kg) and ketanserin (8 mg/kg)--increased this effect of clonidine whereas the non selective agonist 5-MeODMT (1 mg/kg) reduced clonidine action. Conversely, pretreatment with a subthreshold dose of clonidine (0.06 mg/kg at 45 min pretesting) made effective subthreshold doses of three 5-HT uptake inhibitors (citalopram 2 mg/kg, indalpine and fluvoxamine 4 mg/kg) and of the 5-HT1 receptor agonist 8-OH-DPAT (0.5 mg/kg). According to these data, the mouse swimming model would trigger functional relationships between central alpha-noradrenergic and serotonergic mechanisms.

  1. N-palmitoylethanolamide, an endocannabinoid, exhibits antidepressant effects in the forced swim test and the tail suspension test in mice.

    PubMed

    Yu, Hai-Ling; Deng, Xian-Qing; Li, Ying-Jun; Li, Ying-Chun; Quan, Zhe-Shan; Sun, Xian-Yu

    2011-01-01

    The antidepressant-like effects of N-palmitoylethanolamide (PEA), a putative endocannabinoid, was investigated in mice using the tail suspension test (TST) and the forced swimming test (FST). In TST, PEA (10, 20, and 40 mg/kg) produced a statistically significant reduction in immobility (50, 32, and 34%, respectively, vs. the control group), whereas fluoxetine (20 mg/kg) reduced immobility by 38%. In FST, PEA (5, 10, and 20 mg/kg) produced a statistically significant reduction in immobility (15, 21, and 36%, respectively), whereas fluoxetine (20 mg/kg) reduced immobility by 18%. Moreover, PEA (20 mg/kg) did not significantly change motor activity in a spontaneous behavioral test. In conclusion, PEA (dose range of 5-40 mg/kg) administered orally reduced immobility in TST and FST, comparable to the antidepressant effect of fluoxetine, and had no effect on spontaneous activity in mice. PMID:21857095

  2. Identification of multiple genetic loci in the mouse controlling immobility time in the tail suspension and forced swimming tests.

    PubMed

    Abou-Elnaga, Ahmed F; Torigoe, Daisuke; Fouda, Mohamed M; Darwish, Ragab A; Abou-Ismail, Usama A; Morimatsu, Masami; Agui, Takashi

    2015-05-01

    Depression is one of the most famous psychiatric disorders in humans in all over the countries and considered a complex neurobehavioral trait and difficult to identify causal genes. Tail suspension test (TST) and forced swimming test (FST) are widely used for assessing depression-like behavior and antidepressant activity in mice. A variety of antidepressant agents are known to reduce immobility time in both TST and FST. To identify genetic determinants of immobility duration in both tests, we analyzed 101 F2 mice from an intercross between C57BL/6 and DBA/2 strains. Quantitative trait locus (QTL) mapping using 106 microsatellite markers revealed three loci (two significant and one suggestive) and five suggestive loci controlling immobility time in the TST and FST, respectively. Results of QTL analysis suggest a broad description of the genetic architecture underlying depression, providing underpinnings for identifying novel molecular targets for antidepressants to clear the complex genetic mechanisms of depressive disorders.

  3. Swimming Training Modulates Nitric Oxide-Glutamate Interaction in the Rostral Ventrolateral Medulla in Normotensive Conscious Rats.

    PubMed

    Raquel, Hiviny de A; Masson, Gustavo S; Barna, Barbara Falquetto; Zanluqui, Nágela G; Pinge-Filho, Phileno; Michelini, Lisete C; Martins-Pinge, Marli C

    2016-01-01

    We evaluated the effects of swimming training on nitric oxide (NO) modulation to glutamate microinjection within the rostral ventrolateral medulla (RVLM) in conscious freely moving rats. Male Wistar rats were submitted to exercise training (Tr) by swimming or kept sedentary (Sed) for 4 weeks. After the last training session, RVLM guide cannulas and arterial/venous catheters were chronically implanted. Arterial pressure (AP), heart rate (HR), and baroreflex control of HR (loading/unloading of baroreceptors) were recorded in conscious rats at rest. Pressor response to L-glutamate in the RVLM was compared before and after blockade of local nitric oxide (NO) production. In other Tr and Sed groups, brain was harvested for gene (qRT-PCR) and protein (immunohistochemistry) expression of NO synthase (NOS) isoforms and measurement of NO content (nitrite assay) within the RVLM. Trained rats exhibited resting bradycardia (average reduction of 9%), increased baroreflex gain (Tr: -4.41 ± 0.5 vs. Sed: -2.42 ± 0.31 b/min/mmHg), and unchanged resting MAP. The pressor response to glutamate was smaller in the Tr group (32 ± 4 vs. 53 ± 2 mmHg, p < 0.05); this difference disappeared after RVLM pretreatment with carboxy-PTIO (NO scavenger), Nw-Propyl-L-Arginine and L-NAME (NOS inhibitors). eNOS immunoreactivity observed mainly in RVLM capillaries was higher in Tr, but eNOS gene expression was reduced. nNOS gene and protein expression was slightly reduced (-29 and -9%, respectively, P > 0.05). Also, RVLM NO levels were significantly reduced in Tr (-63% vs. Sed). After microinjection of a NO-donor, the attenuated pressor response of L-glutamate in Tr group was restored. Data indicate that swimming training by decreasing RVLM NO availability and glutamatergic neurotransmission to locally administered glutamate may contribute to decreased sympathetic activity in trained subjects. PMID:27378935

  4. Swimming Training Modulates Nitric Oxide-Glutamate Interaction in the Rostral Ventrolateral Medulla in Normotensive Conscious Rats

    PubMed Central

    Raquel, Hiviny de A.; Masson, Gustavo S.; Barna, Barbara Falquetto; Zanluqui, Nágela G.; Pinge-Filho, Phileno; Michelini, Lisete C.; Martins-Pinge, Marli C.

    2016-01-01

    We evaluated the effects of swimming training on nitric oxide (NO) modulation to glutamate microinjection within the rostral ventrolateral medulla (RVLM) in conscious freely moving rats. Male Wistar rats were submitted to exercise training (Tr) by swimming or kept sedentary (Sed) for 4 weeks. After the last training session, RVLM guide cannulas and arterial/venous catheters were chronically implanted. Arterial pressure (AP), heart rate (HR), and baroreflex control of HR (loading/unloading of baroreceptors) were recorded in conscious rats at rest. Pressor response to L-glutamate in the RVLM was compared before and after blockade of local nitric oxide (NO) production. In other Tr and Sed groups, brain was harvested for gene (qRT-PCR) and protein (immunohistochemistry) expression of NO synthase (NOS) isoforms and measurement of NO content (nitrite assay) within the RVLM. Trained rats exhibited resting bradycardia (average reduction of 9%), increased baroreflex gain (Tr: −4.41 ± 0.5 vs. Sed: −2.42 ± 0.31 b/min/mmHg), and unchanged resting MAP. The pressor response to glutamate was smaller in the Tr group (32 ± 4 vs. 53 ± 2 mmHg, p < 0.05); this difference disappeared after RVLM pretreatment with carboxy-PTIO (NO scavenger), Nw-Propyl-L-Arginine and L-NAME (NOS inhibitors). eNOS immunoreactivity observed mainly in RVLM capillaries was higher in Tr, but eNOS gene expression was reduced. nNOS gene and protein expression was slightly reduced (−29 and −9%, respectively, P > 0.05). Also, RVLM NO levels were significantly reduced in Tr (−63% vs. Sed). After microinjection of a NO-donor, the attenuated pressor response of L-glutamate in Tr group was restored. Data indicate that swimming training by decreasing RVLM NO availability and glutamatergic neurotransmission to locally administered glutamate may contribute to decreased sympathetic activity in trained subjects. PMID:27378935

  5. Repeated cold water swim produces delayed nociceptive responses, but not analgesia, for tonic pain in the rat.

    PubMed

    Fuchs, P N; Melzack, R

    1997-05-01

    Earlier studies have demonstrated that cold water swim (CWS) produces stress-induced analgesia in tests of brief, phasic pain and produces a delayed nociceptive response (DNR) for more prolonged tonic pain. The present study reports the effect of repeated CWS on tonic pain, as measured by the formalin test. One group of rats was exposed to a 3.5-min swim in 2 degrees C water immediately prior to the formalin injection, to a 1.5-min swim at 50 min, and to another 1.5-min swim at 100 min postformalin injection. Compared to the no-swim control group, subjects which received repeated CWS had dramatically altered formalin pain responses. Formalin responses began just over 3 h postformalin injection, peaked at 4 h, and were still present at 5 h. Inspection of individual responses revealed a substantial degree of variability in the onset of responses, although the magnitude and duration of the formalin pain response remained at the same levels as those of control subjects. The lack of a decrease in the magnitude and duration of the delayed formalin responses indicates that repeated CWS does not produce analgesia for tonic pain. The period of stress, therefore, produces pain suppression but not loss of the mechanisms that subsequently underlie the pain. Earlier controls have ruled out peripheral mechanisms (such as retention of the formalin in the paw tissue). Rather, a memory mechanism appears to have been indicated and it is not lost, but persists until it can be manifested. Further research is needed to study the mechanisms responsible for the DNR.

  6. The hydrophobic dipeptide Leu-Ile inhibits immobility induced by repeated forced swimming via the induction of BDNF.

    PubMed

    Furukawa-Hibi, Yoko; Nitta, Atsumi; Ikeda, Takeshi; Morishita, Koji; Liu, Wenting; Ibi, Daisuke; Alkam, Tursun; Nabeshima, Toshitaka; Yamada, Kiyofumi

    2011-07-01

    Depression has recently become a serious problem in society worldwide. However, we lack appropriate therapeutic tools, since the causes of depression remain unclear. Degeneration of neuronal cells and a decrease in neurogenesis have been suggested recently as two of the factors responsible for depression-like behavior. Furthermore, brain-derived neurotrophic factor (BDNF) is also suggested to be an important factor in recovering from such behavior. We have previously demonstrated that the hydrophobic dipeptide leucyl-isoleucine (Leu-Ile) induces BDNF in cultured neuronal cells. We therefore investigated possible antidepressant-like effects of Leu-Ile in an animal model using the repeated forced swim test (FST). Mice were forced to swim for 6 min once a day in a cylinder containing water. The mice were treated with Leu-Ile s.c. or p.o. immediately after each FST. Five-day repeated Leu-Ile treatment significantly increased BDNF mRNA levels and activated the BDNF/Akt/mTOR signaling pathway in the hippocampi of the mice. While 2-week repeated FST increased immobility time, Leu-Ile treatment for 2 weeks offset this increase. In C57BL/6J-BDNF heterozygous knockout (BDNF(+/-)) mice, Leu-Ile failed to reduce the immobility time increased by repeated FST. We next investigated the extent of cell proliferation in the hippocampus as 5-bromo-2'-deoxy-uridine (BrdU) uptake into hippocampal cells. Repeated FST significantly reduced the number of BrdU-positive cells in the hippocampal dentate gyrus, while this deficit was prevented by repeated Leu-Ile treatment. These results suggest that Leu-Ile has an antidepressant-like effect, at least in part by supporting cell proliferation through the BDNF signaling pathway.

  7. Effect of desipramine and citalopram treatment on forced swimming test-induced changes in cocaine- and amphetamine-regulated transcript (CART) immunoreactivity in mice.

    PubMed

    Chung, Sung; Kim, Hee Jeong; Kim, Hyun Ju; Choi, Sun Hye; Kim, Jin Wook; Kim, Jeong Min; Shin, Kyung Ho

    2014-05-01

    Recent study demonstrates antidepressant-like effect of cocaine- and amphetamine-regulated transcript (CART) in the forced swimming test (FST), but less is known about whether antidepressant treatments alter levels of CART immunoreactivity (CART-IR) in the FST. To explore this possibility, we assessed the treatment effects of desipramine and citalopram, which inhibit the reuptake of norepinephrine and serotonin into the presynaptic terminals, respectively, on changes in levels of CART-IR before and after the test swim in mouse brain. Levels of CART-IR in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), and hypothalamic paraventricular nucleus (PVN) were significantly increased before the test swim by desipramine and citalopram treatments. This increase in CART-IR in the AcbSh, dBNST, and PVN before the test swim remained elevated by desipramine treatment after the test swim, but this increase in these brain areas returned to near control levels after test swim by citalopram treatment. Citalopram, but not desipramine, treatment increased levels of CART-IR in the central nucleus of the amygdala (CeA) and the locus ceruleus (LC) before the test swim, and this increase was returned to control levels after the test swim in the CeA, but not in the LC. These results suggest common and distinct regulation of CART by desipramine and citalopram treatments in the FST and raise the possibility that CART in the AcbSh, dBNST, and CeA may be involved in antidepressant-like effect in the FST.

  8. Muscle forces during locomotion in kangaroo rats: force platform and tendon buckle measurements compared.

    PubMed

    Biewener, A A; Blickhan, R; Perry, A K; Heglund, N C; Taylor, C R

    1988-07-01

    The muscle forces and stresses occurring during normal locomotor activity in kangaroo rats are compared with the peak isometric force developed by the same muscles in situ. Two methods were used simultaneously to determine the stresses (force/cross-sectional area) acting in the ankle extensors during steady-speed hopping and during jumps when animals were startled: a direct measurement using a force buckle surgically implanted around a tendon; and an indirect measurement using a force platform/ciné analysis technique. We obtained essentially the same values with the two techniques. We found that at slow speeds (0.7 m s-1) the ankle extensor muscles of kangaroo rats exerted 20% of the maximum isometric force developed when the muscles were stimulated via the tibial nerve. This increased to 53% at higher speeds (1.9 m s-1). At the animals's preferred hopping speed (1.5 m s-1), peak force was approximately 40% of maximum isometric force. In jumps when animals were startled, peak forces as high as 175% of the maximal elicited isometric force were recorded. These high forces always occurred when the muscles were being stretched. It appears that kangaroo rats utilize nearly the entire range of muscle force possible during normal locomotor events (i.e. up to 175% of maximum isometric force when muscles are stretched).

  9. Changes in force production and stroke parameters of trained able-bodied and unilateral arm-amputee female swimmers during a 30 s tethered front-crawl swim.

    PubMed

    Lee, Casey Jane; Sanders, Ross H; Payton, Carl J

    2014-01-01

    This study examined changes in the propulsive force and stroke parameters of arm-amputee and able-bodied swimmers during tethered swimming. Eighteen well-trained female swimmers (nine unilateral arm amputees and nine able-bodied) were videotaped performing maximal-effort 30 s front-crawl swims, while attached to a load cell mounted on a pool wall. Tether force, stroke rate, stroke phase durations and inter-arm angle were quantified. The able-bodied group produced significantly higher mean and maximum tether forces than the amputee group. The mean of the intra-cyclic force peaks was very similar for both groups. Mean and maximum tether force had significant negative associations with 100 m swim time, for both groups. Both groups exhibited a similar fatigue index (relative decrease in tether force) during the test, but the amputees had a significantly greater stroke rate decline. A significant positive association between stroke rate decline and fatigue index was obtained for the able-bodied group only. Inter-arm angle and relative phase durations did not change significantly during the test for either group, except the recovery phase duration of the arm amputees, which decreased significantly. This study's results can contribute to the development of a more evidence-based classification system for swimmers with a disability.

  10. Galanin impairs acquisition but not retrieval of spatial memory in rats studied in the Morris swim maze.

    PubMed

    Sundström, E; Archer, T; Melander, T; Hökfelt, T

    1988-06-01

    The effect of intraventricular administration of the neuropeptide galanin on acquisition and retrieval in a modified Morris swim maze was studied in rats. Galanin induced a significant deficit in the acquisition of the task while no effects on the retrieval were observed. No deficits were seen 24 h after the last treatment. Galanin did not increase the number of failures to reach the platform. It is suggested that endogenous galanin modulates learning possibly via the galanin-containing cholinergic neurons in the septum-basal forebrain area projecting to the hippocampus and cortex.

  11. Influence of sildenafil on the antidepressant activity of bupropion and venlafaxine in the forced swim test in mice.

    PubMed

    Socała, Katarzyna; Nieoczym, Dorota; Wyska, Elżbieta; Poleszak, Ewa; Wlaź, Piotr

    2012-12-01

    Recent studies highlight the involvement of the nitrergic system in the mechanism of action of antidepressant drugs. Sildenafil, a selective PDE5 inhibitor, was shown to abolish the anti-immobility effects of bupropion, venlafaxine and s-citalopram in mice. In this study we assessed the effects of sildenafil on the activity of bupropion and venlafaxine in the forced swim test in mice. Swim trials were conducted by placing mice in glass cylinders filled with water for 6min and the duration of the behavioral immobility during the last 4min of the test was evaluated. Locomotor activity was evaluated with photoresistor actimeters. Brain and serum concentrations of the studied antidepressants were determined by HPLC method. Sildenafil at a dose of 20mg/kg, but not 5 and 10mg/kg, significantly increased the anti-immobility action of bupropion (20mg/kg). The antidepressant activity of venlafaxine (2mg/kg) was potentiated by joint administration with sildenafil at doses of 10 and 20mg/kg. Since the combined treatments did not increase the locomotor activity, the antidepressant-like effects were not related to non-specific behavioral activation. Data from pharmacokinetic studies revealed that sildenafil increased bupropion and venlafaxine levels in serum without affecting their concentrations in the brain. The present study demonstrates the enhancement of anti-immobility action of bupropion and venlafaxine by sildenafil co-administration. The observed changes might have been partly due to pharmacokinetic interactions. However, mechanisms underlying the effects of sildenafil on the antidepressant activity of bupropion and venlafaxine should be carefully evaluated in further studies.

  12. The Impacts of Swimming Exercise on Hippocampal Expression of Neurotrophic Factors in Rats Exposed to Chronic Unpredictable Mild Stress

    PubMed Central

    Dang, Rui-Li; Zhang, Li-Hong; Xue, Ying; Tang, Mi-Mi

    2014-01-01

    Depression is associated with stress-induced neural atrophy in limbic brain regions, whereas exercise has antidepressant effects as well as increasing hippocampal synaptic plasticity by strengthening neurogenesis, metabolism, and vascular function. A key mechanism mediating these broad benefits of exercise on the brain is induction of neurotrophic factors, which instruct downstream structural and functional changes. To systematically evaluate the potential neurotrophic factors that were involved in the antidepressive effects of exercise, in this study, we assessed the effects of swimming exercise on hippocampal mRNA expression of several classes of the growth factors (BDNF, GDNF, NGF, NT-3, FGF2, VEGF, and IGF-1) and peptides (VGF and NPY) in rats exposed to chronic unpredictable mild stress (CUMS). Our study demonstrated that the swimming training paradigm significantly induced the expression of BDNF and BDNF-regulated peptides (VGF and NPY) and restored their stress-induced downregulation. Additionally, the exercise protocol also increased the antiapoptotic Bcl-xl expression and normalized the CUMS mediated induction of proapoptotic Bax mRNA level. Overall, our data suggest that swimming exercise has antidepressant effects, increasing the resistance to the neural damage caused by CUMS, and both BDNF and its downstream neurotrophic peptides may exert a major function in the exercise related adaptive processes to CUMS. PMID:25477997

  13. Swimming exercise ameliorates depression-like behavior in chronically stressed rats: relevant to proinflammatory cytokines and IDO activation.

    PubMed

    Liu, Weina; Sheng, Hui; Xu, Yongjun; Liu, Yu; Lu, Jianqiang; Ni, Xin

    2013-04-01

    Chronic stress is involved in development of depression and causes immune alterations. Indoleamine-2,3-dioxygenase (IDO) plays a pivotal role in mediating the depression-like behaviors in response to immune activation. Physical exercise has been shown to reduce the stress impairment and ameliorate depressive symptoms. The objectives of present study were to confirm that chronic unpredictable mild stress (CUMS) induces depression-like behavior and inflammatory responses within the brain, and then investigate whether swimming exercise alleviates the depression-like behaviors induced by CUMS through proinflammatory cytokine-induced alteration of IDO in brain. It has been found that CUMS exposure induced depression-like behavior, increased serum corticosterone (CORT) level, decreased 5-HT level, increased IFN-γ and TNF-α levels and elevated IDO activity in prefrontal cortex. Moreover, the level of 5-HT was inversely correlated with IDO level. Regular swimming exercise ameliorated depressive symptoms induced by CUMS. The exercise reduced serum CORT level, increased 5-HT level as well as decreased levels of IFN-γ, TNF-α and IDO in prefrontal cortex in CUMS rats. These findings suggested that CUMS activate HPA axis and induce immune activation, which may stimulate IDO activity, leading to the reduction of 5-HT level in brain, thereby resulting in depression. Swimming exercise may inhibit activation of inflammation/IDO pathways induced by CUMS, thereby ameliorating depression.

  14. The impacts of swimming exercise on hippocampal expression of neurotrophic factors in rats exposed to chronic unpredictable mild stress.

    PubMed

    Jiang, Pei; Dang, Rui-Li; Li, Huan-De; Zhang, Li-Hong; Zhu, Wen-Ye; Xue, Ying; Tang, Mi-Mi

    2014-01-01

    Depression is associated with stress-induced neural atrophy in limbic brain regions, whereas exercise has antidepressant effects as well as increasing hippocampal synaptic plasticity by strengthening neurogenesis, metabolism, and vascular function. A key mechanism mediating these broad benefits of exercise on the brain is induction of neurotrophic factors, which instruct downstream structural and functional changes. To systematically evaluate the potential neurotrophic factors that were involved in the antidepressive effects of exercise, in this study, we assessed the effects of swimming exercise on hippocampal mRNA expression of several classes of the growth factors (BDNF, GDNF, NGF, NT-3, FGF2, VEGF, and IGF-1) and peptides (VGF and NPY) in rats exposed to chronic unpredictable mild stress (CUMS). Our study demonstrated that the swimming training paradigm significantly induced the expression of BDNF and BDNF-regulated peptides (VGF and NPY) and restored their stress-induced downregulation. Additionally, the exercise protocol also increased the antiapoptotic Bcl-xl expression and normalized the CUMS mediated induction of proapoptotic Bax mRNA level. Overall, our data suggest that swimming exercise has antidepressant effects, increasing the resistance to the neural damage caused by CUMS, and both BDNF and its downstream neurotrophic peptides may exert a major function in the exercise related adaptive processes to CUMS. PMID:25477997

  15. Expression of the Mir-133 and Bcl-2 could be affected by swimming training in the heart of ovariectomized rats

    PubMed Central

    Habibi, Parisa; Alihemmati, Alireza; NourAzar, Alireza; Yousefi, Hadi; Mortazavi, Safieh; Ahmadiasl, Nasser

    2016-01-01

    Objective(s): The beneficial and more potent role of exercise to prevent heart apoptosis in ovariectomized rats has been known. The aim of this study was to examine the effects of swimming training on cardiac expression of Bcl-2, and Mir-133 levels and glycogen changes in the myocyte. Materials and Methods: Forty animals were separated into four groups as control, sham, ovariectomy (OVX) and ovariectomized group with 8 weeks swimming training (OVX.E). Training effects were evaluated by measuring lipid profiles, Bcl-2 and Mir-133 expression levels in the cardiac tissue. Grafts were analyzed by reverse transcription–polymerase chain reaction for Bcl-2 mRNA and Mir-133 and by Western blot for Bcl-2 protein. Results: Ovariectomy down-regulated Bcl-2 and Mir-133 expression levels in the cardiac tissue, and swimming training up-regulated their expression significantly (P<0.05). Conclusion: Our results showed that regular exercise as a physical replacement therapy could prevent and improve the effects of estrogen deficiency in the cardia. PMID:27279981

  16. Sildenafil, a phosphodiesterase type 5 inhibitor, enhances the activity of two atypical antidepressant drugs, mianserin and tianeptine, in the forced swim test in mice.

    PubMed

    Socała, Katarzyna; Nieoczym, Dorota; Wyska, Elżbieta; Poleszak, Ewa; Wlaź, Piotr

    2012-08-01

    Sildenafil, a selective phosphodiesterase type 5 inhibitor, has recently been reported to abolish anti-immobility action of antidepressant drugs, i.e., bupropion, venlafaxine and S-citalopram, in the forced swim test in mice. The present study was designed to investigate the influence of sildenafil on the potential of two atypical antidepressants, namely mianserin and tianeptine. Swim sessions were conducted by placing mice in glass cylinders filled with water for 6 min and the duration of the behavioral immobility during the last 4 min of the test was evaluated. Locomotor activity was measured with photoresistor actimeters. To evaluate the potential pharmocokinetic interaction, total brain concentrations of the studied antidepressants were determined by HPLC method. Sildenafil at a dose of 2.5 mg/kg did not affect the activity of mianserin (20 mg/kg) in the forced swim test. Interestingly, at higher doses (5 and 10 mg/kg), sildenafil significantly enhanced the anti-immobility action of mianserin. Likewise, sildenafil (5, 10 and 20 mg/kg) robustly augmented the antidepressant activity of tianeptine (30 mg/kg). Mianserin alone, as well as in a combination with sildenafil at the highest dose, caused a potent reduction in locomotor activity. However, the changes in motor activity did not interfere with the data obtained in the forced swim test. Sildenafil significantly increased the total brain tianeptine concentration. No alteration in mianserin level in the brain after sildenafil co-administration was observed. The present study suggests that sildenafil enhances the activity of mianserin and tianeptine in the forced swim test in mice. The changes in the antidepressant activity of mianserin evoked by sildenafil co-administration were related to pharmacodynamic interaction while the interaction between tianeptine and sildenafil was, at least in part, pharmacokinetic in nature.

  17. Sildenafil, a phosphodiesterase type 5 inhibitor, enhances the activity of two atypical antidepressant drugs, mianserin and tianeptine, in the forced swim test in mice.

    PubMed

    Socała, Katarzyna; Nieoczym, Dorota; Wyska, Elżbieta; Poleszak, Ewa; Wlaź, Piotr

    2012-08-01

    Sildenafil, a selective phosphodiesterase type 5 inhibitor, has recently been reported to abolish anti-immobility action of antidepressant drugs, i.e., bupropion, venlafaxine and S-citalopram, in the forced swim test in mice. The present study was designed to investigate the influence of sildenafil on the potential of two atypical antidepressants, namely mianserin and tianeptine. Swim sessions were conducted by placing mice in glass cylinders filled with water for 6 min and the duration of the behavioral immobility during the last 4 min of the test was evaluated. Locomotor activity was measured with photoresistor actimeters. To evaluate the potential pharmocokinetic interaction, total brain concentrations of the studied antidepressants were determined by HPLC method. Sildenafil at a dose of 2.5 mg/kg did not affect the activity of mianserin (20 mg/kg) in the forced swim test. Interestingly, at higher doses (5 and 10 mg/kg), sildenafil significantly enhanced the anti-immobility action of mianserin. Likewise, sildenafil (5, 10 and 20 mg/kg) robustly augmented the antidepressant activity of tianeptine (30 mg/kg). Mianserin alone, as well as in a combination with sildenafil at the highest dose, caused a potent reduction in locomotor activity. However, the changes in motor activity did not interfere with the data obtained in the forced swim test. Sildenafil significantly increased the total brain tianeptine concentration. No alteration in mianserin level in the brain after sildenafil co-administration was observed. The present study suggests that sildenafil enhances the activity of mianserin and tianeptine in the forced swim test in mice. The changes in the antidepressant activity of mianserin evoked by sildenafil co-administration were related to pharmacodynamic interaction while the interaction between tianeptine and sildenafil was, at least in part, pharmacokinetic in nature. PMID:22406168

  18. Swim Training Improves HOMA-IR in Type 2 Diabetes Induced by High Fat Diet and Low Dose of Streptozotocin in Male Rats

    PubMed Central

    Ghiasi, Rafigheh; Ghadiri Soufi, Farhad; Somi, Mohammad hossein; Mohaddes, Gisou; Mirzaie Bavil, Fariba; Naderi, Roya; Alipour, Mohammad Reza

    2015-01-01

    Purpose: Insulin resistance plays a key role in the onset and development of type 2 diabetes mellitus (T2DM) and its complications. In this study, we evaluated the effect of swim training on insulin resistance in diabetic rats. Methods: Forty male Wistar rats were randomly divided into four groups (n=10): sedentary control (Con), sedentary diabetic (Dia), swim trained control (Exe) and swim trained diabetic (Dia+Exe) rats. Diabetes was induced by high fat diet (HFD) and a low dose of streptozotocin (35 mg/kg, i.p). In trained groups, one week after the induction of diabetes, animals were subjected to swimming (60 min/5 days a week) for 10 weeks. At the end of training, fasting blood sugar (FBS), oral glucose tolerance test (OGTT), fasting/basal insulin, glycosylated hemoglobin (HbA1c) levels, insulin resistance index, homeostasis model assessment method (HOMA-IR), triglycerides (TG,) total cholesterol (TCh), and high density lipoprotein (HDL) levels in blood were measured. Results: Swimming significantly improved OGTT (P<0.01) and HOMA-IR (P<0.01). Swim training also significantly decreased FBS (p<0.01), fasting/basal insulin (P<0.01), HbA1C (p<0.01), TG (P<0.05), and TCh (P<0.05) levels. It also significantly increased HDL (p<0.05) level. Conclusion: Our findings indicate that swim training improved glycemic control and insulin sensitivity in type 2 diabetes caused by high fat diet in male rats. PMID:26504760

  19. [Maternal methyl-containing dietary supplementation alters the ability to learn in adult rats in swimming Morris test].

    PubMed

    Pliusnina, I Z; Os'kina, I N; Shchepina, O A; Prasolova, L A; Trut, L N

    2006-01-01

    Maternal choline diet influences the spatial learning processes. In this work, the learning ability of adult progeny of mothers who had received methyl diet enriched with choline and betain during pregnancy and lactation was studied in Morris test. The introduction of the diet to pregnant rats resulted in an increase in the time of search for invisible platform and time of swimming near the pool walls in offsprings, which meant a worsening of their learning ability. It was also found that change in platform searching strategy was not associated with an increase in anxiety of male rats. Possible involvement of maternal methyl diet in the change of expression of genes which control development of the nervous system is discussed. PMID:16869262

  20. Protective effects of forced exercise against methylphenidate-induced anxiety, depression and cognition impairment in rat

    PubMed Central

    Motaghinejad, Majid; Motevalian, Manijeh; Larijani, Setare Farokhi; Khajehamedi, Zohreh

    2015-01-01

    Background: Methylphenidate (MPH), a neural stimulant, can cause damages to brain; the chronic neurochemical and behavioral effects of MPH remain unclear. Exercise lowers stress and anxiety and can act as non-pharmacologic neuroprotective agent. In this study protective effects of exercise in MPH-induced anxiety, depression and cognition impairment were investigated. Materials and Methods: Seventy adult male rats were divided randomly into five groups. Group 1 served as negative control, received normal saline (0.2 ml/rat) for 21 days, group 2 and 3 (as positive controls) received MPH (10 and 20 mg/kg) for 21 days. Groups 4 and 5 concurrently were treated with MPH (10 and 20 mg/kg) and forced exercise for 21 days. On day 21, Elevated Plus Maze (EPM), Open Field Test (OFT), Forced Swim Test (FST) and Tail Suspension Test (TST) were used to investigate the level of anxiety and depression in animals. In addition between 17th and 21th days, Morris Water Maze (MWM) was applied to evaluate the effect of MPH on spatial learning and memory. Results: MPH-treated animals indicated a reflective depression and anxiety in a dose-dependent manner in FST, EPM and TST which were significantly different from the control group and also can significantly attenuate the motor activity and anxiety in OFT. Forced exercise by treadmill can attenuate MPH-induced anxiety, depression and motor activity alteration in OFT. MPH also can disturb learning and memory in MWM and forced exercise can neutralize this effect of MPH. Conclusion: We conclude that forced exercise can be protective in brain against MPH-induced anxiety, depression and cognition alteration. PMID:26322282

  1. The effect of acute swim stress and training in the water maze on hippocampal synaptic activity as well as plasticity in the dentate gyrus of freely moving rats: revisiting swim-induced LTP reinforcement.

    PubMed

    Tabassum, Heena; Frey, Julietta U

    2013-12-01

    Hippocampal long-term potentiation (LTP) is a cellular model of learning and memory. An early form of LTP (E-LTP) can be reinforced into its late form (L-LTP) by various behavioral interactions within a specific time window ("behavioral LTP-reinforcement"). Depending on the type and procedure used, various studies have shown that stress differentially affects synaptic plasticity. Under low stress, such as novelty detection or mild foot shocks, E-LTP can be transformed into L-LTP in the rat dentate gyrus (DG). A reinforcing effect of a 2-min swim, however, has only been shown in (Korz and Frey (2003) J Neurosci 23:7281-7287; Korz and Frey (2005) J Neurosci 25:7393-7400; Ahmed et al. (2006) J Neurosci 26:3951-3958; Sajikumar et al., (2007) J Physiol 584.2:389-400) so far. We have reinvestigated these studies using the same as well as an improved recording technique which allowed the recording of field excitatory postsynaptic potentials (fEPSP) and the population spike amplitude (PSA) at their places of generation in freely moving rats. We show that acute swim stress led to a long-term depression (LTD) in baseline values of PSA and partially fEPSP. In contrast to earlier studies a LTP-reinforcement by swimming could never be reproduced. Our results indicate that 2-min swim stress influenced synaptic potentials as well as E-LTP negatively.

  2. The role of 5-HT1A and 5-HT1B receptors in antidepressant drug actions in the mouse forced swimming test.

    PubMed

    Redrobe, J P; MacSweeney, C P; Bourin, M

    1996-12-30

    The forced swimming test is a behavioural model developed to predict the efficacy of antidepressant drugs. Few studies have been aimed at evaluating the mechanism of action of antidepressants in the forced swimming test. The present study was designed in order to further evaluate the mode of action of antidepressants in the forced swimming test, by using selective agonists and antagonists at 5-HT1A and 5-HT1B receptor sites. Agonists/antagonists and antidepressants were administered 45 min and 30 min, respectively, prior to testing. Prior administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1 mg/kg, i.p.) induced anti-immobility effects with the tricyclic antidepressant imipramine (8 mg/kg, i.p.) and noradrenaline uptake inhibitors maprotiline (8 mg/kg, i.p.) and desipramine (16 mg/kg, i.p.), but not with fluoxetine (16 mg/kg, i.p.), citalopram (16 mg/kg, i.p.) or fluvoxamine (8 mg/kg, i.p.). These effects were antagonised by prior administration of 1-(2-methoxyphenyl)-4-[-(2-phthalimido)butyl]piperazine) (NAN 190) (0.5 mg/kg, i.p.). On the other hand, pretreatment with (+/-)-pindolol (32 mg/kg, i.p.) potentiated the effects of the selective serotonin reuptake inhibitors and was devoid of any activity with imipramine (8 mg/kg, i.p.), maprotiline (8 mg/kg, i.p.) or desipramine (16 mg/kg, i.p.). Prior administration of 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU 24969) enhanced the antidepressant-like effects of the selective serotonin reuptake inhibitors and imipramine (8 mg/kg, i.p.) in the forced swimming test. The anti-immobility effects of the selective serotonin reuptake inhibitors in the forced swimming test seem to be mediated by presynaptic 5-HT1A receptors as well as postsynaptic 5-HT1B receptors. Antidepressant-like effects of the noradrenaline uptake inhibitors seem, on the other hand, to be mediated by postsynaptic 5-HT1A receptors. Considering the variety of 5-HT receptors, it is possible that other subtypes may participate

  3. Effect of endurance swimming on rat cardiac myofibrillar ATPase with experimental diabetes.

    PubMed

    Belcastro, A N; Maybank, P; Rossiter, M; Secord, D

    1985-09-01

    Diabetes is characterized by depressed cardiac functional properties attributed to Ca2+-activated ATPase activity. In contrast, endurance swimming enhances the cardiac functional properties and Ca2+-activated myofibril ATPase. Thus, the purpose of this study was to observe if the changes associated with experimental diabetes can be ameliorated with training. Diabetes was induced with a single i.v. injection of streptozotocin (60 mg/kg). Blood and urine glucose concentrations were 802 +/- 44 and 6965 +/- 617 mg/dL, respectively. The training control and training diabetic animals were made to swim (+/- 2% body weight) 4 days/week for 8 weeks. Cardiac myofibril, at 10 microM free Ca2+ concentration was reduced by 54% in the sedentary diabetics compared with sedentary control animals (p less than 0.05). Swim training enhanced the Ca2+-activated myofibril ATPase activities for the normal animals. The diabetic animals, which swam for 8 weeks, had further reduced their Ca2+-activated myofibril ATPase activity when compared with sedentary diabetics (p less than 0.05). Similarly, the Mg2+-stimulated myofibril ATPase activity was depressed by 31% in diabetics following endurance swimming. It is concluded that the depressed Ca2+-activated myofibril ATPase activity of diabetic hearts is not reversible with endurance swimming. PMID:2932207

  4. A Computational Fluid Dynamics Analysis of Hydrodynamic Force Acting on a Swimmer’S Hand in a Swimming Competition

    PubMed Central

    Sato, Yohei; Hino, Takanori

    2013-01-01

    A stroke-analysis system based on a CFD (Computational Fluid Dynamics) simulation has been developed to evaluate the hydrodynamic forces acting on a swimmer’s hand. Using the present stroke-analysis system, a stroke technique of top swimmers can be recognized with regard to the hydrodynamic forces. The developed analysis system takes into account the effect of a transient stroke motion including acceleration and a curved stroke path without using assumptions such as a quasi-static approach. An unsteady Navier-Stokes solver based on an unstructured grid method is employed as the CFD method to calculate a viscous flow around a swimmer’s hand which can cope with the complicated geometry of hands. The CFD method is validated by comparison with experiments in steady-state and transient conditions. Following the validations, a stroke-analysis system is proposed, in which a hand moves in accordance with a stroke path measured by synchronized video cameras, and the fluid forces acting on the hand are computed with the CFD method. As a demonstration of the stroke-analysis system, two world class swimmers’ strokes in a race of 200 m freestyle are analyzed. The hydrodynamic forces acting on the hands of the top swimmers are computed, and the comparison of two swimmers shows that the stroke of the faster swimmer, who advanced at 1.84 m·s-1 during the stroke-analysis, generated larger thrust with higher thrust efficiency than that of the slower swimmer, who advanced at 1.75 m·s-1. The applicability of the present stroke analysis system has been proved through this analysis. Key Points The stroke-analysis system using CFD technique has been established. The stroke path and the hand orientation are obtained from a swimming competition with two synchronized underwater video camera, and used for the input data to the CFD analysis. The hydrodynamic force acting on the swimmer’s hand and thrust efficiency are analyzed, and the stroke technique can be evaluated. PMID

  5. A computational fluid dynamics analysis of hydrodynamic force acting on a swimmer's hand in a swimming competition.

    PubMed

    Sato, Yohei; Hino, Takanori

    2013-01-01

    A stroke-analysis system based on a CFD (Computational Fluid Dynamics) simulation has been developed to evaluate the hydrodynamic forces acting on a swimmer's hand. Using the present stroke-analysis system, a stroke technique of top swimmers can be recognized with regard to the hydrodynamic forces. The developed analysis system takes into account the effect of a transient stroke motion including acceleration and a curved stroke path without using assumptions such as a quasi-static approach. An unsteady Navier-Stokes solver based on an unstructured grid method is employed as the CFD method to calculate a viscous flow around a swimmer's hand which can cope with the complicated geometry of hands. The CFD method is validated by comparison with experiments in steady-state and transient conditions. Following the validations, a stroke-analysis system is proposed, in which a hand moves in accordance with a stroke path measured by synchronized video cameras, and the fluid forces acting on the hand are computed with the CFD method. As a demonstration of the stroke-analysis system, two world class swimmers' strokes in a race of 200 m freestyle are analyzed. The hydrodynamic forces acting on the hands of the top swimmers are computed, and the comparison of two swimmers shows that the stroke of the faster swimmer, who advanced at 1.84 m·s(-1) during the stroke-analysis, generated larger thrust with higher thrust efficiency than that of the slower swimmer, who advanced at 1.75 m·s(-1). The applicability of the present stroke analysis system has been proved through this analysis. Key PointsThe stroke-analysis system using CFD technique has been established.The stroke path and the hand orientation are obtained from a swimming competition with two synchronized underwater video camera, and used for the input data to the CFD analysis.The hydrodynamic force acting on the swimmer's hand and thrust efficiency are analyzed, and the stroke technique can be evaluated. PMID:24421727

  6. Repeated forced swim stress enhances CFA-evoked thermal hyperalgesia and affects the expressions of pCREB and c-Fos in the insular cortex.

    PubMed

    Imbe, H; Kimura, A; Donishi, T; Kaneoke, Y

    2014-02-14

    Stress affects brain activity and promotes long-term changes in multiple neural systems. Exposure to stressors causes substantial effects on the perception and response to pain. In several animal models, chronic stress produces lasting hyperalgesia. The insular (IC) and anterior cingulate cortices (ACC) are the regions exhibiting most reliable pain-related activity. And the IC and ACC play an important role in pain modulation via the descending pain modulatory system. In the present study we examined the expression of phospho-cAMP response element-binding protein (pCREB) and c-Fos in the IC and ACC after forced swim stress (FS) and complete Freund's adjuvant (CFA) injection to clarify changes in the cerebral cortices that affect the activity of the descending pain modulatory system in the rats with stress-induced hyperalgesia. FS (day 1, 10min; days 2-3, 20min) induced an increase in the expression of pCREB and c-Fos in the anterior IC (AIC). CFA injection into the hindpaw after the FS shows significantly enhanced thermal hyperalgesia and induced a decrease in the expression of c-Fos in the AIC and the posterior IC (PIC). Quantitative image analysis showed that the numbers of c-Fos-immunoreactive neurons in the left AIC and PIC were significantly lower in the FS+CFA group (L AIC, 95.9±6.8; L PIC, 181.9±23.1) than those in the naive group (L AIC, 151.1±19.3, p<0.05; L PIC, 274.2±37.3, p<0.05). These findings suggest a neuroplastic change in the IC after FS, which may be involved in the enhancement of CFA-induced thermal hyperalgesia through dysfunction of the descending pain modulatory system.

  7. Swimming and the heart.

    PubMed

    Lazar, Jason M; Khanna, Neel; Chesler, Roseann; Salciccioli, Louis

    2013-09-20

    Exercise training is accepted to be beneficial in lowering morbidity and mortality in patients with cardiac disease. Swimming is a popular recreational activity, gaining recognition as an effective option in maintaining and improving cardiovascular fitness. Swimming is a unique form of exercise, differing from land-based exercises such as running in many aspects including medium, position, breathing pattern, and the muscle groups used. Water immersion places compressive forces on the body with resulting physiologic effects. We reviewed the physiologic effects and cardiovascular responses to swimming, the cardiac adaptations to swim training, swimming as a cardiac disease risk factor modifier, and the effects of swimming in those with cardiac disease conditions such as coronary artery disease, congestive heart failure and the long-QT syndrome.

  8. Involvement of NO/cGMP pathway in the antidepressant-like effect of gabapentin in mouse forced swimming test.

    PubMed

    Ostadhadi, Sattar; Kordjazy, Nastaran; Haj-Mirzaian, Arya; Ameli, Sanaz; Akhlaghipour, Golnoosh; Dehpour, AhmadReza

    2016-04-01

    Based on clinical studies regarding the beneficial effect of gabapentin in depression, we aimed to evaluate the antidepressant-like properties of gabapentin in mice and also the participation of nitric oxide (NO)/cyclic guanosine monophosphate pathway in this effect. The following drugs were used in this study: gabapentin; N(G)-nitro-L-arginine methyl ester (L-NAME), a non-specific NO synthase (NOS) inhibitor; 7-nitroindazole, a specific neuronal NOS inhibitor; aminoguanidine, a specific inducible NOS inhibitor; L-arginine, a NO precursor; and sildenafil, a phosphodiestrase inhibitor. Finally, we studied the behavioral effects through the forced swimming test (FST) and the changes of the hippocampus NO level through nitrite assay. The immobility time was significantly reduced after gabapentin administration. Co-administration of non-effective doses of gabapentin and L-NAME or 7-nitroindazole (7-NI) resulted in antidepressant-like effect in FST, while aminoguanidine did not affect the immobility time of gabapentin-treated mice. Furthermore, the antidepressant-like property of gabapentin was prevented by L-arginine or sildenafil. Also, the hippocampal nitrite level was significantly lower in gabapentin-treated mice relative to saline-injected mice, and co-administration of 7-NI with sub-effective gabapentin caused a significant decrease in hippocampal nitrite levels. Our results indicate that the antidepressant-like effect of gabapentin in the mice FST model is mediated at least in part through nitric oxide/cyclic guanosine monophosphate (cGMP) pathway.

  9. Is dopamine a limiting factor of the antidepressant-like effect in the mouse forced swimming test?

    PubMed

    Renard, Caroline E; Dailly, Eric; Nic Dhonnchadha, Bríd A; Hascoet, Martine; Bourin, Michel

    2004-12-01

    To study the role of dopamine (DA) in antidepressant-like effect in the forced swimming test (FST), the relationship between the magnitude of the antidepressant-like effect of drugs [citalopram, fluoxetine, paroxetine (selective serotonin reuptake inhibitors), desipramine (tricyclic antidepressant), maprotiline (tetracyclic antidepressant), bupropion (DA reuptake inhibitor), and tranylcypromine (inhibitor of monoamine oxidase)] and the corresponding concentration of DA in the whole brain of mice was investigated. A trend for an inversely proportional linear relationship [(magnitude of the antidepressant-like effect) = -0.0145 x (concentration of DA in the whole brain) +34.773 (r = 0.276)] was observed between the magnitude of the antidepressant-like effect and the concentrations of DA in the whole brain, but this correlation was not significant. This result suggests that the high concentration of DA in the whole brain could be a limiting factor for the antidepressant-like effect of antidepressants such as tranylcypromine and seems to play a minor role in the antidepressant-like activity of another antidepressant such as bupropion in the FST.

  10. Additive effects of lithium and antidepressants in the forced swimming test: further evidence for involvement of the serotoninergic system.

    PubMed

    Nixon, M K; Hascoet, M; Bourin, M; Colombel, M C

    1994-06-01

    In the mouse forced swimming test (FST) pretreatment with a subactive dose of lithium (1 mEq/kg), given IP 45 min before the test, facilitated the antidepressant activity of iprindole, fluoxetine, and moclobemide (given IP 30 min before the test). These antidepressants (ADS) were not active alone in the FST in this study. Moreover, when subactive lithium was combined with a wide range of ADS, each given at subactive doses, those ADS with serotoninergic properties (e.g. imipramine, citalopram, paroxetine, fluoxetine, trazodone, mianserin, and moclobemide) significantly reduced immobility times. ADS acting primarily on noradrenaline (NA) or dopamine (DA) systems (desipramine, maprotiline, viloxazine, and bupropion) did not significantly decrease immobility when given in combination with lithium. This was also the case for RO 16 6491 [a reversible, B specific monoamine oxidase inhibitor (MAOI)], nialamide, and pargyline (both irreversible, mixed MAOIs). The anti-immobility effect of iprindole in combination with lithium suggests either a direct or indirect action on the serotonin (5HT) system by this ADS whose mechanism of action remains obscure. These results, using an animal behavioral model of depression and combining our present knowledge of the acute action of various ADS, support the hypothesis that the potentiation by lithium of ADS is via direct 5HT mechanisms, indirectly via a NA/5HT link, and/or by second messenger systems. Lithium may also facilitate the expression of antidepressant activity of ADS not active by themselves in the FST.

  11. Evaluation of efficacies of different classes of antidepressants in the forced swimming test in mice at different ages.

    PubMed

    Bourin, M; Colombel, M C; Redrobe, J P; Nizard, J; Hascoët, M; Baker, G B

    1998-02-01

    1. The efficacies of different classes of antidepressants were investigated using the forced swimming test with mice at different ages. 2. Imipramine (4-32 mg/kg), desipramine (2-16 mg/kg) and bupropion (32, 64 mg/kg) showed activity in all age groups. 3. The selective serotonin reuptake inhibitors (SSRIs) citalopram (16 and 32 mg) and paroxetine (4 and 8 mg) were inactive in the oldest (40 weeks) group of mice, despite showing activity at the same doses in mice ranging in age from 4-24 weeks old. 4. Both SSRIs showed anti-immobility effects at low doses, (paroxetine: 1 and 2 mg/kg; citalopram: 4 and 8 mg/kg) in the 40-week old mice. These effects were not evident in the three younger groups of mice. 5. Moclobemide, a reversible selective inhibitor of monoamine oxidase-A, showed activity only at a high dose (128 mg/kg) and only in 12-week old animals. 6. Since SSRIs have been reported to have relatively selective effects on 5-HT1B receptors, the present results suggest that further studies comparing the effectiveness of SSRIs and other antidepressants in elderly patients should be done. Studies of the effects of aging on the density and/or affinity of 5-HT1A and 5-HT1B/1D receptors are also warranted.

  12. Stress-evoked tyrosine phosphorylation of signal regulatory protein α regulates behavioral immobility in the forced swim test.

    PubMed

    Ohnishi, Hiroshi; Murata, Takaaki; Kusakari, Shinya; Hayashi, Yuriko; Takao, Keizo; Maruyama, Toshi; Ago, Yukio; Koda, Ken; Jin, Feng-Jie; Okawa, Katsuya; Oldenborg, Per-Arne; Okazawa, Hideki; Murata, Yoji; Furuya, Nobuhiko; Matsuda, Toshio; Miyakawa, Tsuyoshi; Matozaki, Takashi

    2010-08-01

    Severe stress induces changes in neuronal function that are implicated in stress-related disorders such as depression. The molecular mechanisms underlying the response of the brain to stress remain primarily unknown, however. Signal regulatory protein alpha (SIRPalpha) is an Ig-superfamily protein that undergoes tyrosine phosphorylation and binds the protein tyrosine phosphatase Shp2. Here we show that mice expressing a form of SIRPalpha that lacks most of the cytoplasmic region manifest prolonged immobility (depression-like behavior) in the forced swim (FS) test. FS stress induced marked tyrosine phosphorylation of SIRPalpha in the brain of wild-type mice through activation of Src family kinases. The SIRPalpha ligand CD47 was important for such SIRPalpha phosphorylation, and CD47-deficient mice also manifested prolonged immobility in the FS test. Moreover, FS stress-induced tyrosine phosphorylation of both the NR2B subunit of the NMDA subtype of glutamate receptor and the K+-channel subunit Kvbeta2 was regulated by SIRPalpha. Thus, tyrosine phosphorylation of SIRPalpha is important for regulation of depression-like behavior in the response of the brain to stress.

  13. Impaired spatial performance in rats with retrosplenial lesions: importance of the spatial problem and the rat strain in identifying lesion effects in a swimming pool.

    PubMed

    Harker, K Troy; Whishaw, Ian Q

    2002-02-01

    Behavioral, electrophysiological, and anatomical evidence suggests that retrosplenial (RS) cortex (areas RSA and RSG) plays a role in spatial navigation. This conclusion has been questioned in recent work, suggesting that it is damage to the underlying cingulum bundle (CG) (areas CG and IG), and not RS, that disrupts spatial place learning (Aggleton et al., 2000). We revisited this issue by comparing Long-Evans rats, the strain used in studies that report RS deficits, to Dark Agouti rats, the strain in which no RS deficit has been reported. Rat groups with RS, RS + CG, or no lesion were tested on a place task in a swimming pool, a test of nonspatial and spatial learning, and a matching-to-place task, a relatively selective test of spatial learning. Long-Evans rats given RS and RS + CG lesions, either before or after training on the two tasks, were impaired on both tasks, a deficit not attributable to impaired visual acuity. Control Dark Agouti rats and RS Dark Agouti rats, although not different on the place task, were both significantly impaired relative to Long-Evans rats. The RS Dark Agouti group, however, was also impaired on the matching-to-place task. Thus, we show that RS cortex is part of an extended neural circuit involved in spatial behavior in both Long-Evans and Dark Agouti rats, but its role in the place task may be masked by an innate nonspatial deficit in Dark Agouti rats. The results are discussed in relation to the importance of assessing spatial learning with appropriate spatial tests, the problems of interpretation posed by rat strain differences, and the role of retrosplenial cortex in spatial behavior.

  14. Active drag, useful mechanical power output and hydrodynamic force coefficient in different swimming strokes at maximal velocity.

    PubMed

    Kolmogorov, S V; Duplishcheva, O A

    1992-03-01

    By comparing the time of the same distance swum with and without an added resistance, under the assumption of an equal power output in both cases, the drag of 73 top swimmers was estimated. The active drag Fr(a.d.) at maximal swimming velocities varied considerably across strokes and individuals. In the females Fr(a.d.) ranged from 69.78 to 31.16 N in the front-crawl, from 83.04 to 37.78 N in dolphin, from 93.56 to 45.19 N in breaststroke, and from 65.51 to 37.79 N in back-stroke. In the males Fr(a.d.) ranged from 167.11 to 42.23 N in front-crawl, from 156.09 to 46.95 N in dolphin, from 176.87 to 55.61 N in breaststroke, and from 146.28 to 46.36 N in back-stroke. Also, the ratio of Fr(a.d.) to the passive drag Fr(a.d.) as determined for the analogical velocity in a tugging condition (in standard body position-front gliding) shows considerable individual variations. In the female swimmers variations in Fr(a.d.)/Fr(p.d.) ranged from 145.17 to 59.94% in front-crawl, from 192.39 to 85.57% in dolphin, from 298.03 to 124.50% in breaststroke, and from 162.87 to 85.61% in back-stroke. In the male swimmers variations in Fr(a.d.)/Fr(p.d.) ranged from 162.24 to 62.39% in front-crawl, from 191.70 to 70.38% in dolphin, from 295.57 to 102.83% in breaststroke, and from 198.82 to 74.48% in back-stroke. The main reason for such variations is found in the individual features of swimming technique and can be quantitatively estimated with the hydrodynamic force coefficient, which thus provides an adequate index of technique. PMID:1564064

  15. Involvement of 5-HT(2C) receptors in the anti-immobility effects of antidepressants in the forced swimming test in mice.

    PubMed

    Clenet, F; De Vos, A; Bourin, M

    2001-04-01

    Several recent studies have demonstrated that 5-HT(1A), 5-HT(1B) and 5-HT(3) receptors were implicated in the mechanism of action of antidepressants in the mouse forced swimming test. Despite extensive evidence for a role of 5-HT(2C) receptors in depression, the precise role of these receptors in the effects of clinically established antidepressants was not directly investigated in the mouse forced swimming test. This work was aimed at exploring interactions between several doses of Ro 60-0175, a recently available, full and selective 5-HT(2C) agonist, and antidepressant drugs in the mouse forced swimming test. Spontaneous locomotor activity was measured as an index of intact sensorimotor functions and the dose-effect of Ro 60-0175 alone, as well as interactions with several antidepressants, such as tricyclic antidepressants (imipramine, desipramine and maprotiline) and selective serotonin reuptake inhibitors (paroxetine, citalopram, fluoxetine, fluvoxamine and sertraline), were studied in the mouse forced swimming test. There was no intrinsic antidepressant-like effect of Ro 60-0175, but an impairment in locomotor function was detected when using doses higher than 4 mg/kg in the mouse. There was a synergistic effect of low doses of Ro 60-0175 with sub-active doses of imipramine, paroxetine, citalopram and fluvoxamine; an antagonism between the highest dose of Ro 60-0175 and the active doses of paroxetine and fluoxetine was also detected. There is evidence that 5-HT(2C) receptors may be involved in the action of antidepressants which are able to boost the concentration of serotonin in the synapse, i.e. SSRIs and imipramine

  16. Possible involvement of nitric oxide (NO) signaling pathway in the antidepressant-like effect of MK-801(dizocilpine), a NMDA receptor antagonist in mouse forced swim test.

    PubMed

    Dhir, Ashish; Kulkarni, S K

    2008-03-01

    L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) is an important signaling pathway involved in depression. With this information, the present study aimed to study the involvement of this signaling pathway in the antidepressant-like action of MK-801 (dizocilpine; N-methyl-d-aspartate receptor antagonist) in the mouse forced-swim test. Total immobility period was recorded in mouse forced swim test for 6 min. MK-801 (5-25 microg/kg., ip) produced a U-shaped curve in reducing the immobility period. The antidepressant-like effect of MK-801 (10 microg/kg, ip) was prevented by pretreatment with L-arginine (750 mg/kg, ip) [substrate for nitric oxide synthase (NOS)]. Pretreatment of mice with 7-nitroindazole (7-NI) (25 mg/kg, ip) [a specific neuronal nitric oxide synthase inhibitor] produced potentiation of the action of subeffective dose of MK-801 (5 microg/kg, ip). In addition, treatment of mice with methylene blue (10 mg/kg, ip) [direct inhibitor of both nitric oxide synthase and soluble guanylate cyclase] potentiated the effect of MK-801 (5 microg/kg, ip) in the forced-swim test. Further, the reduction in the immobility period elicited by MK-801 (10 microg/kg, ip) was also inhibited by pretreatment with sildenafil (5 mg/kg, ip) [phosphodiesterase 5 inhibitor]. The various modulators used in the study and their combination did not produce any changes in locomotor activity per se and in combination with MK-801. MK-801 however, at higher doses (25 microg/kg, ip) produced hyperlocomotion. The results demonstrated the involvement of nitric oxide signaling pathway in the antidepressant-like effect of MK-801 in mouse forced-swim test.

  17. The glucagon-like peptide 1 receptor agonist exendin-4 improves reference memory performance and decreases immobility in the forced swim test.

    PubMed

    Isacson, Ruben; Nielsen, Elisabet; Dannaeus, Karin; Bertilsson, Göran; Patrone, Cesare; Zachrisson, Olof; Wikström, Lilian

    2011-01-10

    We have earlier shown that the glucagon-like peptide 1 receptor agonist exendin-4 stimulates neurogenesis in the subventricular zone and excerts anti-parkinsonian behavior. The aim of this study was to assess the effects of exendin-4 treatment on hippocampus-associated cognitive and mood-related behavior in adult rodents. To investigate potential effects of exendin-4 on hippocampal function, radial maze and forced swim test were employed. The time necessary to solve a radial maze task and the duration of immobility in the forced swim test were significantly reduced compared to respective vehicle groups if the animals had received exendin-4 during 1-2weeks before testing. In contrast to the positive control imipramine, single administration of exendin-4 1h before the challenge in the forced swim test had no effect. Immunohistochemical analysis showed that the incorporation of bromodeoxyuridine, a marker for DNA synthesis, as well as doublecortin expression was increased in the hippocampal dentate gyrus following chronic treatment with exendin-4 compared to vehicle-treated controls. The neurogenic effect of exendin-4 on hippocampus was confirmed by quantitative PCR showing an upregulation of mRNA expression for Ki-67, doublecortin and Mash-1. Since exendin-4 significantly improves hippocampus-associated behavior in adult rodents, it may be a candidate for alleviation of mood and cognitive disorders.

  18. Effects of co-treatment with mirtazapine and low doses of risperidone on immobility time in the forced swimming test in mice.

    PubMed

    Rogóż, Zofia

    2010-01-01

    The aim of the present study was to examine the effect of mirtazapine (MIR) and risperidone (an atypical antipsychotic drug), given separately or jointly, on immobility time in the forced swimming test in male C57BL/6J mice. Fluoxetine (FLU) was used as a reference drug. MIR (2.5, 5 and 10 mg/kg) and FLU (5 and 10 mg/kg), or risperidone in low doses (0.05 and 0.1 mg/kg) given alone did not change the immobility time of mice in the forced swimming test. Joint administration of MIR (5 and 10 mg/kg) or FLU (10 mg/kg) and risperidone (0.1 mg/kg) produced antidepressant-like activity in the forced swimming test. WAY100636 (a 5-HT(1A) receptor antagonist) inhibited, while yohimbine (an α(2)-adrenergic receptor antagonist) potentiated the antidepressant-like effect induced by co-administration of MIR and risperidone. Active behavior in that test did not reflect an increase in general activity, since combined administration of antidepressants and risperidone failed to enhance the locomotor activity of mice. The obtained results indicate that risperidone applied in a low dose enhances the antidepressant-like activity of MIR and that, among other mechanisms, 5-HT(1A)-, and α(2)-adrenergic receptors may play a role in this effect.

  19. Combining restricted diet with forced or voluntary exercises improves hippocampal BDNF and cognitive function in rats.

    PubMed

    Alomari, Mahmoud A; Khabour, Omar F; Alzoubi, Karem H; Alzubi, Mohammad A

    2016-01-01

    Dietary restriction (RDt) and exercise (Ex) enhances cognitive function due, at least in part, levels of neurotrophins such as brain-derived neurotrophic factor (BDNF). This study examined changes in BDNF levels and data acquisition and retention following every-other-day RDt alone, and combined with either voluntary wheel (VxRDt) or forced swimming Exs (FxRDt) in rats. Hippocampal BDNF was measured using ELISA while learning and memory formation were assessed with the radial arm water maze (RAWM) paradigm. After 6 weeks, VxRDt and FxRDt enhanced BDNF levels, and short- and long-term memories (p < 0.05). The magnitude of the increase in BDNF was significantly higher in VxRDt group than in other groups (p < 0.05). However, no differences were found in learning and memory formation between the Ex regiments (VxRDt versus FxRDt). Additionally, RDt alone neither modulated BDNF level nor enhanced learning and memory formation (p > 0.05). These results suggest more important role of Ex, as opposed to RDt, in enhancing learning and memory formation. In addition, VxRDt appears to be more potent in enhancing brain BDNF levels than FxRDt, when combined with RDt in rats. PMID:26000806

  20. The effect of the potassium channel activator, cromakalim, on antidepressant drugs in the forced swimming test in mice.

    PubMed

    Redrobe, J P; Pinot, P; Bourin, M

    1996-01-01

    The forced swimming test (FST) is a widely used behavioural model to predict potential antidepressant (AD) action of compounds in humans. It has been previously shown that pretreatment with lithium, quinine and clonidine had additive effects on AD drugs in the FST, an effect proposed to be a result of potassium channel blockade. It is possible that pretreatment with potassium channel openers may induce opposite effects to those seen following pretreatment with potassium channel blockers in the FST. Pretreatment with cromakalim (CROM) (1 mg/kg, intraperitoneally [i.p.]) antagonized the anti-immobility effect of the mixed noradrenaline (NA)/5-hydroxytryptamine (5-HT) reuptake inhibitors imipramine and amitriptyline (P < 0.05). CROM administration (0.06 and 1 mg/kg, i.p.) also blocked the AD-like effects of the specific NA reuptake inhibitor, desipramine, and the selective serotonin reuptake inhibitor, paroxetine (P < 0.05 and P < 0.01, respectively). Pretreatment with CROM via gavage (1 mg/kg) antagonized the AD-like effects of imipramine, amitiptyline, desipramine and paroxetine. CROM treatment (via i.p. route or gavage) did not have any significant effect on the anti-immobility activity of the atypical AD mianserin at any of the doses employed. Another potassium channel opener, minoxidil (MINOX), which does not cross the blood-brain barrier, was also tested to eliminate the possibility that CROM may be acting via peripheral/local mechanisms. MINOX (32 mg/kg) failed to antagonize anti-immobility effects of any of the AD tested. In conclusion, the results of the present study suggest that CROM is only acting on drugs involved with neurotransmitter uptake inhibition.

  1. Additive effects of glyburide and antidepressants in the forced swimming test: evidence for the involvement of potassium channel blockade.

    PubMed

    Guo, W; Todd, K; Bourin, M; Hascoet, M; Kouadio, F

    1996-08-01

    Evidence in the literature suggests that the modulatory effects of antidepressant drugs (ADS) on neuronal excitability, via the inhibition of K+ channels, may be the final common pathway of pharmacological action. Therefore, we tested the hypothesis that combining the ATP-sensitive K+ channel blocker glyburide with a variety of ADS would produce an additive effect and decrease the immobility time of mice in the forced swimming test (FST). Glyburide (GLY, IP, 30 and 50 mg/kg) and subactive doses of ADS were administered 45 and 30 min, respectively, prior to behavioral testing. Results showed that when combined with GLY, ADS whose main pharmacological effect is one of 5-HT uptake blockade (imipramine, amitriptyline, citalopram, paroxetine, fluoxetine, and fluvoxamine) were more effective in decreasing the amount of time mice were immobile, than when these drugs were administered alone. Some noradrenaline uptake inhibiting ADS (desipramine and viloxazine, but not maprotiline) were also significantly more effective in decreasing immobility time when combined with GLY than when administered alone. Pretreatment with GLY was found to have no effect on the dopamine uptake inhibitor bupropion, and out of the atypical ADS tested (trazodone, mianserine and iprindole), only coadministration with iprindole decreased the immobility time. Only the specific MAO-A inhibitor moclobemide was observed to have an antiimmobility effect when combined with GLY. Neither MAO-B specific (RO 16 6491) nor mixed MAO inhibitors (nialamide and pargyline) interacted with GLY to produce antiimmobility effects. These results corroborate and extend our previous report of the ADS enhancing effects of quinine in the same behavioral model, and suggest that the additive effects of quinine and GLY on ADS in FST are a result of K+ channel blockade.

  2. Antidepressant-like effects of Sanyuansan in the mouse forced swim test, tail suspension test, and chronic mild stress model.

    PubMed

    Yan, Shuo; You, Zi-Li; Zhao, Qiu-Ying; Peng, Cheng; He, Gang; Gou, Xiao-Jun; Lin, Bin

    2015-12-01

    Natural products have been widely reported as effective therapeutic alternatives for treatment of depression. Sanyuansan is a compound recipe composed of ginseng total saponins, fish oil, and valeriana. The aims of this study were to validate whether Sanyuansan has antidepressant-like effects through acute behavioral tests including the forced swimming test (FST), tail suspension test (TST), locomotor activity test, and chronic mild stress (CMS) mice model of depression. C57BL/6 mice were given oral administration of 30 mg/kg imipramine, Sanyuansan, and saline, respectively. The acute behavioral tests including the TST, FST, and locomotor activity test were done after the administration of drugs for consecutively three times (24 hours, 1 hour, and 0.5 hour prior to the tests). Furthermore, the sucrose preference and the serum corticosterone level of mice in the CMS model were examined. Sanyuansan only at 900 mg/kg markedly reduced immobility time in the TST compared with the saline-treated group of mice. Sanyuansan at doses of 225 mg/kg, 450 mg/kg, and 900 mg/kg significantly reduced immobility time of mice in the FST. Sanyuansan reversed the CMS-induced anhedonia and hyperactivation of the hypothalamus-pituitary-adrenal axis. In addition, our results showed that neither imipramine nor Sanyuansan at any dosage increased spontaneous motor activity. These results suggested that Sanyuansan induced significant antidepressant-like effects in mice in both acute and chronic animal models, which seemed unlikely to be attributed to an increase in locomotor activities of mice, and had no sedative-like effects. PMID:26709221

  3. Effects of ifenprodil on the antidepressant-like activity of NMDA ligands in the forced swim test in mice.

    PubMed

    Poleszak, Ewa; Wośko, Sylwia; Serefko, Anna; Szopa, Aleksandra; Wlaź, Aleksandra; Szewczyk, Bernadeta; Nowak, Gabriel; Wlaź, Piotr

    2013-10-01

    Multiple pre-clinical and clinical studies clearly displayed implication of the NMDA receptors in development of depressive disorders since a variety of NMDA receptor antagonists exhibit an antidepressant-like effect. The main aim of our study was to assess the influence of ifenprodil - an allosteric modulator selectively binding at the NR2B subunit on the performance in the forced swim test in mice of various NMDA receptor ligands interacting with distinct components of the NMDA receptor complex. Ifenprodil at a dose of 10mg/kg enhanced the antidepressant-like effect of CGP 37849 (a competitive NMDA receptor antagonist, 0.312mg/kg), L-701,324 (an antagonist at glycine site, 1mg/kg), MK-801 (a non-competitive antagonist, 0.05mg/kg) and d-cycloserine (a partial agonist of a glycine site, 2.5mg/kg) but it did not shorten the immobility time of animals which concurrently received an inorganic modulator of the NMDA receptor complex, such as Zn(2+) (2.5mg/kg) or Mg(2+) (10mg/kg). On the other hand, the antidepressant-like effect of ifenprodil (20mg/kg) was reversed by N-methyl-d-aspartic acid (an agonist at the glutamate site, 75mg/kg) or d-serine (an agonist at the glycine site, 100nmol/mouse). In conclusion, the antidepressant-like potential of ifenprodil given concomitantly with NMDA ligands was either reinforced (in the case of both partial agonist and antagonists, except for magnesium and zinc) or diminished (in the case of conventional full agonists).

  4. Chronic exercise prevents repeated restraint stress-provoked enhancement of immobility in forced swimming test in ovariectomized mice.

    PubMed

    Han, Tae-Kyung; Lee, Jang-Kyu; Leem, Yea-Hyun

    2015-06-01

    We assessed whether chronic treadmill exercise attenuated the depressive phenotype induced by restraint stress in ovariectomized mice (OVX). Immobility of OVX in the forced swimming test was comparable to that of sham mice (CON) regardless of the postoperative time. Immobility was also no difference between restrained mice (exposure to periodic restraint for 21 days; RST) and control mice (CON) on post-exposure 2nd and 9th day, but not 15th day. In contrast, the immobility of ovariectomized mice with repeated stress (OVX + RST) was profoundly enhanced compared to ovariectomized mice-alone (OVX), and this effect was reversed by chronic exercise (19 m/min, 60 min/day, 5 days/week for 8 weeks; OVX + RST + Ex) or fluoxetine administration (20 mg/kg, OVX + RST + Flu). In parallel with behavioral data, the immunoreactivity of Ki-67 and doublecortin (DCX) in OVX was significantly decreased by repeated stress. However, the reduced numbers of Ki-67- and DCX-positive cells in OVX + RST were restored in response to chronic exercise (OVX + RST + Ex) and fluoxetine (OVX + RST + Flu). In addition, the expression pattern of cAMP response element-binding protein (CREB) and calcium-calmodulin-dependent kinase IV (CaMKIV) was similar to that of the hippocampal proliferation and neurogenesis markers (Ki-67 and DCX, respectively). These results suggest that menopausal depression may be induced by an interaction between repeated stress and low hormone levels, rather than a deficit in ovarian secretion alone, which can be improved by chronic exercise.

  5. Immobility stress induces depression-like behavior in the forced swim test in mice: effect of magnesium and imipramine.

    PubMed

    Poleszak, Ewa; Wlaź, Piotr; Kedzierska, Ewa; Nieoczym, Dorota; Wyska, Elzbieta; Szymura-Oleksiak, Joanna; Fidecka, Sylwia; Radziwoń-Zaleska, Maria; Nowak, Gabriel

    2006-01-01

    Previously, we demonstrated antidepressant-like effect of magnesium (Mg) in the forced swim test (FST). Moreover, the joint administration of Mg and imipramine (IMI) at ineffective doses per se, resulted in a potent reduction in the immobility time in this test. In the present study, we examined the effect of immobility stress (IS), and Mg and/or IMI administration on FST behavior. IS induced enhancement of immobility time, which was reversed by Mg or IMI at doses ineffective in non-stressed mice (10 mg/kg and 15 mg/kg, respectively). The joint administration of Mg and IMI was effective in both IS and non-stressed animals in FST. IS did not significantly alter locomotor activity, while IMI or Mg + IMI treatment in IS mice reduced this activity. We also measured serum and brain Mg, IMI and its metabolite desipramine (DMI) concentration in mice subjected to FST and injected with Mg + IMI, both restrained and non-restrained. In the present study we demonstrated a significant increase (by 68%) in the brain IMI and a slight, non-significant reduction in DMI concentration in IS + Mg + IMI + FST vs. Mg + IMI + FST groups, which might indicate the reduction in brain IMI metabolism. The IS-induced reduction in brain IMI metabolism did not participate in the activity in FST, since no differences in such activity were noticed between IS + Mg + IMI + FST and Mg + IMI + FST groups. The present data suggest that IS-induced increase in immobility time in FST is more sensitive for detection antidepressant-like activity. However, further studies are needed to examine the effect of other antidepressants in such an experimental paradigm.

  6. Antidepressant-like effects of Sanyuansan in the mouse forced swim test, tail suspension test, and chronic mild stress model.

    PubMed

    Yan, Shuo; You, Zi-Li; Zhao, Qiu-Ying; Peng, Cheng; He, Gang; Gou, Xiao-Jun; Lin, Bin

    2015-12-01

    Natural products have been widely reported as effective therapeutic alternatives for treatment of depression. Sanyuansan is a compound recipe composed of ginseng total saponins, fish oil, and valeriana. The aims of this study were to validate whether Sanyuansan has antidepressant-like effects through acute behavioral tests including the forced swimming test (FST), tail suspension test (TST), locomotor activity test, and chronic mild stress (CMS) mice model of depression. C57BL/6 mice were given oral administration of 30 mg/kg imipramine, Sanyuansan, and saline, respectively. The acute behavioral tests including the TST, FST, and locomotor activity test were done after the administration of drugs for consecutively three times (24 hours, 1 hour, and 0.5 hour prior to the tests). Furthermore, the sucrose preference and the serum corticosterone level of mice in the CMS model were examined. Sanyuansan only at 900 mg/kg markedly reduced immobility time in the TST compared with the saline-treated group of mice. Sanyuansan at doses of 225 mg/kg, 450 mg/kg, and 900 mg/kg significantly reduced immobility time of mice in the FST. Sanyuansan reversed the CMS-induced anhedonia and hyperactivation of the hypothalamus-pituitary-adrenal axis. In addition, our results showed that neither imipramine nor Sanyuansan at any dosage increased spontaneous motor activity. These results suggested that Sanyuansan induced significant antidepressant-like effects in mice in both acute and chronic animal models, which seemed unlikely to be attributed to an increase in locomotor activities of mice, and had no sedative-like effects.

  7. Desipramine restricts estral cycle oscillations in swimming.

    PubMed

    Contreras, C M; Martínez-Mota, L; Saavedra, M

    1998-10-01

    1. Desipramine (DMI) is a tricyclic antidepressant which reduces the immobility in rats forced to swim; however, it is unknown whether estral cycle phases impinge on DMI actions on immobility in daily swimming tests during several weeks. 2. In female wistar rats, vaginal smears taken before testing defined four estral phases. Afterwards, the authors assessed the latency for the first period of immobility in five-min forced swim tests practiced on 21-day DMI (DMI group), 21-day washout saline given after a 21-day DMI treatment (washout-saline group), or non-treated rats (control group). 3. We observed a longer latency for the first period of immobility in proestrus-estrus from the control and washout-saline groups. The 21-day treatment with DMI (2.1 mg/kg i.p., once a day) significantly (p < 0.001) increased the latency by about 160% from control regardless of the estral cycle phase. 4. It is concluded that proestrus-estrus relates to increased struggling behavior. DMI enhances struggling behavior independently of hormonal state.

  8. The effects of different types of pre-training on the rat's retention performance in a swim-to-platform task following administration of scopolamine.

    PubMed

    Caldji, C; Vanderwolf, C H

    1996-10-01

    Previous research has found that centrally acting antimuscarinic drugs strongly impair the acquisition of a variety of learned behaviors in rats but have little effect on these same behaviors if training is given prior to drug treatment. We gave groups of rats different types of pre-training followed by treatment with scopolamine hydrobromide and subsequent testing on a simple swim-to-platform test. Factors such as practice in swimming without a platform to escape to, or learning to swim to a platform in a different apparatus or even to the test platform located in a different place did not protect the rats from the behavioral disruption produced by scopolamine. However, five training trials on the specific swim-to-platform task used in the retention test afforded almost complete protection against the effect of scopolamine. It appears that the protective effect of pre-training is highly specific and does not involve acquisition of some type of general rule which might survive antimuscarinic blockade.

  9. Effects of swimming exercise on morphine-induced reward and behavioral sensitization in maternally-separated rat pups in the conditioned place preference procedure.

    PubMed

    Abad, Atiyeh Taghavi-Khalil; Miladi-Gorji, Hossein; Bigdeli, Imanollah

    2016-09-19

    This study was designed to examine the effects of swimming exercise during adolescence on morphine-induced conditioned place preference (CPP) and behavioral sensitization in maternally separated male and female rat pups. Male Wistar rats were allowed to mate with female virgin Wistar rats. Pups were separated from the dam daily for 180min during postnatal days 2-14. All pups were weaned on day 21.The exercising pups were allowed to swim (60min/d, five days per a week, for 30days) during adolescence. Then, rat pups were tested for behavioral sensitization and the CPP induced by morphine. Maternal separation produced a significant increase in morphine-induced CPP in both sexes, behavioral sensitization in male pups and tolerance to morphine-induced motor activity in female pups. Swimmer pups separated from the dam exhibited a decrease in morphine-induced CPP in both sexes and behavioral sensitization in male pups than those of their control pups. The present results have shown that swimming exercise during adolescence may exert a protective effect against morphine-induced reward and behavioral sensitization in adult male and female rats following maternal separation. PMID:27519931

  10. Swimming exercise changes hemodynamic responses evoked by blockade of excitatory amino receptors in the rostral ventrolateral medulla in spontaneously hypertensive rats.

    PubMed

    Ogihara, Cristiana A; Schoorlemmer, Gerhardus H M; Lazari, Maria de Fátima M; Giannocco, Gisele; Lopes, Oswaldo U; Colombari, Eduardo; Sato, Monica A

    2014-01-01

    Exercise training reduces sympathetic activity in hypertensive humans and rats. We hypothesized that the swimming exercise would change the neurotransmission in the rostral ventrolateral medulla (RVLM), a key region involved in sympathetic outflow, and hemodynamic control in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Bilateral injections of kynurenic acid (KYN) were carried out in the RVLM in sedentary- (S-) or exercised- (E-) SHR and WKY rats submitted to swimming for 6 weeks. Rats were α-chloralose anesthetized and artificially ventilated, with Doppler flow probes around the lower abdominal aorta and superior mesenteric artery. Injections into the RVLM were made before and after i.v. L-NAME (nitric oxide synthase, NOS, inhibitor). Injections of KYN into the RVLM elicited a major vasodilation in the hindlimb more than in the mesenteric artery in E-SHR compared to S-SHR, but similar decrease in arterial pressure was observed in both groups. Injections of KYN into the RVLM after i.v. L-NAME attenuated the hindlimb vasodilation evoked by KYN and increased the mesenteric vasodilation in E-SHR. Swimming exercise can enhance the hindlimb vasodilation mediated by peripheral NO release, reducing the activation of neurons with EAA receptors in the RVLM in SHR. PMID:24696852

  11. Differential effects of swimming training on neuronal calcium sensor-1 expression in rat hippocampus/cortex and in object recognition memory tasks.

    PubMed

    Drumond, Luciana Estefani; Mourão, Flávio Afonso Gonçalves; Leite, Hércules Ribeiro; Abreu, Renata Viana; Reis, Helton José; Moraes, Márcio Flávio Dutra; Pereira, Grace Schenatto; Massensini, André Ricardo

    2012-07-01

    Physical activity has been proposed as a behavioral intervention that improves learning and memory; nevertheless, the mechanisms underlying these health benefits are still not well understood. Neuronal Calcium Sensor-1 (NCS-1) is a member of a superfamily of proteins that respond to local Ca(2+) changes shown to have an important role in learning and memory. The aim of the present study was to investigate the effects of swimming training on NCS-1 levels in the rat brain after accessing cognitive performance. Wistar rats were randomly assigned to sedentary (SG) or exercised groups (EG). The EG was subject to forced swimming activity, 30 min/day, 5 days/week, during 8 weeks. Progressive load trials were performed in the first and last week in order to access the efficiency of the training. After the 8 week training protocol, memory performance was evaluated by the novel object preference and object location tasks. NCS-1 levels were measured in the cortex and hippocampus using immunoblotting. The EG performed statistically better for the spatial short-term memory (0.73 ± 0.01) when compared to the SG (0.63 ± 0.02; P<0.05). No statistically significant exercise-effect was observed in the novel object preference task (SG 0.65 ± 0.02 and EG 0.68 ± 0.02; p>0.05). In addition, chronic exercise promoted a significant increase in hippocampal NCS-1 levels (1.8 ± 0.1) when compared to SG (1.17 ± 0.08; P<0,05), but had no effect on cortical NCS-1 levels (SG 1.6 ± 0.1 and EG 1.5 ± 0.1; p>0.05). Results suggest that physical exercise would modulate the state of the neural network regarding its potential for plastic changes: physical exercise could be modulating NCS-1 in an activity dependent manner, for specific neural substrates, thus enhancing the cellular/neuronal capability for plastic changes in these areas; which, in turn, would differentially effect ORM task performance for object recognition and displacement.

  12. NK1 receptor antagonism lowers occupancy requirement for antidepressant-like effects of SSRIs in the gerbil forced swim test.

    PubMed

    Lelas, Snjezana; Li, Yu-Wen; Wallace-Boone, Tanya L; Taber, Matthew T; Newton, Amy E; Pieschl, Rick L; Davis, Carl D; Molski, Thaddeus F; Newberry, Kimberly S; Parker, Michael F; Gillman, Kevin W; Bronson, Joanne J; Macor, John E; Lodge, Nicholas J

    2013-10-01

    The known interactions between the serotonergic and neurokinin systems suggest that serotonin reuptake inhibitor (SSRIs) efficacy may be improved by neurokinin-1 receptor (NK1R) antagonism. In the current studies combination of a subeffective dose of an SSRI (0.3 mg/kg fluoxetine or 0.03 mg/kg citalopram) with a subeffective dose of an NK1R antagonist (0.3 mg/kg aprepitant or 1 mg/kg CP-122,721) produced efficacy in the gerbil forced swim test (FST). Serotonin transporter (SERT) occupancy produced by 1 mg/kg fluoxetine (lowest efficacious dose) was 52 ± 5% and was reduced to 29 ± 4% at 0.3 mg/kg, a dose that was efficacious in combination with 0.3 mg/kg aprepitant or 1 mg/kg CP-122,721; the corresponding NK1R occupancies were 79 ± 4% and 61 ± 4% for aprepitant and CP-122,721, respectively. For citalopram, SERT occupancy at the lowest efficacious dose (0.1 mg/kg) was 50 ± 4% and was reduced to 20 ± 5% at 0.03 mg/kg, a dose that was efficacious when combined with aprepitant (0.3 mg/kg). Aprepitant (10 mg/kg) augmented the serotonin elevation produced by fluoxetine (1 or 10 mg/kg) in the gerbil prefrontal cortex; i.e. NK1R antagonism can modulate serotonin responses. A novel orally-available dual-acting NK1R antagonist/SERT inhibitor BMS-795176 is described; gerbil Ki = 1.4 and 1 nM at NK1R and SERT, respectively. BMS-795176 was efficacious in the gerbil FST; efficacy was observed with 35 ± 3% SERT occupancy and 73 ± 3% NK1R occupancy. The interaction between NK1R antagonism and SERT inhibition to lower the SERT occupancy required for antidepressant-like efficacy suggests that BMS-795176 has the potential to improve efficacy with a reduction in SSRI-associated side effects. PMID:23770339

  13. Caffeine enhances the antidepressant-like activity of common antidepressant drugs in the forced swim test in mice.

    PubMed

    Szopa, Aleksandra; Poleszak, Ewa; Wyska, Elżbieta; Serefko, Anna; Wośko, Sylwia; Wlaź, Aleksandra; Pieróg, Mateusz; Wróbel, Andrzej; Wlaź, Piotr

    2016-02-01

    Caffeine is the most widely used behaviorally active drug in the world which exerts its activity on central nervous system through adenosine receptors. Worrying data indicate that excessive caffeine intake applies to patients suffering from mental disorders, including depression. The main goal of the present study was to evaluate the influence of caffeine on animals' behavior in forced swim test (FST) as well as the effect of caffeine (5 mg/kg) on the activity of six typical antidepressants, such as imipramine (15 mg/kg), desipramine (10 mg/kg), fluoxetine (5 mg/kg), paroxetine (0.5 mg/kg), escitalopram (2 mg/kg), and reboxetine (2.5 mg/kg). Locomotor activity was estimated to verify and exclude false-positive/negative results. In order to assess the influence of caffeine on the levels of antidepressant drugs studied, their concentrations were determined in murine serum and brains using high-performance liquid chromatography. The results showed that caffeine at a dose of 10, 20, and 50 mg/kg exhibited antidepressant activity in the FST, and it was not related to changes in locomotor activity in the animals. Caffeine at a dose of 5 mg/kg potentiated the activity of all antidepressants, and the observed effects were not due to the increase in locomotor activity in the animals. The interactions between caffeine and desipramine, fluoxetine, escitalopram, and reboxetine were exclusively of pharmacodynamic character, because caffeine did not cause any changes in the concentrations of these drugs neither in blood serum nor in brain tissue. As a result of joint administration of caffeine and paroxetine, an increase in the antidepressant drug concentrations in serum was observed. No such change was noticed in the brain tissue. A decrease in the antidepressant drug concentrations in brain was observed in the case of imipramine administered together with caffeine. Therefore, it can be assumed that the interactions caffeine-paroxetine and caffeine-imipramine occur at least in

  14. NK1 receptor antagonism lowers occupancy requirement for antidepressant-like effects of SSRIs in the gerbil forced swim test.

    PubMed

    Lelas, Snjezana; Li, Yu-Wen; Wallace-Boone, Tanya L; Taber, Matthew T; Newton, Amy E; Pieschl, Rick L; Davis, Carl D; Molski, Thaddeus F; Newberry, Kimberly S; Parker, Michael F; Gillman, Kevin W; Bronson, Joanne J; Macor, John E; Lodge, Nicholas J

    2013-10-01

    The known interactions between the serotonergic and neurokinin systems suggest that serotonin reuptake inhibitor (SSRIs) efficacy may be improved by neurokinin-1 receptor (NK1R) antagonism. In the current studies combination of a subeffective dose of an SSRI (0.3 mg/kg fluoxetine or 0.03 mg/kg citalopram) with a subeffective dose of an NK1R antagonist (0.3 mg/kg aprepitant or 1 mg/kg CP-122,721) produced efficacy in the gerbil forced swim test (FST). Serotonin transporter (SERT) occupancy produced by 1 mg/kg fluoxetine (lowest efficacious dose) was 52 ± 5% and was reduced to 29 ± 4% at 0.3 mg/kg, a dose that was efficacious in combination with 0.3 mg/kg aprepitant or 1 mg/kg CP-122,721; the corresponding NK1R occupancies were 79 ± 4% and 61 ± 4% for aprepitant and CP-122,721, respectively. For citalopram, SERT occupancy at the lowest efficacious dose (0.1 mg/kg) was 50 ± 4% and was reduced to 20 ± 5% at 0.03 mg/kg, a dose that was efficacious when combined with aprepitant (0.3 mg/kg). Aprepitant (10 mg/kg) augmented the serotonin elevation produced by fluoxetine (1 or 10 mg/kg) in the gerbil prefrontal cortex; i.e. NK1R antagonism can modulate serotonin responses. A novel orally-available dual-acting NK1R antagonist/SERT inhibitor BMS-795176 is described; gerbil Ki = 1.4 and 1 nM at NK1R and SERT, respectively. BMS-795176 was efficacious in the gerbil FST; efficacy was observed with 35 ± 3% SERT occupancy and 73 ± 3% NK1R occupancy. The interaction between NK1R antagonism and SERT inhibition to lower the SERT occupancy required for antidepressant-like efficacy suggests that BMS-795176 has the potential to improve efficacy with a reduction in SSRI-associated side effects.

  15. Analysis of swimming motions.

    NASA Technical Reports Server (NTRS)

    Gallenstein, J.; Huston, R. L.

    1973-01-01

    This paper presents an analysis of swimming motion with specific attention given to the flutter kick, the breast-stroke kick, and the breast stroke. The analysis is completely theoretical. It employs a mathematical model of the human body consisting of frustrums of elliptical cones. Dynamical equations are written for this model including both viscous and inertia forces. These equations are then applied with approximated swimming strokes and solved numerically using a digital computer. The procedure is to specify the input of the swimming motion. The computer solution then provides the output displacement, velocity, and rotation or body roll of the swimmer.

  16. Antidepressant-like activity of sildenafil following acute and subchronic treatment in the forced swim test in mice: effects of restraint stress and monoamine depletion.

    PubMed

    Socała, Katarzyna; Nieoczym, Dorota; Pieróg, Mateusz; Szuster-Ciesielska, Agnieszka; Wyska, Elżbieta; Wlaź, Piotr

    2016-10-01

    Sildenafil is a highly effective oral agent for the treatment of erectile dysfunction of multiple etiologies. Although in clinical practice sildenafil is often used in depressed patients, its influence on the pathophysiology of depression remains unclear. The aim of the present study was to evaluate the antidepressant-like activity following acute and subchronic treatment with sildenafil in naïve mice as well as in mice with reserpine- and restraint stress-induced depressive-like behavior. Since corticosterone is released in response to acute stress, we also aimed to assess the influence of sildenafil on serum corticosterone level in non-stressed and stressed animals. The antidepressant activity of sildenafil was assessed in the forced swim test. Corticosterone serum level was determined by using ELISA method, while brain and serum sildenafil level via HPLC method. Sildenafil administered acutely exerted an antidepressant-like effect. Subchronic (14 days) administration of sildenafil resulted only in a weak antidepressant-like effect when evaluated 24 h after the last dose. Acute but not subchronic sildenafil administration reversed the reserpine- and stress-induced immobility in the forced swim test. The lack of effects of sildenafil after subchronic treatment could have been related to its complete elimination from the brain within 24 h from the last injection. Interestingly, acute administration of sildenafil produced a marked increase in serum corticosterone level in both non-stressed and stressed animals. Sildenafil exerts differential effects in the forced swim test after acute and subchronic administration. Further studies on the antidepressant activity of sildenafil are required. PMID:27283174

  17. Antidepressant-like activity of liposomal formulation containing nimodipine treatment in the tail suspension test, forced swim test and MAOB activity in mice.

    PubMed

    Moreno, Lina Clara Gayoso E Almendra Ibiapina; Rolim, Hercília Maria Lins; Freitas, Rivelilson Mendes; Santos-Magalhães, Nereide Stela

    2016-09-01

    Previous studies have shown that intracellular calcium ion dysfunction may be an etiological factor in affective illness. Nimodipine (NMD) is a Ca(2+) channel blocker that has been extensively investigated for therapy of central nervous system (CNS) disorders. In this work, we have evaluated the antidepressant-like activity of nimodipine encapsulated into liposomes (NMD-Lipo) in mice through tail suspension and forced swim assays, as well as MAOB activity. During the tail suspension test, the administration of NMD-Lipo at 0.1, 1 and 10mg/kg was able to promote a reduction in the immobility time of animals greater than the positive control (imipramine). In the forced swim test, the immobility time of mice treated with NMD-Lipo was reduced. This reduction was significantly greater than that found in the animals treated with imipramine and paroxetine. This may suggest that NMD-Lipo provides more antidepressant-like activity than in positive controls. The groups that received a combination of liposomal NMD and antidepressant drugs showed lower immobility time than the groups, which were treated only with imipramine or paroxetine. The mice treated with the combination of NMD-Lipo and reserpine presented an increase in the time of immobility compared with animals treated only with NMD-Lipo. There was a significant decrease in MAOB activity in animals treated with NMD-Lipo compared with untreated animals. The results of the tail suspension test, forced swim test and MAOB activity suggested that the antidepressant activity of NMD-Lipo may be related to an increase in the cerebral monoamine concentrations.

  18. Antidepressant-like activity of sildenafil following acute and subchronic treatment in the forced swim test in mice: effects of restraint stress and monoamine depletion.

    PubMed

    Socała, Katarzyna; Nieoczym, Dorota; Pieróg, Mateusz; Szuster-Ciesielska, Agnieszka; Wyska, Elżbieta; Wlaź, Piotr

    2016-10-01

    Sildenafil is a highly effective oral agent for the treatment of erectile dysfunction of multiple etiologies. Although in clinical practice sildenafil is often used in depressed patients, its influence on the pathophysiology of depression remains unclear. The aim of the present study was to evaluate the antidepressant-like activity following acute and subchronic treatment with sildenafil in naïve mice as well as in mice with reserpine- and restraint stress-induced depressive-like behavior. Since corticosterone is released in response to acute stress, we also aimed to assess the influence of sildenafil on serum corticosterone level in non-stressed and stressed animals. The antidepressant activity of sildenafil was assessed in the forced swim test. Corticosterone serum level was determined by using ELISA method, while brain and serum sildenafil level via HPLC method. Sildenafil administered acutely exerted an antidepressant-like effect. Subchronic (14 days) administration of sildenafil resulted only in a weak antidepressant-like effect when evaluated 24 h after the last dose. Acute but not subchronic sildenafil administration reversed the reserpine- and stress-induced immobility in the forced swim test. The lack of effects of sildenafil after subchronic treatment could have been related to its complete elimination from the brain within 24 h from the last injection. Interestingly, acute administration of sildenafil produced a marked increase in serum corticosterone level in both non-stressed and stressed animals. Sildenafil exerts differential effects in the forced swim test after acute and subchronic administration. Further studies on the antidepressant activity of sildenafil are required.

  19. Role of 5-HT(1A) and 5-HT(1B) receptors in the antidepressant-like effect of piperine in the forced swim test.

    PubMed

    Mao, Qing-Qiu; Huang, Zhen; Ip, Siu-Po; Xian, Yan-Fang; Che, Chun-Tao

    2011-10-24

    Our previous studies have showed that treating mice with piperine significantly decreased the immobility time of the animals in the forced swim test and tail suspension test, which was related to up-regulation of serotonin (5-HT) level in the brain. The purpose of this study is to explore the contribution of 5-HT receptors in the antidepressant-like effect of piperine. The results showed that pre-treating mice with methiothepin (a non-selective 5-HT receptor antagonist, 0.1mg/kg, intraperitoneally), 4-(2'-methoxy-phenyl)-1-[2'-(n-2″-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (a selective 5-HT(1A) receptor antagonist, 1mg/kg, subcutaneously) or 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol (a 5-HT(1B) receptor antagonist, 2.5mg/kg, intraperitoneally) was found to abolish the anti-immobility effect of piperine (10mg/kg, intraperitoneally) in the forced swim test. On the other hand, a sub-effective dose of piperine (1mg/kg, intraperitoneally) produced a synergistic antidepressant-like effect with (+)-8-hydroxy-2-(di-n-propylamino)tetralin (a 5-HT(1A) receptor agonist, 1mg/kg, intraperitoneally) or anpirtoline (a 5-HT(1B) receptor agonist, 0.25mg/kg, intraperitoneally). Taken together, these results suggest that the antidepressant-like effect of piperine in the mouse forced swim test may be mediated, at least in part, by the activation of 5-HT(1A) and 5-HT(1B) receptors.

  20. Depressive behavior in the forced swim test can be induced by TRPV1 receptor activity and is dependent on NMDA receptors.

    PubMed

    Abdelhamid, Ramy E; Kovács, Katalin J; Nunez, Myra G; Larson, Alice A

    2014-01-01

    Blocking, desensitizing, or knocking out transient receptor potential vanilloid type 1 (TRPV1) receptors decreases immobility in the forced swim test, a measure of depressive behavior. We questioned whether enhancing TRPV1 activity promotes immobility in a fashion that is prevented by antidepressants. To test this we activated heat-sensitive TRPV1 receptors in mice by water that is warmer than body temperature (41 °C) or a low dose of resiniferatoxin (RTX). Water at 41 °C elicited less immobility than cooler water (26 °C), indicating that thermoregulatory sites do not contribute to immobility. Although a desensitizing regimen of RTX (3-5 injections of 0.1 mg/kg s.c.) decreased immobility during swims at 26 °C, it did not during swims at 41 °C. In contrast, low dose of RTX (0.02 mg/kg s.c.) enhanced immobility, but only during swims at 41 °C. Thus, activation of TRPV1 receptors, endogenously or exogenously, enhances immobility and these sites are activated by cold rather than warmth. Two distinct types of antidepressants, amitriptyline (10mg/kg i.p.) and ketamine (50 mg/kg i.p.), each inhibited the increase in immobility induced by the low dose of RTX, verifying its mediation by TRPV1 sites. When desensitization was limited to central populations using intrathecal injections of RTX (0.25 μg/kg i.t.), immobility was attenuated at both temperatures and the increase in immobility produced by the low dose of RTX was inhibited. This demonstrates a role for central TRPV1 receptors in depressive behavior, activated by conditions (cold stress) distinct from those that activate TRPV1 receptors along thermosensory afferents (heat). PMID:24200896

  1. Depressive behavior in the forced swim test can be induced by TRPV1 receptor activity and is dependent on NMDA receptors.

    PubMed

    Abdelhamid, Ramy E; Kovács, Katalin J; Nunez, Myra G; Larson, Alice A

    2014-01-01

    Blocking, desensitizing, or knocking out transient receptor potential vanilloid type 1 (TRPV1) receptors decreases immobility in the forced swim test, a measure of depressive behavior. We questioned whether enhancing TRPV1 activity promotes immobility in a fashion that is prevented by antidepressants. To test this we activated heat-sensitive TRPV1 receptors in mice by water that is warmer than body temperature (41 °C) or a low dose of resiniferatoxin (RTX). Water at 41 °C elicited less immobility than cooler water (26 °C), indicating that thermoregulatory sites do not contribute to immobility. Although a desensitizing regimen of RTX (3-5 injections of 0.1 mg/kg s.c.) decreased immobility during swims at 26 °C, it did not during swims at 41 °C. In contrast, low dose of RTX (0.02 mg/kg s.c.) enhanced immobility, but only during swims at 41 °C. Thus, activation of TRPV1 receptors, endogenously or exogenously, enhances immobility and these sites are activated by cold rather than warmth. Two distinct types of antidepressants, amitriptyline (10mg/kg i.p.) and ketamine (50 mg/kg i.p.), each inhibited the increase in immobility induced by the low dose of RTX, verifying its mediation by TRPV1 sites. When desensitization was limited to central populations using intrathecal injections of RTX (0.25 μg/kg i.t.), immobility was attenuated at both temperatures and the increase in immobility produced by the low dose of RTX was inhibited. This demonstrates a role for central TRPV1 receptors in depressive behavior, activated by conditions (cold stress) distinct from those that activate TRPV1 receptors along thermosensory afferents (heat).

  2. Involvement of adrenergic and serotonergic receptors in antidepressant-like effect of urocortin 3 in a modified forced swimming test in mice.

    PubMed

    Tanaka, Masaru; Telegdy, Gyula

    2008-11-25

    Most of the evidence suggests that peptides in the corticotropin-releasing factor (CRF) family act on CRF receptors and are involved in depressive disorders. Urocortin 3 (Ucn 3) is specific for CRF type 2 (CRF(2)) receptors and mediates anxiolytic-like action. Little is known about the roles of Ucn 3 and CRH(2) receptors on depressive disorders. The previous study revealed that Ucn 3 elicits the antidepressant-like action by shortening the immobility time and increasing both the climbing time and the swimming time. The involvement of the adrenergic and serotonergic receptors in the antidepressant-like effect of Ucn 3 (0.5μg/2μl, i.c.v.) was studied in a modified forced swimming test (FST) in mice. Mice were pretreated with a non-selective α-adrenergic receptor antagonist, phenoxybenzamine, an α(1)/α(2β)-adrenergic receptor antagonist, prazosin, an α(2)-adrenergic receptor antagonist, yohimbine, a mixed 5-HT(1)/5-HT(2) serotonergic receptor antagonist, methysergide, a non-selective 5-HT(2) serotonergic receptor antagonist, cyproheptadine or a β-adrenergic receptor antagonist, propranolol. Phenoxybenzamine prevented the effects of Ucn 3 on the immobility time. Prazosin prevented the effects of Ucn 3 on the climbing time. Yohimbine prevented the effects of Ucn 3 on the immobility, climbing and swimming times. Methysergide prevented the effects of Ucn 3 on the immobility and climbing time. Cyproheptadine prevented the effects of Ucn 3 on the swimming time. Propranolol did not change the effects of Ucn 3. The results demonstrated that the antidepressant-like effect of Ucn 3 is mediated, at least in part, by an interaction of the α-adrenergic and serotonergic receptors in a modified mouse FST.

  3. Antidepressant-like effects of the CRF family peptides, urocortin 1, urocortin 2 and urocortin 3 in a modified forced swimming test in mice.

    PubMed

    Tanaka, Masaru; Telegdy, Gyula

    2008-03-28

    Most of the evidence suggests that corticotropin-releasing hormone (CRH) is involved in mood disorders. The CRF receptors type 1 (CRF(1) receptors) elicit a stress response, and their natural and synthetic antagonists have been studied as possible drugs against depression, whereas CRF receptors type 2 (CRF(2) receptors) appear to alleviate the stress response and mediate anxiolytic action. Other CRF family peptides are urocortin 1 (Ucn 1), urocortin 2 (Ucn 2) and urocortin 3 (Ucn 3). Little is known about the action of Ucn 1, Ucn 2 and Ucn 3 on depressive disorders. Antidepressant-like effects of Ucn 1, Ucn 2 and Ucn 3 (0.13, 0.25 and 0.5 microg/2 microl, i.c.v.) were assayed in mice in a modified forced swimming test (FST). This modified FST predicts the clinical efficacy of an antidepressant drug through the scoring of immobility, climbing and swimming behavior. The study demonstrated that Ucn 1 had no action on any of parameters studied in the modified FST. Ucn 2 elicited antidepressive-like action by shortening the immobility time. Additionally Ucn 2 significantly increased the climbing and swimming times. Ucn 3 likewise displayed an antidepressive-like effect by shortening the immobility time, and increasing the climbing and swimming times. The results suggest that CRF(2) receptor stimulation by Ucn 2 or Ucn 3 leads to antidepressant-like action, but dual stimulation of the CRF(1) and CRF(2) receptors by Ucn 1 does not trigger antidepressant-like action in the modified mouse FST.

  4. Moderate swimming exercise and caffeine supplementation reduce the levels of inflammatory cytokines without causing oxidative stress in tissues of middle-aged rats.

    PubMed

    Cechella, José L; Leite, Marlon R; Dobrachinski, Fernando; da Rocha, Juliana T; Carvalho, Nelson R; Duarte, Marta M M F; Soares, Félix A A; Bresciani, Guilherme; Royes, Luiz F F; Zeni, Gilson

    2014-05-01

    The levels of circulatory inflammatory markers, including interleukin (IL) IL-1β, IL-6, tumor necrosis factor-α (TNF-α) and interferon (INF-γ), are known to increase associated to aging. Caffeine has been reported to produce many beneficial effects for health. Exercise is considered to be a safe medicine to attenuate inflammation and cellular senescence. The purpose of the present study was to investigate the effects of a moderate-intensity swimming exercise (3 % of body weight, 20 min per day, 4 weeks) and sub-chronic supplementation with caffeine (30 mg/kg, 4 weeks) on the serum cytokine levels in middle-aged (18 months) Wistar rats. The effects of swimming exercise and caffeine on oxidative stress in muscle and liver of middle-aged rats were also investigated. The two-way ANOVA of pro-inflammatory cytokine levels demonstrated a significant exercise x caffeine interaction for IL-1β (F (1, 16) = 9.5772; p = 0.0069), IL-6 (F (1, 16) = 8.0463; p = 0.0119) and INF-γ (F (1, 16) = 15.078; p = 0.0013). The two-way ANOVA of TNF-α levels revealed a significant exercise × caffeine interaction (F (1, 16) = 9.6881; p = 0.00670). Swimming exercise and caffeine supplementation increased the ratio of reduced glutathione/oxidized glutathione in the rat liver and gastrocnemius muscle. Hepatic and renal markers of damage were not modified. In conclusion, a moderate-intensity swimming exercise protocol and caffeine supplementation induced positive adaptations in modulating cytokine levels without causing oxidative stress in muscle and liver of middle-aged rats. PMID:24481487

  5. A diphenyl diselenide-supplemented diet and swimming exercise promote neuroprotection, reduced cell apoptosis and glial cell activation in the hypothalamus of old rats.

    PubMed

    Leite, Marlon R; Cechella, José L; Pinton, Simone; Nogueira, Cristina W; Zeni, Gilson

    2016-09-01

    Aging is a process characterized by deterioration of the homeostasis of various physiological systems; although being a process under influence of multiple factors, the mechanisms involved in aging are not well understood. Here we investigated the effect of a (PhSe)2-supplemented diet (1ppm, 4weeks) and swimming exercise (1% of body weight, 20min per day, 4weeks) on proteins related to glial cells activation, apoptosis and neuroprotection in the hypothalamus of old male Wistar rats (27month-old). Old rats had activation of astrocytes and microglia which was demonstrated by the increase in the levels of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba-1) in hypothalamus. A decrease of B-cell lymphoma 2 (Bcl-2) and procaspase-3 levels as well as an increase of the cleaved PARP/full length PARP ratio (poly (ADP-ribose) polymerase, PARP) and the pJNK/JNK ratio (c-Jun N-terminal kinase, JNK) were observed. The levels of mature brain-derived neurotrophic factor (mBDNF), the pAkt/Akt ratio (also known as protein kinase B) and NeuN (neuronal nuclei), a neuron marker, were decreased in the hypothalamus of old rats. Old rats that received a (PhSe)2-supplemented diet and performed swimming exercise had the hypothalamic levels of Iba-1 and GFAP decreased. The combined treatment also increased the levels of Bcl-2 and procaspase-3 and decreased the ratios of cleaved PARP/full length PARP and pJNK/JNK in old rats. The levels of mBDNF and NeuN, but not the pAkt/Akt ratio, were increased by combined treatment. In conclusion, a (PhSe)2-supplemented diet and swimming exercise promoted neuroprotection in the hypothalamus of old rats, reducing apoptosis and glial cell activation.

  6. A diphenyl diselenide-supplemented diet and swimming exercise promote neuroprotection, reduced cell apoptosis and glial cell activation in the hypothalamus of old rats.

    PubMed

    Leite, Marlon R; Cechella, José L; Pinton, Simone; Nogueira, Cristina W; Zeni, Gilson

    2016-09-01

    Aging is a process characterized by deterioration of the homeostasis of various physiological systems; although being a process under influence of multiple factors, the mechanisms involved in aging are not well understood. Here we investigated the effect of a (PhSe)2-supplemented diet (1ppm, 4weeks) and swimming exercise (1% of body weight, 20min per day, 4weeks) on proteins related to glial cells activation, apoptosis and neuroprotection in the hypothalamus of old male Wistar rats (27month-old). Old rats had activation of astrocytes and microglia which was demonstrated by the increase in the levels of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba-1) in hypothalamus. A decrease of B-cell lymphoma 2 (Bcl-2) and procaspase-3 levels as well as an increase of the cleaved PARP/full length PARP ratio (poly (ADP-ribose) polymerase, PARP) and the pJNK/JNK ratio (c-Jun N-terminal kinase, JNK) were observed. The levels of mature brain-derived neurotrophic factor (mBDNF), the pAkt/Akt ratio (also known as protein kinase B) and NeuN (neuronal nuclei), a neuron marker, were decreased in the hypothalamus of old rats. Old rats that received a (PhSe)2-supplemented diet and performed swimming exercise had the hypothalamic levels of Iba-1 and GFAP decreased. The combined treatment also increased the levels of Bcl-2 and procaspase-3 and decreased the ratios of cleaved PARP/full length PARP and pJNK/JNK in old rats. The levels of mBDNF and NeuN, but not the pAkt/Akt ratio, were increased by combined treatment. In conclusion, a (PhSe)2-supplemented diet and swimming exercise promoted neuroprotection in the hypothalamus of old rats, reducing apoptosis and glial cell activation. PMID:27215802

  7. Mouse strain differences in immobility and sensitivity to fluvoxamine and desipramine in the forced swimming test: analysis of serotonin and noradrenaline transporter binding.

    PubMed

    Sugimoto, Yumi; Kajiwara, Yoshinobu; Hirano, Kazufumi; Yamada, Shizuo; Tagawa, Noriko; Kobayashi, Yoshiharu; Hotta, Yoshihiro; Yamada, Jun

    2008-09-11

    Strain differences in immobility time in the forced swimming test were investigated in five strains of mice, namely, ICR, ddY, C57BL/6, DBA/2 and BALB/c mice. There were significant strain differences. The immobility times of ICR, ddY and C57BL/6 mice were longer than those of DBA/2 and BALB/c mice. Immobility times were not significantly related to locomotor activity in these strains. There were also differences in sensitivity to the selective serotonin reuptake inhibitor (SSRI) fluvoxamine. In ICR, ddY and C57BL/6 mice, fluvoxamine did not affect immobility time, while it reduced the immobility time of DBA/2 and BALB/c mice dose-dependently. The noradrenaline reuptake inhibitor desipramine decreased immobility time in all strains of mice. Serotonin (5-HT) transporter binding in the brains of all five strains of mice was also investigated. Analysis of 5-HT transporter binding revealed significant strain differences, being lower in DBA/2 and BALB/c mice than in other strains of mice. The amount of 5-HT transporter binding was correlated to baseline immobility time. However, there was no significant relation between noradrenaline transporter binding and immobility time. These results suggest that the duration of baseline immobility depends on the levels of 5-HT transporter binding, leading to apparent strain differences in immobility time in the forced swimming test. Furthermore, differences in 5-HT transporter binding may cause variations in responses to fluvoxamine.

  8. Both increases in immature dentate neuron number and decreases of immobility time in the forced swim test occurred in parallel after environmental enrichment of mice.

    PubMed

    Llorens-Martín, M V; Rueda, N; Martínez-Cué, C; Torres-Alemán, I; Flórez, J; Trejo, J L

    2007-07-13

    A direct relation between the rate of adult hippocampal neurogenesis in mice and the immobility time in a forced swim test after living in an enriched environment has been suggested previously. In the present work, young adult mice living in an enriched environment for 2 months developed considerably more immature differentiating neurons (doublecortin-positive, DCX(+)) than control, non-enriched animals. Furthermore, we found that the more DCX(+) cells they possessed, the lower the immobility time they scored in the forced swim test. This DCX(+) subpopulation is composed of mostly differentiating dentate neurons independently of the birthdates of every individual cell. However, variations found in this subpopulation were not the result of a general effect on the survival of any newborn neuron in the granule cell layer, as 5-bromo-2-deoxyuridine (BrdU)-labeled cells born during a narrow time window included in the longer lifetime period of DCX(+) cells, were not significantly modified after enrichment. In contrast, the survival of the mature population of neurons in the granule cell layer of the dentate gyrus in enriched animals increased, although this did not influence their performance in the Porsolt test, nor did it influence the dentate gyrus volume or granule neuronal nuclei size. These results indicate that the population of immature, differentiating neurons in the adult hippocampus is one factor directly related to the protective effect of an enriched environment against a highly stressful event.

  9. Association between gravitational force and tissue metabolism in periparturient rats

    NASA Technical Reports Server (NTRS)

    Zakrzewska, E. I.; Maple, R.; Lintault, L.; Wade, C.; Baer, L.; Ronca, A.; Plaut, K.

    2004-01-01

    Recently, interest in mammalian reproduction and offspring survival in altered gravity has been growing. Because successful lactation is critical for mammalian neonate survival, we have been studying the effect of gravity metabolism. We have shown an exponential relationship between glucose metabolic rate in mammary tissue of periparturient rats and an increase in gravity load. In this study we showed that changes in mammary metabolic rate due to gravity force were accompanied by a decrease in glucose metabolism in adipose tissue and by a reduced size of adipocytes. We assume that these changes are likely due to changes in prolactin or leptin levels related to altered gravity load.

  10. Chronic flumazenil (Ro 15-1788) facilitates acquisition and retention of a swim-escape response in rats.

    PubMed

    Urbancic, M; Gadek, M; Marczynski, T J

    Since chronic flumazenil treatment was previously found to stimulate exploratory behavior in rodents, the aim of this study was to test the effect of chronic exposure to flumazenil on acquisition and retention of escape behavior. Adult rats were treated with flumazenil (Ro 15-1788; 4 mg/kg/day in drinking water) for 21 days (experiment 1) and for 17 days (experiment 2). In experiment 1 (a round water tank with one escape rope) conducted 24 h after drug/vehicle withdrawal, the time the animals needed to resolve a swim-escape task was significantly shorter in the drug group, compared to the controls. In the retention trial, 24 h later, the control group matched the performance of the drug group. In experiment 2, a water T-maze was used which was equipped with two ropes, one anchored to the bottom and the other unanchored and therefore was more difficult to climb. On day 14 of flumazenil/vehicle treatment, there were no differences between the groups in the time needed to escape from the maze. However, on day 15 and 16 of drug/vehicle treatment, the drug group made highly significant progress, while the control group showed no improvement of the escape behavior. The possible mechanisms of flumazenil-induced facilitation of escape behavior have been discussed.

  11. Secondary Structure of Rat and Human Amylin across Force Fields.

    PubMed

    Hoffmann, Kyle Quynn; McGovern, Michael; Chiu, Chi-Cheng; de Pablo, Juan J

    2015-01-01

    The aggregation of human amylin has been strongly implicated in the progression of Type II diabetes. This 37-residue peptide forms a variety of secondary structures, including random coils, α-helices, and β-hairpins. The balance between these structures depends on the chemical environment, making amylin an ideal candidate to examine inherent biases in force fields. Rat amylin differs from human amylin by only 6 residues; however, it does not form fibrils. Therefore it provides a useful complement to human amylin in studies of the key events along the aggregation pathway. In this work, the free energy of rat and human amylin was determined as a function of α-helix and β-hairpin content for the Gromos96 53a6, OPLS-AA/L, CHARMM22/CMAP, CHARMM22*, Amberff99sb*-ILDN, and Amberff03w force fields using advanced sampling techniques, specifically bias exchange metadynamics. This work represents a first systematic attempt to evaluate the conformations and the corresponding free energy of a large, clinically relevant disordered peptide in solution across force fields. The NMR chemical shifts of rIAPP were calculated for each of the force fields using their respective free energy maps, allowing us to quantitatively assess their predictions. We show that the predicted distribution of secondary structures is sensitive to the choice of force-field: Gromos53a6 is biased towards β-hairpins, while CHARMM22/CMAP predicts structures that are overly α-helical. OPLS-AA/L favors disordered structures. Amberff99sb*-ILDN, AmberFF03w and CHARMM22* provide the balance between secondary structures that is most consistent with available experimental data. In contrast to previous reports, our findings suggest that the equilibrium conformations of human and rat amylin are remarkably similar, but that subtle differences arise in transient alpha-helical and beta-strand containing structures that the human peptide can more readily adopt. We hypothesize that these transient states enable

  12. Secondary Structure of Rat and Human Amylin across Force Fields.

    PubMed

    Hoffmann, Kyle Quynn; McGovern, Michael; Chiu, Chi-Cheng; de Pablo, Juan J

    2015-01-01

    The aggregation of human amylin has been strongly implicated in the progression of Type II diabetes. This 37-residue peptide forms a variety of secondary structures, including random coils, α-helices, and β-hairpins. The balance between these structures depends on the chemical environment, making amylin an ideal candidate to examine inherent biases in force fields. Rat amylin differs from human amylin by only 6 residues; however, it does not form fibrils. Therefore it provides a useful complement to human amylin in studies of the key events along the aggregation pathway. In this work, the free energy of rat and human amylin was determined as a function of α-helix and β-hairpin content for the Gromos96 53a6, OPLS-AA/L, CHARMM22/CMAP, CHARMM22*, Amberff99sb*-ILDN, and Amberff03w force fields using advanced sampling techniques, specifically bias exchange metadynamics. This work represents a first systematic attempt to evaluate the conformations and the corresponding free energy of a large, clinically relevant disordered peptide in solution across force fields. The NMR chemical shifts of rIAPP were calculated for each of the force fields using their respective free energy maps, allowing us to quantitatively assess their predictions. We show that the predicted distribution of secondary structures is sensitive to the choice of force-field: Gromos53a6 is biased towards β-hairpins, while CHARMM22/CMAP predicts structures that are overly α-helical. OPLS-AA/L favors disordered structures. Amberff99sb*-ILDN, AmberFF03w and CHARMM22* provide the balance between secondary structures that is most consistent with available experimental data. In contrast to previous reports, our findings suggest that the equilibrium conformations of human and rat amylin are remarkably similar, but that subtle differences arise in transient alpha-helical and beta-strand containing structures that the human peptide can more readily adopt. We hypothesize that these transient states enable

  13. Secondary Structure of Rat and Human Amylin across Force Fields

    PubMed Central

    Hoffmann, Kyle Quynn; McGovern, Michael; Chiu, Chi-cheng; de Pablo, Juan J.

    2015-01-01

    The aggregation of human amylin has been strongly implicated in the progression of Type II diabetes. This 37-residue peptide forms a variety of secondary structures, including random coils, α-helices, and β-hairpins. The balance between these structures depends on the chemical environment, making amylin an ideal candidate to examine inherent biases in force fields. Rat amylin differs from human amylin by only 6 residues; however, it does not form fibrils. Therefore it provides a useful complement to human amylin in studies of the key events along the aggregation pathway. In this work, the free energy of rat and human amylin was determined as a function of α-helix and β-hairpin content for the Gromos96 53a6, OPLS-AA/L, CHARMM22/CMAP, CHARMM22*, Amberff99sb*-ILDN, and Amberff03w force fields using advanced sampling techniques, specifically bias exchange metadynamics. This work represents a first systematic attempt to evaluate the conformations and the corresponding free energy of a large, clinically relevant disordered peptide in solution across force fields. The NMR chemical shifts of rIAPP were calculated for each of the force fields using their respective free energy maps, allowing us to quantitatively assess their predictions. We show that the predicted distribution of secondary structures is sensitive to the choice of force-field: Gromos53a6 is biased towards β-hairpins, while CHARMM22/CMAP predicts structures that are overly α-helical. OPLS-AA/L favors disordered structures. Amberff99sb*-ILDN, AmberFF03w and CHARMM22* provide the balance between secondary structures that is most consistent with available experimental data. In contrast to previous reports, our findings suggest that the equilibrium conformations of human and rat amylin are remarkably similar, but that subtle differences arise in transient alpha-helical and beta-strand containing structures that the human peptide can more readily adopt. We hypothesize that these transient states enable

  14. Secondary structure of rat and human amylin across force fields

    DOE PAGESBeta

    Hoffmann, Kyle Quynn; McGovern, Michael; Chiu, Chi -cheng; de Pablo, Juan J.; Paci, Emanuele

    2015-07-29

    The aggregation of human amylin has been strongly implicated in the progression of Type II diabetes. This 37-residue peptide forms a variety of secondary structures, including random coils, α-helices, and β-hairpins. The balance between these structures depends on the chemical environment, making amylin an ideal candidate to examine inherent biases in force fields. Rat amylin differs from human amylin by only 6 residues; however, it does not form fibrils. Therefore it provides a useful complement to human amylin in studies of the key events along the aggregation pathway. In this work, the free energy of rat and human amylin wasmore » determined as a function of α-helix and β-hairpin content for the Gromos96 53a6, OPLS-AA/L, CHARMM22/CMAP, CHARMM22*, Amberff99sb*-ILDN, and Amberff03w force fields using advanced sampling techniques, specifically bias exchange metadynamics. This work represents a first systematic attempt to evaluate the conformations and the corresponding free energy of a large, clinically relevant disordered peptide in solution across force fields. The NMR chemical shifts of rIAPP were calculated for each of the force fields using their respective free energy maps, allowing us to quantitatively assess their predictions. We show that the predicted distribution of secondary structures is sensitive to the choice of force-field: Gromos53a6 is biased towards β-hairpins, while CHARMM22/CMAP predicts structures that are overly α-helical. OPLS-AA/L favors disordered structures. Amberff99sb*-ILDN, AmberFF03w and CHARMM22* provide the balance between secondary structures that is most consistent with available experimental data. In contrast to previous reports, our findings suggest that the equilibrium conformations of human and rat amylin are remarkably similar, but that subtle differences arise in transient alpha-helical and beta-strand containing structures that the human peptide can more readily adopt. We hypothesize that these transient states

  15. Secondary structure of rat and human amylin across force fields

    SciTech Connect

    Hoffmann, Kyle Quynn; McGovern, Michael; Chiu, Chi -cheng; de Pablo, Juan J.; Paci, Emanuele

    2015-07-29

    The aggregation of human amylin has been strongly implicated in the progression of Type II diabetes. This 37-residue peptide forms a variety of secondary structures, including random coils, α-helices, and β-hairpins. The balance between these structures depends on the chemical environment, making amylin an ideal candidate to examine inherent biases in force fields. Rat amylin differs from human amylin by only 6 residues; however, it does not form fibrils. Therefore it provides a useful complement to human amylin in studies of the key events along the aggregation pathway. In this work, the free energy of rat and human amylin was determined as a function of α-helix and β-hairpin content for the Gromos96 53a6, OPLS-AA/L, CHARMM22/CMAP, CHARMM22*, Amberff99sb*-ILDN, and Amberff03w force fields using advanced sampling techniques, specifically bias exchange metadynamics. This work represents a first systematic attempt to evaluate the conformations and the corresponding free energy of a large, clinically relevant disordered peptide in solution across force fields. The NMR chemical shifts of rIAPP were calculated for each of the force fields using their respective free energy maps, allowing us to quantitatively assess their predictions. We show that the predicted distribution of secondary structures is sensitive to the choice of force-field: Gromos53a6 is biased towards β-hairpins, while CHARMM22/CMAP predicts structures that are overly α-helical. OPLS-AA/L favors disordered structures. Amberff99sb*-ILDN, AmberFF03w and CHARMM22* provide the balance between secondary structures that is most consistent with available experimental data. In contrast to previous reports, our findings suggest that the equilibrium conformations of human and rat amylin are remarkably similar, but that subtle differences arise in transient alpha-helical and beta-strand containing structures that the human peptide can more readily adopt. We hypothesize that these transient states enable

  16. The relationship between anxiety and depression in animal models: a study using the forced swimming test and elevated plus-maze.

    PubMed

    Andreatini, R; Bacellar, L F

    1999-09-01

    The present study evaluated the correlation between the behavior of mice in the forced swimming test (FST) and in the elevated plus-maze (PM). The effect of the order of the experiments, i.e., the influence of the first test (FST or PM) on mouse behavior in the second test (PM or FST, respectively) was compared to handled animals (HAND). The execution of FST one week before the plus-maze (FST-PM, N = 10), in comparison to mice that were only handled (HAND-PM, N = 10) in week 1, decreased % open entries (HAND-PM: 33.6 +/- 2.9; FST-PM: 20.0 +/- 3.9; mean +/- SEM; P<0.02) and % open time (HAND-PM: 18.9 +/- 3.3; FST-PM: 9.0 +/- 1.9; P<0.03), suggesting an anxiogenic effect. No significant effect was seen in the number of closed arm entries (FST-PM: 9.5 (7.0-11.0); HAND-PM: 10.0 (4.0-14.5), median (interquartile range); U = 46.5; P>0.10). A prior test in the plus-maze (PM-FST) did not change % immobility time in the FST when compared to the HAND-FST group (HAND-FST: 57.7 +/- 3.9; PM-FST: 65.7 +/- 3.2; mean +/- SEM; P>0.10). Since these data suggest that there is an order effect, the correlation was evaluated separately with each test sequence: FST-PM (N = 20) and PM-FST (N = 18). There was no significant correlation between % immobility time in the FST and plus-maze indexes (% time and entries in open arms) in any test sequence (r: -0.07 to 0.18). These data suggest that mouse behavior in the elevated plus-maze is not related to behavior in the forced swimming test and that a forced swimming test before the plus-maze has an anxiogenic effect even after a one-week interval.

  17. Pindolol does not act only on 5-HT1A receptors in augmenting antidepressant activity in the mouse forced swimming test.

    PubMed

    Bourin, M; Redrobe, J P; Baker, G B

    1998-04-01

    The present study was undertaken to identify the receptor subtypes involved in (+/-) pindolol's ability to enhance the effects of antidepressant drugs in the mouse forced swimming test. Interaction studies were performed with S 15535 (presynaptic 5-HT1A receptor agonist) and methiothepin (5-HT1B autoreceptor antagonist) in an attempt to attenuate or potentiate antidepressant-like activity. (+/-) Pindolol was tested in combination with selective agonists and antagonists at 5-HT1, 5-HT2 and 5-HT3 receptor subtypes. Pretreatment with S 15535 and methiothepin attenuated the activity of paroxetine, fluvoxamine and citalopram (32 mg/kg, i.p.; P < 0.01). (+/-) Pindolol (32 mg/kg, i.p.) induced significant anti-immobility effects when tested in combination with 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU 24969) (1 mg/kg, i.p.; P < 0.05), 1-(2-methoxyphenyl)-4-[-(2-phthalimido) butyl]piperazine) (NAN 190) (0.5 mg/kg; P < 0.05) and ondansetron (0.00001 mg/kg, i.p.; P < 0.01). Pretreatment with NAN 190 (0.5 mg/kg, i.p.) potentiated the effects of RU 24969 (1 mg/kg, i.p.; P < 0.05) and (+/-) pindolol (32 mg/kg, i.p.; P < 0.05) in the forced swimming test, as did ondansetron (0.00001 mg/kg, i.p.). Significant additive effects were induced when RU 24969 (1 mg/kg, i.p.) was tested in combination with NAN 190 (0.5 mg/kg, i.p.; P < 0.05), (+/-) pindolol (32 mg/kg, i.p.; P < 0.05) and ondansetron (0.0000 mg/kg, i.p.; P < 0.05). 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1 mg/kg, i.p.) or ketanserin (8 mg/kg, i.p.) did not induce significant antidepressant-like effects with any of the agonists/antagonists tested. The results of the present study suggest that pindolol is acting at presynaptic 5-HT1B serotonergic receptors, in addition to the 5-HT1A subtype, in augmenting the activity of antidepressants in the mouse forced swimming test.

  18. Test-retest paradigm of the forced swimming test in female mice is not valid for predicting antidepressant-like activity: participation of acetylcholine and sigma-1 receptors.

    PubMed

    Su, Jing; Hato-Yamada, Noriko; Araki, Hiroaki; Yoshimura, Hiroyuki

    2013-01-01

    The forced swimming test (FST) in mice is widely used to predict the antidepressant activity of a drug, but information describing the immobility of female mice is limited. We investigated whether a prior swimming experience affects the immobility duration in a second FST in female mice and whether the test-retest paradigm is a valid screening tool for antidepressants. Female ICR mice were exposed to the FST using two experimental paradigms: a single FST and a double FST in which mice had experienced FST once 24 h prior to the second trail. The initial FST experience reliably prolonged immobility duration in the second FST. The antidepressants imipramine and paroxetine significantly reduced immobility duration in the single FST, but not in the double FST. Scopolamine and the sigma-1 (σ1) antagonist NE-100 administered before the second trial significantly prevented the prolongation of immobility. Neither a 5-HT1A nor a 5-HT2A receptor agonist affected immobility duration. We suggest that the test-retest paradigm in female mice is not adequate for predicting antidepressant-like activity of a drug; the prolongation of immobility in the double FST is modulated through acetylcholine and σ1 receptors.

  19. Relationships between blood Mg2+ and energy metabolites/enzymes after acute exhaustive swimming exercise in rats.

    PubMed

    Rahman, Md Mahbubur; Lee, Sei-Jin; Mun, A-Reum; Adam, Gareeballah Osman; Park, Ra-Mi; Kim, Gi-Beum; Kang, Hyung-Sub; Kim, Jin-Shang; Kim, Shang-Jin; Kim, Sung-Zoo

    2014-10-01

    Magnesium (Mg) plays a central role in neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, and blood pressure, all of which are significantly related to physical performance. To date, the available data about detection of blood total Mg (tMg; free-ionized, protein-bound, and anion-complex forms) are inconsistent, and there is limited information on blood free-ionized Mg (Mg(2+)) in relation to physical exercise. The aim of this study was to determine the biochemical changes related to energy metabolism after acute exhaustive swimming exercise (AESE) in rats in an attempt to correlate the role of blood Mg(2+) with metabolites/enzymes related to energy production. After AESE, blood Mg(2+), tMg, K(+), partial pressure of carbon dioxide, lactate, total protein (T-PRO), high-density lipoprotein (HDL), creatinine (CRE), blood urea nitrogen (BUN), uric acid (UA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alanine phosphatase (ALP), lactate dehydrogenase (LDH), and creatinine kinase (CK) were significantly increased, whereas pH, partial pressure of oxygen, oxygen saturation, the Mg(2+)/tMg and Ca(2+)/Mg(2+) ratios, HCO3 (-), glucose, triglyceride (TG), and low-density lipoprotein (LDL) were significantly decreased. During AESE, lactate, T-PRO, albumin, AST, ALP, LDH, CK, CRE, BUN, and UA showed significant positive correlations with changes in blood Mg(2+), while glucose, TG, and LDL correlated to Mg(2+) in a negative manner. In conclusion, AESE induced increases in both blood Mg(2+) and tMg, accompanied by changes in blood metabolites and enzymes related to energy metabolism due to increased metabolic demands and mechanical damages.

  20. Evidence of the activity of lithium on 5-HT1B receptors in the mouse forced swimming test: comparison with carbamazepine and sodium valproate.

    PubMed

    Redrobe, J P; Bourin, M

    1999-02-01

    The use of lithium in combination with various antidepressant drugs (e.g., heterocyclics and monoamine oxidase inhibitors) has been reported rapidly to improve antidepressant response in otherwise treatment-resistant patients. Carbamazepine and sodium valproate have also been shown to be effective in the treatment of several forms of affective disorders, such as treatment-resistant depression and bipolar depression. The present study, using the mouse forced swimming test, was undertaken to test the hypothesis of the action of lithium, carbamazepine or sodium valproate on some 5-HT receptor subtypes. Results showed that lithium significantly potentiated the anti-immobility effects of RU 24969 (P<0.01) and anpirtoline (P<0.01). Pretreatment with lithium did not induce any significant antidepressant-like effects when tested in combination with 8-OH-DPAT, NAN-190 or (+/-) pindolol. Pretreatment with carbamazepine provoked anti-immobility effects when tested in combination with RU 24969 (P<0.01) and 8-OH-DPAT (P<0.01), whereas prior administration of sodium valproate enhanced the antidepressant-like effects of (+/-) pindolol (P<0.01), 8-OH-DPAT (P<0.01) and RU 24969 (P<0.01). In conclusion, the results of the present study suggest that lithium may be acting through 5-HT1B receptors, whereas the action of carbamazepine and sodium valproate seems to involve 5-HT1A receptors in the mouse forced swimming test. However, considering the complexity of the actions of these compounds, it is possible that other neurotransmitter systems/receptors may be involved.

  1. Partial role of 5-HT2 and 5-HT3 receptors in the activity of antidepressants in the mouse forced swimming test.

    PubMed

    Redrobe, J P; Bourin, M

    1997-05-01

    The present study was designed to evaluate the roles of 5-HT2 and 5-HT3 receptors in the mouse forced swimming test, by using selective agonists and antagonists of 5-HT(2A/C) and 5-HT3 receptor sites. Agonists/antagonists and antidepressants were administered 45 min and 30 min, respectively, prior to testing. Pretreatment with (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) (4 mg/kg, i.p.) or 2-methyl-5-HT (4 mg/kg, i.p.) had no effect on the anti-immobility effects of any antidepressant tested. Prior administration of ritanserin (4 mg/kg, i.p.) or ketanserin (8 mg/kg, i.p.), on the other hand, potentiated the effects of sub-active doses of imipramine (8 mg/kg, i.p.) and desipramine (16 mg/kg, i.p.) but not of maprotiline (8 mg/kg, i.p.), fluoxetine (16 mg/kg, i.p.), citalopram (16 mg/kg, i.p.) or fluvoxamine (8 mg/kg, i.p.). Pretreatment with ondansetron (1 X 10(-5) mg/kg, i.p.) enhanced the antidepressant-like effects of sub-active doses of the selective serotonin reuptake inhibitors. The results of the present study suggested that, in the forced swimming test, the selective serotonin reuptake inhibitors act partially through 5-HT3 receptor sites, whereas the tricyclic antidepressants exert effects at 5-HT(2A/C) receptor sites. Anti-immobility effects of the selective noradrenaline reuptake inhibitor, maprotiline, do not seem to be mediated by 5-HT(2A/C) or 5-HT3 receptor function.

  2. The involvement of NMDA receptor/NO/cGMP pathway in the antidepressant like effects of baclofen in mouse force swimming test.

    PubMed

    Khan, Muhammad Imran; Ostadhadi, Sattar; Zolfaghari, Samira; Ejtemaei Mehr, Shahram; Hassanzadeh, Gholamreza; Dehpour, Ahmad-Reza

    2016-01-26

    In the current study, the involvement of N-methyl-d-aspartate receptor (NMDAR) and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system in the antidepressant-like effects of baclofen was evaluated by using animal model in forced swimming test. Followed by an open field test for the evaluation of locomotor activity, the immobility time for mice in force swimming test was recorded. Only the last four min was analyzed. Administration of Baclofen (0.5 and 1mg/kg, i.p.) reduced the immobility interval in the FST. Prior administration of l-arginine (750mg/kg, i.p.,) a nitric oxide synthase substrate or sildenafil (5mg/kg, i.p.) a phosphodiesterase 5 into mice suppressed the antidepressant-like activity of baclofen (1mg/kg, i.p.).Co-treatment of 7-nitroindazole (50mg/kg, i.p.,) an inhibitor of neuronal nitric oxide synthase, L-NAME (10mg/kg, i.p.,) a non-specific inhibitor of nitric oxide synthase or MK-801 (0.05mg/kg, i.p.) an NMDA receptor antagonist with subeffective dose of baclofen (0.1mg/kg, i.p.), reduced the immobility time in the FST as compared to the drugs when used alone. Co-administrated of lower doses of MK-801 (0.01mg/kg) or l-NAME (1mg/kg) failed to effect immobility time however, simultaneous administration of these two agents in same dose with subeffective dose of baclofen (0.1mg/kg, i.p.), minimized the immobility time in the FST. Thus, our results support the role of NMDA receptors and l-arginine-NO-GMP pathway in the antidepressant-like action of baclofen. PMID:26679225

  3. Dopamine D2/D3 but not dopamine D1 receptors are involved in the rapid antidepressant-like effects of ketamine in the forced swim test.

    PubMed

    Li, Yan; Zhu, Zhuo R; Ou, Bao C; Wang, Ya Q; Tan, Zhou B; Deng, Chang M; Gao, Yi Y; Tang, Ming; So, Ji H; Mu, Yang L; Zhang, Lan Q

    2015-02-15

    Major depressive disorder is one of the most prevalent and life-threatening forms of mental illnesses. The traditional antidepressants often take several weeks, even months, to obtain clinical effects. However, recent clinical studies have shown that ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects within 2h and are long-lasting. The aim of the present study was to investigate whether dopaminergic system was involved in the rapid antidepressant effects of ketamine. The acute administration of ketamine (20 mg/kg) significantly reduced the immobility time in the forced swim test. MK-801 (0.1 mg/kg), the more selective NMDA antagonist, also exerted rapid antidepressant-like effects. In contrast, fluoxetine (10 mg/kg) did not significantly reduced the immobility time in the forced swim test after 30 min administration. Notably, pretreatment with haloperidol (0.15 mg/kg, a nonselective dopamine D2/D3 antagonist), but not SCH23390 (0.04 and 0.1 mg/kg, a selective dopamine D1 receptor antagonist), significantly prevented the effects of ketamine or MK-801. Moreover, the administration of sub-effective dose of ketamine (10 mg/kg) in combination with pramipexole (0.3 mg/kg, a dopamine D2/D3 receptor agonist) exerted antidepressant-like effects compared with each drug alone. In conclusion, our results indicated that the dopamine D2/D3 receptors, but not D1 receptors, are involved in the rapid antidepressant-like effects of ketamine.

  4. The involvement of NMDA receptor/NO/cGMP pathway in the antidepressant like effects of baclofen in mouse force swimming test.

    PubMed

    Khan, Muhammad Imran; Ostadhadi, Sattar; Zolfaghari, Samira; Ejtemaei Mehr, Shahram; Hassanzadeh, Gholamreza; Dehpour, Ahmad-Reza

    2016-01-26

    In the current study, the involvement of N-methyl-d-aspartate receptor (NMDAR) and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system in the antidepressant-like effects of baclofen was evaluated by using animal model in forced swimming test. Followed by an open field test for the evaluation of locomotor activity, the immobility time for mice in force swimming test was recorded. Only the last four min was analyzed. Administration of Baclofen (0.5 and 1mg/kg, i.p.) reduced the immobility interval in the FST. Prior administration of l-arginine (750mg/kg, i.p.,) a nitric oxide synthase substrate or sildenafil (5mg/kg, i.p.) a phosphodiesterase 5 into mice suppressed the antidepressant-like activity of baclofen (1mg/kg, i.p.).Co-treatment of 7-nitroindazole (50mg/kg, i.p.,) an inhibitor of neuronal nitric oxide synthase, L-NAME (10mg/kg, i.p.,) a non-specific inhibitor of nitric oxide synthase or MK-801 (0.05mg/kg, i.p.) an NMDA receptor antagonist with subeffective dose of baclofen (0.1mg/kg, i.p.), reduced the immobility time in the FST as compared to the drugs when used alone. Co-administrated of lower doses of MK-801 (0.01mg/kg) or l-NAME (1mg/kg) failed to effect immobility time however, simultaneous administration of these two agents in same dose with subeffective dose of baclofen (0.1mg/kg, i.p.), minimized the immobility time in the FST. Thus, our results support the role of NMDA receptors and l-arginine-NO-GMP pathway in the antidepressant-like action of baclofen.

  5. The neurosteroid dehydroepiandrosterone sulfate, but not androsterone, enhances the antidepressant effect of cocaine examined in the forced swim test--Possible role of serotonergic neurotransmission.

    PubMed

    Krzascik, Pawel; Zajda, Malgorzata Elzbieta; Majewska, Maria Dorota

    2015-04-01

    One of the mechanisms of cocaine's actions in the central nervous system is its antidepressant action. This effect might be responsible for increased usage of the drug by individuals with mood disorders. Higher endogenous levels of the excitatory neurosteroid dehydroepiandrosterone sulfate (DHEAS) were reported to correlate with successful abstinence from cocaine use in addicts, but a clinical trial showed that supplementation with a high dose of DHEA increased cocaine usage instead. Such ambiguous effects of DHEA(S) could potentially be linked to its influence on the antidepressant effect of cocaine. In this study we tested DHEAS and its metabolite, androsterone, for interactions with cocaine in animal model of depression (forced swim test) and examined the effects of both steroids and cocaine on serotoninergic neurotransmission. All substances were also tested for influence on locomotor activity. A cocaine dose of 5mg/kg, which had no significant effect on locomotor activity, was chosen for the forced swim test. Neither DHEAS nor androsterone showed any antidepressant action in this test, while cocaine manifested a clear antidepressant effect. Androsterone slightly reduced the antidepressant influence of cocaine while DHEAS markedly, dose-dependently enhanced it. Such an effect might be caused by the influence of DHEAS on serotonin neurotransmission, as this steroid decreased serotonin concentration and turnover in the striatum. When DHEAS and cocaine were administered together, the levels of serotonin in the striatum and hippocampus remained unchanged. This phenomenon may explain the additive antidepressant action of DHEAS and cocaine and why co-administration of DHEAS and cocaine increases drug use.

  6. The influence of the hand's acceleration and the relative contribution of drag and lift forces in front crawl swimming.

    PubMed

    Gourgoulis, Vassilios; Boli, Alexia; Aggeloussis, Nikolaos; Antoniou, Panagiotis; Toubekis, Argyris; Mavromatis, Georgios

    2015-01-01

    The aim of this study was to assess the effect of the hand's acceleration on the propulsive forces and the relative contribution of the drag and lift on their resultant force in the separate phases of the front crawl underwater arm stroke. Ten female swimmers swam one trial of all-out 25-m front crawl. The underwater motion of each swimmer's right hand was recorded using four camcorders and four periscope systems. Anatomical landmarks were digitised, and the propulsive forces generated by the swimmer's hand were estimated from the kinematic data in conjunction with hydrodynamic coefficients. When the hand's acceleration was taken into account, the magnitude of the propulsive forces was greater, with the exception of the mean drag force during the final part of the underwater arm stroke. The mean drag force was greater than the mean lift force in the middle part, while the mean lift force was greater than the mean drag force in the final part of the underwater arm stroke. Thus, swimmers should accelerate their hands from the beginning of their backward motion, press the water with large pitch angles during the middle part and sweep with small pitch angles during the final part of their underwater arm stroke.

  7. [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. PMID:26080600

  8. A lack of α1A-adrenergic receptor-mediated antidepressant-like effects of S-(+)-niguldipine and B8805-033 in the forced swim test.

    PubMed

    Kreiner, Grzegorz; Roman, Adam; Zelek-Molik, Agnieszka; Kowalska, Marta; Nalepa, Irena

    2016-06-01

    The α1-adrenergic receptors (α1-ARs), which belong to a G protein-coupled receptor family, consist of three highly homologous subtypes known as α1A-ARs, α1B-ARs, and α1D-ARs. Our previous findings suggested that α1A-ARs are an important target for imipramine and electroconvulsive therapy. The current study sought to evaluate whether S-(+)-niguldipine and B8805-033, two selective antagonists of α1A-ARs, can evoke antidepressant-like effects in the forced swim test in rats. Both compounds were administered at three time points (24, 5, and 1 h before testing), and the effects of three doses (2, 5, and 10 mg/kg) of each compound were investigated. S-(+)-Niguldipine produced no antidepressant-like effects other than a 14% reduction in immobility time at the highest dose. Although B8805-033 at a dose of 2 mg/kg did not influence the rats' behavior, higher B8805-033 doses (5 and 10 mg/kg) produced significant reductions in immobility time (approximately 42 and 44% vs. controls, respectively; P<0.01). However, this effect was abolished by the concomitant administration of WAY100135, a serotonin receptor antagonist, suggesting that the observed antidepressant-like effects of B8805-033 are unrelated to α1A-ARs. Nevertheless, given the current dearth of selective α1A-AR agonists, the question of whether this particular subtype could be involved in antidepressant therapy mechanisms remains unresolved.

  9. Opioid/NMDA receptors blockade reverses the depressant-like behavior of foot shock stress in the mouse forced swimming test.

    PubMed

    Haj-Mirzaian, Arya; Ostadhadi, Sattar; Kordjazy, Nastaran; Dehpour, Ahmad Reza; Ejtemaei Mehr, Shahram

    2014-07-15

    Opioid and glutamatergic receptors have a key role in depression following stress. In this study, we assessed opioid and glutamatergic receptors interaction with the depressant-like behavior of acute foot-shock stress in the mouse forced swimming test. Stress was induced by intermittent foot shock stimulation during 30min and swim periods were afterwards conducted by placing mice in separated glass cylinders filled with water for 6min. The immobility time during the last 4min of the test was considered. Acute foot-shock stress significantly increased the immobility time of mice compared to non-stressed control group (P≤0.01). Administration of non-selective opioid receptors antagonist, naltrexone (1 and 2mg/kg, i.p.), and the selective non-competitive NMDA receptor antagonist, MK-801 (0.05mg/kg, i.p.), and the selective serotonin reuptake inhibitor, fluoxetine (5mg/kg), significantly reduced the immobility time in stressed animals (P≤0.01). Lower doses of MK-801 (0.01mg/kg), naltrexone (0.3mg/kg), NMDA (75mg/kg) and morphine(5mg/kg) had no effect on foot-shock stressed mice. Combined treatment of sub-effective doses of naltrexone and MK-801 significantly showed an antidepressant-like effect (P≤0.001). On the other hand, co-administration of non-effective doses of NMDA and morphine with effective doses of naltrexone and MK-801 reversed the anti-immobility effect of these drugs. Taken together, we have for the first time demonstrated the possible role of opioid/NMDA receptors signaling in the depressant-like effect of foot-shock stress, and proposed the use of drugs that act like standard anti-depressants in stress-induced depression.

  10. Sildenafil, a phosphodiesterase type 5 inhibitor, enhances the antidepressant activity of amitriptyline but not desipramine, in the forced swim test in mice.

    PubMed

    Socała, Katarzyna; Nieoczym, Dorota; Wyska, Elżbieta; Poleszak, Ewa; Wlaź, Piotr

    2012-06-01

    The cholinergic theory of depression highlights the involvement of muscarinic acetylcholine receptors in the neurobiology of mood disorders. The present study was designed to investigate the effect of sildenafil, a phosphodiesterase type 5 inhibitor which exhibits cholinomimetic properties, alone and in combination with scopolamine in the forced swim test in mice. Moreover, we assessed the ability of sildenafil to modify the antidepressant activity of two tricyclic antidepressants with distinct cholinolytic activity, amitriptyline and desipramine. Swim sessions were conducted by placing mice in glass cylinders filled with water for 6 min and the duration of behavioral immobility during the last 4 min of the test was evaluated. Locomotor activity was measured with photoresistor actimeters. To evaluate the potential pharmacokinetic interaction between amitriptyline and sildenafil, brain and serum concentrations of amitriptyline were determined by HPLC. Sildenafil (1.25-20 mg/kg) as well as scopolamine (0.5 mg/kg) and its combination with sildenafil (1.25 mg/kg) did not affect the total immobility time duration. However, joint administration of scopolamine with sildenafil at doses of 2.5 and 5 mg/kg significantly reduced immobility time as compared to control group. Moreover, co-administration of scopolamine with sildenafil at the highest dose (5 mg/kg) significantly decreased immobility time as compared to scopolamine-treated group. Sildenafil (1.25, 2.5 and 5 mg/kg) significantly enhanced the antidepressant activity of amitriptyline (5 mg/kg). No changes in anti-immobility action of desipramine (20 mg/kg) in combination with sildenafil (5, 10 and 20 mg/kg) were observed. Sildenafil did not affect amitriptyline level in both brain and serum. In conclusion, the present study suggests that sildenafil may enhance the activity of antidepressant drugs which exhibit cholinolytic activity.

  11. Lowering barometric pressure aggravates depression-like behavior in rats.

    PubMed

    Mizoguchi, Hiroyuki; Fukaya, Kanoko; Mori, Rarami; Itoh, Mariko; Funakubo, Megumi; Sato, Jun

    2011-03-17

    Weather change has been known to influence the condition of patients with mood disorder. However, no animal studies have tested the influence of climatic factor on emotional impairment. In this study, we examined the effect of lowering barometric pressure (LP) in a climate-controlled room on immobility time in the forced swim test in rats, which is considered to be an index of behavioral despair (helplessness). When the rats were exposed to daily repeated forced swim, the immobility time gradually increased. This increment was inhibited by repeated administration of the antidepressant imipramine, suggesting that the immobility is an anxiety/depression-like behavior. LP exposure (20 hPa below the natural atmospheric pressure) further increased immobility time in rats submitted to repeated forced swim. In another series of experiments, we examined the effect of daily repeated LP exposure on the maintenance of immobility after withdrawal from 6-day repeated forced swim. When the rats were challenged with forced swim under natural atmospheric pressure on day 14 after the withdrawal, immobility time was significantly longer than in non-conditioned rats. These findings demonstrated that LP in the range of natural weather change augmented the depression-like behavior in rats.

  12. Endothermic force generation in skinned cardiac muscle from rat.

    PubMed

    Ranatunga, K W

    1999-08-01

    Isometric tension responses to rapid temperature jumps (T-jumps) of 2-6 degrees C were examined in skinned muscle fibre bundles isolated from papillary muscles of the rat heart. T-jumps were induced by an infra-red laser pulse (wave length 1.32 microm, pulse duration 0.2 ms) obtained from a Nd-YAG laser, which heated the fibres and bathing buffer solution in a 50 microl trough; the increased temperature by laser pulse was clamped at the high temperature by a Peltier system (see Ranatunga, 1996). In maximally Ca2+ -activated (pCa ca. 4.5) fibres, the relationship between tension and temperature was non-linear, the increase of active tension with temperature being more pronounced at lower temperatures (below ca. 20 degrees C). A T-jump at any temperature (range 3-35 degrees C) induced an initial step decrease of tension of variable amplitude (Phase 1), probably due to thermal expansion, and it was followed by a tension transient which resulted in a net rise of tension above the pre-T-jump level. The rate of net rise of tension (Phase 2b or endothermic force generation) was 7-10/s at ca. 12 degrees C and its Q10 was 6.3 (below 25 degrees C). In cases where the step decrease of tension in Phase 1 was prominent, an initial quick tension recovery phase (Phase 2a, 70-100/s at 12 degrees C) that did not contribute to a rise of tension above the pre-T-jump level, was also seen. This phase (Phase 2a) appeared to be similar to the quick tension recovery induced by a small length release and its rate increased with temperature with a Q10 of 1.8. In some cases where Phase 2a was present, a slower tension rise (Phase 3) was seen; its rate (ca. 5/s) was temperature-insensitive. The results show that the rate of endothermic force generation in cardiac fibres is clearly different from that of either fast-twitch or slow-twitch mammalian skeletal muscle fibres; implication of such fibre type-specific differences is discussed in relation to the difficulty in identifying the

  13. Effects of ketamine and N-methyl-D-aspartate on fluoxetine-induced antidepressant-related behavior using the forced swimming test.

    PubMed

    Owolabi, Rotimi Adegbenga; Akanmu, Moses Atanda; Adeyemi, Oluwole Isaac

    2014-04-30

    This study investigated the effects of ketamine on fluoxetine-induced antidepressant behavior using the forced swimming test (FST) in mice. In order to understand the possible role of N-methyl-d-aspartate (NMDA) neurotransmission in the antidepressant effect of fluoxetine, different groups of mice (n=10) were administered with acute ketamine (3mg/kg, i.p.), acute NMDA (75mg/kg and 150mg/kg, i.p.) and a 21-day chronic ketamine (15mg/kg, i.p./day) were administered prior to the administration of fluoxetine (20mg/kg, i.p.) in the mice. Antidepressant related behavior (immobility score) was measured using the forced swimming test. The results showed that the acute ketamine and fluoxetine alone treatments elicited a significant (p<0.05) reduction in immobility score compared with saline control. Furthermore, pre-treatment with acute ketamine significantly enhanced by the fluoxetine-induced decrease in immobility score. In contrast, pre-treatment with NMDA (150mg/kg) significantly (p<0.05) reversed fluoxetine-induced decrease in immobility score. On the other hand, chronic administration of ketamine significantly elicited an increase in immobility score as well as reversed the reduction induced by fluoxetine. Similarly, NMDA administration at both 75mg/kg and 150mg/kg increased immobility score in chronically administered ketamine groups. Furthermore, chronic administration of ketamine, followed by NMDA (75mg/kg) and fluoxetine significantly elevated the immobility score when compared with the group that received NMDA and fluoxetine but not chronically treated with ketamine. It can be suggested) that facilitation of NMDA transmission blocked fluoxetine-induced reduction in immobility score, while down-regulation of NMDA transmission is associated with increase in fluoxetine-induced antidepressant-related behavior in mice. Down-regulation of the NMDA transmission is proposed as an essential component of mechanism of suppression of depression related behaviors by

  14. Differential involvement of 5-HT(1A) and 5-HT(1B/1D) receptors in human interferon-alpha-induced immobility in the mouse forced swimming test.

    PubMed

    Zhang, Hongmei; Wang, Wei; Jiang, Zhenzhou; Shang, Jing; Zhang, Luyong

    2010-01-01

    Although Interferon-alpha (IFN-alpha, CAS 9008-11-1) is a powerful drug in treating several viral infections and certain tumors, a considerable amount of neuropsychiatric side-effects such as depression and anxiety are an unavoidable consequence. Combination with the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine (CAS 56296-78-7) significantly improved the situation. However, the potential 5-HT(1A) receptor- and 5-HT(1B) receptor-signals involved in the antidepressant effects are still unclear. The effects of 5-HT(1A) receptor- and 5-HT(1B) receptor signals were analyzed by using the mouse forced swimming test (FST), a predictive test of antidepressant-like action. The present results indicated that (1) fluoxetine (administrated intragastrically, 30 mg/kg; not subactive dose: 15 mg/kg) significantly reduced IFN-alpha-induced increase of the immobility time in the forced swimming test; (2) 5-HT(1A) receptor- and 5-HT(1B) receptor ligands alone or in combination had no effects on IFN-alpha-induced increase of the immobility time in the FST; (3) surprisingly, WAY 100635 (5-HT(1A) receptor antagonist, 634908-75-1) and 8-OH-DPAT(5-HT(1A) receptor agonist, CAS 78950-78-4) markedly enhanced the antidepressant effect of fluoxetine at the subactive dose (15 mg/kg, i. g.) on the IFN-alpha-treated mice in the FST. Further investigations showed that fluoxetine combined with WAY 100635 and 8-OH-DPAT failed to produce antidepressant effects in the FST. (4) Co-application of CGS 12066A (5-HT(1B) receptor agonist, CAS 109028-09-3) or GR 127935 (5-HT(1B/1D) receptor antagonist, CAS 148642-42-6) with fluoxetine had no synergistic effects on the IFN-alpha-induced increase of immobility time in FST. (5) Interestingly, co-administration of GR 127935, WAY 100635 and fluoxetine significantly reduced the IFN-alpha-induced increase in immobility time of FST, being more effective than co-administration of WAY 100635 and fluoxetine. All results suggest that (1) compared to

  15. Effect of High Intensity Interval and Continuous Swimming Training on Body Mass Adiposity Level and Serum Parameters in High-Fat Diet Fed Rats.

    PubMed

    da Rocha, Guilherme L; Crisp, Alex H; de Oliveira, Maria R M; da Silva, Carlos A; Silva, Jadson O; Duarte, Ana C G O; Sene-Fiorese, Marcela; Verlengia, Rozangela

    2016-01-01

    This study aimed to investigate the effects of interval and continuous training on the body mass gain and adiposity levels of rats fed a high-fat diet. Forty-eight male Sprague-Dawley rats were randomly divided into two groups, standard diet and high-fat diet, and received their respective diets for a period of four weeks without exercise stimuli. After this period, the animals were randomly divided into six groups (n = 8): control standard diet (CS), control high-fat diet (CH), continuous training standard diet (CTS), continuous training high-fat diet (CTH), interval training standard diet (ITS), and interval training high-fat diet (ITH). The interval and continuous training consisted of a swimming exercise performed over eight weeks. CH rats had greater body mass gain, sum of adipose tissues mass, and lower serum high density lipoprotein values than CS. The trained groups showed lower values of feed intake, caloric intake, body mass gain, and adiposity levels compared with the CH group. No significant differences were observed between the trained groups (CTS versus ITS and CTH versus ITH) on body mass gains and adiposity levels. In conclusion, both training methodologies were shown to be effective in controlling body mass gain and adiposity levels in high-fat diet fed rats. PMID:26904718

  16. Effect of High Intensity Interval and Continuous Swimming Training on Body Mass Adiposity Level and Serum Parameters in High-Fat Diet Fed Rats

    PubMed Central

    da Rocha, Guilherme L.; Crisp, Alex H.; de Oliveira, Maria R. M.; da Silva, Carlos A.; Silva, Jadson O.; Duarte, Ana C. G. O.; Sene-Fiorese, Marcela; Verlengia, Rozangela

    2016-01-01

    This study aimed to investigate the effects of interval and continuous training on the body mass gain and adiposity levels of rats fed a high-fat diet. Forty-eight male Sprague-Dawley rats were randomly divided into two groups, standard diet and high-fat diet, and received their respective diets for a period of four weeks without exercise stimuli. After this period, the animals were randomly divided into six groups (n = 8): control standard diet (CS), control high-fat diet (CH), continuous training standard diet (CTS), continuous training high-fat diet (CTH), interval training standard diet (ITS), and interval training high-fat diet (ITH). The interval and continuous training consisted of a swimming exercise performed over eight weeks. CH rats had greater body mass gain, sum of adipose tissues mass, and lower serum high density lipoprotein values than CS. The trained groups showed lower values of feed intake, caloric intake, body mass gain, and adiposity levels compared with the CH group. No significant differences were observed between the trained groups (CTS versus ITS and CTH versus ITH) on body mass gains and adiposity levels. In conclusion, both training methodologies were shown to be effective in controlling body mass gain and adiposity levels in high-fat diet fed rats. PMID:26904718

  17. Swimming training attenuates the morphological reorganization of the myocardium and local inflammation in the left ventricle of growing rats with untreated experimental diabetes.

    PubMed

    da Silva, Edson; Natali, Antônio José; da Silva, Márcia Ferreira; Gomes, Gilton de Jesus; da Cunha, Daise Nunes Queiroz; Toledo, Marileila Marques; Drummond, Filipe Rios; Ramos, Regiane Maria Soares; Dos Santos, Eliziária Cardoso; Novaes, Rômulo Dias; de Oliveira, Leandro Licursi; Maldonado, Izabel Regina dos Santos Costa

    2016-04-01

    Diabetic cardiomyopathy is associated with cardiac remodeling, myocardial dysfunction, low-grade inflammation, and reduced cardiac adiponectin in patients with type 1 diabetes mellitus (T1DM). Alternatively, physical exercise is an important strategy for the management of diabetes. This study aimed to investigate the influence of low-intensity swimming training in cardiac cytokines, structural remodeling, and cardiomyocyte contractile dysfunction in growing rats with untreated experimental DM. Thirty-day-old male Wistar rats were divided into four groups (n=14, per group): sedentary control (SC), exercised control (EC), sedentary diabetic (SD), and exercised diabetic (ED). Diabetes was induced by streptozotocin (60 mg kg(-1), i.p.). Animals from exercised groups swam (5 days/week, 90 min/day, loading up to 5% body weight around the animal's chest) for 8 weeks. The left ventricle (LV) was removed for molecular, morphological, and cardiomyocyte mechanical analysis. Diabetic animals presented cardiac remodeling with myocardial histoarchitectural disorganization, fibrosis, and necrosis. The capillary density was lower in diabetic animals. LV cardiomyocytes from diabetic animals exhibited more prolonged time to the peak of contraction and time to half relaxation than those from control animals. The cardiac levels of interleukin 10, nitric oxide, and total and high molecular weight (HMW) adiponectin were significantly decreased in diabetic animals. Exercise training reduced the level of TNF-α, increased capillary density, and attenuated the histopathological parameters assessed in diabetic rats. In conclusion, the cardiac structural remodeling coexists with reduced levels of total and HMW adiponectin, inflammation, and cardiomyocyte contractility dysfunction in experimental DM. More important, low-intensity swimming training attenuates part of these pathological changes, indicating the beneficial role for exercise in untreated T1DM. PMID:26896925

  18. The effect of low-level laser therapy on oxidative stress and functional fitness in aged rats subjected to swimming: an aerobic exercise.

    PubMed

    Guaraldo, Simone A; Serra, Andrey Jorge; Amadio, Eliane Martins; Antônio, Ednei Luis; Silva, Flávio; Portes, Leslie Andrews; Tucci, Paulo José Ferreira; Leal-Junior, Ernesto Cesar Pinto; de Carvalho, Paulo de Tarso Camillo

    2016-07-01

    The aim of the present study was to determine whether low-level laser therapy (LLLT) in conjunction with aerobic training interferes with oxidative stress, thereby influencing the performance of old rats participating in swimming. Thirty Wistar rats (Norvegicus albinus) (24 aged and six young) were tested. The older animals were randomly divided into aged-control, aged-exercise, aged-LLLT, aged-LLLT/exercise, and young-control. Aerobic capacity (VO2max(0.75)) was analyzed before and after the training period. The exercise groups were trained for 6 weeks, and the LLLT was applied at 808 nm and 4 J energy. The rats were euthanized, and muscle tissue was collected to analyze the index of lipid peroxidation thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. VO2 (0.75)max values in the aged-LLLT/exercise group were significantly higher from those in the baseline older group (p <0.01) and the LLLT and exercise group (p <0.05). The results indicate that the activities of CAT, SOD, and GPx were higher and statistically significant (p <0.05) in the LLLT/exercise group than those in the LLLT and exercise groups. Young animals presented lesser and statistically significant activities of antioxidant enzymes compared to the aged group. The LLLT/exercise group and the LLLT and exercise group could also mitigate the concentration of TBARS (p > 0.05). Laser therapy in conjunction with aerobic training may reduce oxidative stress, as well as increase VO2 (0.75)max, indicating that an aerobic exercise such as swimming increases speed and improves performance in aged animals treated with LLLT. PMID:26861983

  19. Swimming Droplets

    NASA Astrophysics Data System (ADS)

    Maass, Corinna C.; Krüger, Carsten; Herminghaus, Stephan; Bahr, Christian

    2016-03-01

    Swimming droplets are artificial microswimmers based on liquid droplets that show self-propelled motion when immersed in a second liquid. These systems are of tremendous interest as experimental models for the study of collective dynamics far from thermal equilibrium. For biological systems, such as bacterial colonies, plankton, or fish swarms, swimming droplets can provide a vital link between simulations and real life. We review the experimental systems and discuss the mechanisms of self-propulsion. Most systems are based on surfactant-stabilized droplets, the surfactant layer of which is modified in a way that leads to a steady Marangoni stress resulting in an autonomous motion of the droplet. The modification of the surfactant layer is caused either by the advection of a chemical reactant or by a solubilization process. Some types of swimming droplets possess a very simple design and long active periods, rendering them promising model systems for future studies of collective behavior.

  20. Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation of ERK.

    PubMed

    Wang, Zhen; Gu, Jianhua; Wang, Xueer; Xie, Kai; Luan, Qinsong; Wan, Nianqing; Zhang, Qun; Jiang, Hong; Liu, Dexiang

    2013-11-01

    Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities. There is only limited information about the antidepressant-like effect of resveratrol. The present study assessed whether resveratrol treatment (20, 40 and 80mg/kg, i.p., 21days) has an antidepressant-like effect on the forced swim test (FST) and tail suspension test (TST) in mice and examined what its molecular targets might be. The results showed that resveratrol administration produced antidepressant-like effects in mice, evidenced by the reduced immobility time in the FST and TST, while it had no effect on the locomotor activity in the open field test. Resveratrol treatment significantly reduced serum corticosterone levels, which had been elevated by the FST and TST. Moreover, resveratrol increased brain-derived neurotrophic factor (BDNF) protein and extracellular signal-regulated kinase (ERK) phosphorylation levels in the prefrontal cortex and hippocampus. All of these antidepressant-like effects of resveratrol were essentially similar to those observed with the clinical antidepressant, fluoxetine. These results suggest that the antidepressant-like effects of resveratrol in the FST and TST are mediated, at least in part, by modulating hypothalamic-pituitary-adrenal axis, BDNF and ERK phosphorylation expression in the brain region of mice. PMID:24125781

  1. Desipramine attenuates forced swim test-induced behavioral and neurochemical alterations in mice: an in vivo(1)H-MRS study at 9.4T.

    PubMed

    Kim, Sang-Young; Lee, Yun-Jung; Kim, Hyeonjin; Lee, Do-Wan; Woo, Dong-Cheol; Choi, Chi-Bong; Chae, Jeong-Ho; Choe, Bo-Young

    2010-08-12

    The forced swim test (FST) is a behavioral paradigm that is predicative of antidepressant activity in rodents. The objective of this study was to examine the effects of desipramine (DMI) pretreatment on behavioral and regional neurochemical responses in the left dorsolateral prefrontal cortex (DLPFC) and hippocampus of mice exposed to the FST using proton magnetic resonance spectroscopy ((1)H-MRS). An ultra short echo stimulated echo acquisition (STEAM) localization sequence (TR/TM/TE=5000/20/2.2ms) was used to measure in vivo proton spectra from the left DLPFC (voxel volume: 7microl) and hippocampus (6microl) of C57BL/6 mice at 9.4T and acquired proton spectra post-processed offline with LCModel. The FST induced significant increase of glutamate (Glu) and myo-inositol (mIns) concentrations in the left DLPFC and hippocampus, respectively. In addition, creatine+phosphocreatine (Cr+PCr) concentrations in the left DLPFC were significantly decreased as compared to control. The metabolic alterations induced by the FST were reverted to level similar to control by acute DMI administration. Our results suggest that glutamatergic activity and glial cell dysfunction may contribute to the pathophysiological mechanisms underlying depression and that modulation of synaptic neurotransmitter concentrations represents a potential target for antidepressant drug development. PMID:20542016

  2. NMDA and AMPA receptors are involved in the antidepressant-like activity of tianeptine in the forced swim test in mice.

    PubMed

    Wlaź, Piotr; Kasperek, Regina; Wlaź, Aleksandra; Szumiło, Michał; Wróbel, Andrzej; Nowak, Gabriel; Poleszak, Ewa

    2011-01-01

    It is known that tianeptine exhibits antidepressant-like activity. Its influence on the glutamatergic system is also known, but the mechanisms involved in this activity remain to be established. The aim of this study was to investigate the involvement of the glutamate pathway in the antidepressant-like action of tianeptine. We investigated the effects of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor ligands on tianeptine-induced activity in the forced swim test (FST) in mice. The antidepressant-like activity of tianeptine (30 m/kg, ip) was significantly antagonized by D-serine (100 nmol/mouse icv) and NBQX (10 mg/kg, ip). Moreover, low, ineffective doses of the glycine/NMDA site antagonist L-701,324 (1 mg/kg, ip) administered together with low, ineffective doses of tianeptine (20 mg/kg, ip) exhibited a significant reduction of immobility time in the FST. These doses of the examined agents, which did have an effect in the FST, did not alter locomotor activity. The present study indicates that the antidepressant-like activity of tianeptine in the FST involves both NMDA and AMPA receptors and suggests that the interaction between serotonergic and glutamatergic transmission may play an important role in the action of tianeptine.

  3. Synergistic antidepressant-like effect of the joint administration of caffeine and NMDA receptor ligands in the forced swim test in mice.

    PubMed

    Serefko, Anna; Szopa, Aleksandra; Wlaź, Aleksandra; Wośko, Sylwia; Wlaź, Piotr; Poleszak, Ewa

    2016-04-01

    The optimal treatment of depressed patients remains one of the most important challenges concerning depression. The identification of the best treatment strategies and development of new, safer, and more effective agents are crucial. The glutamatergic system seems to be a promising drug target, and consequently the use of the NMDA receptor ligands, particularly in co-administration with other substances exerting the antidepressant activity, has emerged among the new ideas. The objective of this study was to examine the effect of caffeine on the performance of mice treated with various NMDA modulators in the forced swim test. We demonstrated a significant interaction between caffeine (5 mg/kg) and the following NMDA receptor ligands: MK-801 (an antagonist binding in the ion channel, 0.05 mg/kg), CGP 37849 (an antagonist of the glutamate site, 0.312 mg/kg), L-701,324 (an antagonist of the glycine site, 1 mg/kg), and D-cycloserine (a high-efficacy partial agonist of the glycine site, 2.5 mg/kg), while the interaction between caffeine and the inorganic modulators, i.e., Zn(2+) (2.5 mg/kg) and Mg(2+) (10 mg/kg), was not considered as significant. Based on the obtained results, the simultaneous blockage of the adenosine and NMDA receptors may be a promising target in the development of new antidepressants.

  4. Differential effects of clonidine, lithium and quinine in the forced swimming test in mice for antidepressants: possible roles of serotoninergic systems.

    PubMed

    Bourin, M; Hascoet, M; Colombel, M C; Redrobe, J P; Baker, G B

    1996-08-01

    The forced swimming test (FST) is a behavioral test used to predict the efficacy of antidepressant (AD) treatments. In the present study, it was found that, when combined with clonidine, lithium or quinine, subactive doses of several types of ADs (tricyclics, 5-HT uptake inhibitors and atypical ADs) produced anti-immobility effects in mice. Clonidine (0.06 mg/kg) was found to potentiate the AD-like effects of all the drugs tested in the FST. More interesting is the additivity of gepirone with lithium (1 mEq/l), and ondansetron with quinine (0.5 mg/kg). The results of the present study are in favour of the potentiation of AD activity by clonidine via 5-HT2 receptors, lithium through 5-HT1A receptors, and quinine through 5-HT3 receptors. Further studies to examine in detail which of these three 5-HT receptors or their subtypes is the most important in the actions of individual ADs are warranted.

  5. NMDA and AMPA receptors are involved in the antidepressant-like activity of tianeptine in the forced swim test in mice.

    PubMed

    Wlaź, Piotr; Kasperek, Regina; Wlaź, Aleksandra; Szumiło, Michał; Wróbel, Andrzej; Nowak, Gabriel; Poleszak, Ewa

    2011-01-01

    It is known that tianeptine exhibits antidepressant-like activity. Its influence on the glutamatergic system is also known, but the mechanisms involved in this activity remain to be established. The aim of this study was to investigate the involvement of the glutamate pathway in the antidepressant-like action of tianeptine. We investigated the effects of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor ligands on tianeptine-induced activity in the forced swim test (FST) in mice. The antidepressant-like activity of tianeptine (30 m/kg, ip) was significantly antagonized by D-serine (100 nmol/mouse icv) and NBQX (10 mg/kg, ip). Moreover, low, ineffective doses of the glycine/NMDA site antagonist L-701,324 (1 mg/kg, ip) administered together with low, ineffective doses of tianeptine (20 mg/kg, ip) exhibited a significant reduction of immobility time in the FST. These doses of the examined agents, which did have an effect in the FST, did not alter locomotor activity. The present study indicates that the antidepressant-like activity of tianeptine in the FST involves both NMDA and AMPA receptors and suggests that the interaction between serotonergic and glutamatergic transmission may play an important role in the action of tianeptine. PMID:22358100

  6. Blockade of nociceptin/orphanin FQ-NOP receptor signalling produces antidepressant-like effects: pharmacological and genetic evidences from the mouse forced swimming test.

    PubMed

    Gavioli, E C; Marzola, G; Guerrini, R; Bertorelli, R; Zucchini, S; De Lima, T C M; Rae, G A; Salvadori, S; Regoli, D; Calo, G

    2003-05-01

    Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the NOP receptor, regulates several central functions such as pain transmission, learning and memory, fear and anxiety and feeding and locomotor activity. It has been recently reported that NOP receptor antagonists induce antidepressant-like effects in the mouse forced swimming test (FST), i.e. reduce immobility time. This assay was used in the present study for further investigating the involvement of the NOP receptor in depression states. In male Swiss mice, intracerebroventricular injection (i.c.v) of the novel NOP receptor antagonist, UFP-101 (1-10 nmol) dose-dependently reduced the immobility time (control 192 +/- 14 s, UFP-101 91 +/- 15 s). The effect of 3 or 10 nmol UFP-101 was fully or partially reversed, respectively, by the coadministration of 1 nmol N/OFQ, which was inactive per se. NOP receptor knockout mice showed a reduced immobility time compared with their wild-type littermates (wild-type 215 +/- 10 s, knockout 143 +/- 12 s). Moreover, i.c.v. injected UFP-101 (10 nmol) significantly reduced immobility time in wild-type mice but not in NOP receptor knockout animals. In conclusion, these results, obtained using a combined pharmacological and genetic approach, indicate that blockade of the N/OFQ-NOP receptor signalling in the brain produces antidepressant-like effects in the mouse FST. These findings support the NOP receptor as a candidate target for the development of innovative antidepressant drugs.

  7. Antidepressant-like effect of Hoodia gordonii in a forced swimming test in mice: evidence for involvement of the monoaminergic system

    PubMed Central

    Citó, M.C.O.; Silva, M.I.G.; Santos, L.K.X.; Fernandes, M.L.; Melo, F.H.C.; Aguiar, J.A.C.; Lopes, I.S.; Sousa, P.B.; Vasconcelos, S.M.M.; Macêdo, D.S.; Sousa, F.C.F.

    2014-01-01

    Hoodia gordonii is a plant species used traditionally in southern Africa to suppress appetite. Recently, it has been associated with a significant increase in blood pressure and pulse rate in women, suggesting sympathomimetic activity. The present study investigated the possible antidepressant-like effects of acute and repeated (15 days) administration of H. gordonii extract (25 and 50 mg/kg, po) to mice exposed to a forced swimming test (FST). Neurochemical analysis of brain monoamines was also carried out to determine the involvement of the monoaminergic system on these effects. Acute administration of H. gordonii decreased the immobility of mice in the FST without accompanying changes in general activity in the open-field test during acute treatment, suggesting an antidepressant-like effect. The anti-immobility effect of H. gordonii was prevented by pretreatment of mice with PCPA [an inhibitor of serotonin (5-HT) synthesis], NAN-190 (a 5-HT1A antagonist), ritanserin (a 5-HT2A/2C antagonist), ondansetron (a 5-HT3A antagonist), prazosin (an α1-adrenoceptor antagonist), SCH23390 (a D1 receptor antagonist), yohimbine (an α2-adrenoceptor antagonist), and sulpiride (a D2 receptor antagonist). A significant increase in 5-HT levels in the striatum was detected after acute administration, while 5-HT, norepinephrine and dopamine were significantly elevated after chronic treatment. Results indicated that H. gordonii possesses antidepressant-like activity in the FST by altering the dopaminergic, serotonergic, and noradrenergic systems. PMID:25493384

  8. Association between tryptophan hydroxylase-2 genotype and the antidepressant effect of citalopram and paroxetine on immobility time in the forced swim test in mice.

    PubMed

    Kulikov, Alexander V; Tikhonova, Maria A; Osipova, Daria V; Kulikov, Victor A; Popova, Nina K

    2011-10-01

    Tryptophan hydroxylase-2 (TPH2) is the rate limiting enzyme of serotonin synthesis in the brain. The 1473G allele of the C1473G polymorphism in mTPH2 gene is associated with reduced enzyme activity and serotonin synthesis rate in the mouse brain. Here, the influence of the 1473G allele on the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs), citalopram (2.5 or 5.0mg/kg) and paroxetine (5.0 or 10.0mg/kg), in the forced swim test was studied using B6-1473G and B6-1473C congenic mouse lines with the 1473G (decreased TPH2 activity) or 1473C (normal TPH2 activity) alleles, respectively, transferred to the genome of C57BL/6 mouse strain. Paroxetine (5.0 or 10.0mg/kg) and citalopram (2.5 or 5.0mg/kg) decreased immobility time in B6-1473C mice, while both doses of paroxetine and 2.5mg/kg of citaloprame did not alter immobility time in B6-1473G mice. However, 5.0mg/kg of citalopram reduced immobility in B6-1473G mice. The results provided genetic evidence of moderate association between 1473G allele and reduced sensitivity to SSRIs in mice.

  9. Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation of ERK.

    PubMed

    Wang, Zhen; Gu, Jianhua; Wang, Xueer; Xie, Kai; Luan, Qinsong; Wan, Nianqing; Zhang, Qun; Jiang, Hong; Liu, Dexiang

    2013-11-01

    Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities. There is only limited information about the antidepressant-like effect of resveratrol. The present study assessed whether resveratrol treatment (20, 40 and 80mg/kg, i.p., 21days) has an antidepressant-like effect on the forced swim test (FST) and tail suspension test (TST) in mice and examined what its molecular targets might be. The results showed that resveratrol administration produced antidepressant-like effects in mice, evidenced by the reduced immobility time in the FST and TST, while it had no effect on the locomotor activity in the open field test. Resveratrol treatment significantly reduced serum corticosterone levels, which had been elevated by the FST and TST. Moreover, resveratrol increased brain-derived neurotrophic factor (BDNF) protein and extracellular signal-regulated kinase (ERK) phosphorylation levels in the prefrontal cortex and hippocampus. All of these antidepressant-like effects of resveratrol were essentially similar to those observed with the clinical antidepressant, fluoxetine. These results suggest that the antidepressant-like effects of resveratrol in the FST and TST are mediated, at least in part, by modulating hypothalamic-pituitary-adrenal axis, BDNF and ERK phosphorylation expression in the brain region of mice.

  10. The effects of swimming exercise and supraphysiological doses of nandrolone decanoate on the testis in adult male rats: a transmission electron microscope study.

    PubMed

    Naraghi, M A; Abolhasani, F; Kashani, I; Anarkooli, I J; Hemadi, M; Azami, A; Barbarestani, M; Aitken, R J; Shokri, S

    2010-08-01

    Anabolic-androgenic steroids (AAS) are used in high doses by athletes to improve athletic ability, physical appearance, and muscle mass. Unfortunately, the abuse of these agents has significantly increased. It has been established that exercise and high doses of AAS may influence the hypothalamic-pituitary gonadal (H-P-G) axis, which can in turn affect the ultrastructure of the testes. However, the effect of the combination of exercise and high doses of AAS on the ultrastructure of the testes is not known. This study was undertaken in order to examine the combination effects of swimming exercise and supraphysiological doses of nandrolone decanoate on the ultrastructural changes in rat testes. Five groups of male Wistar strain albino rats were treated as follows for 8 weeks: solvent of nandrolone decanoate (peanut oil) as a vehicle (sham); nandrolone decanoate (ND) (10 mg/kg/week) - ND; exercise (1 h/day, 5 days a week) - exercise; ND (10 mg/kg/week) and exercise (1 h/day, 5 days a week) - ND-EX; and sedentary control without any injection or exercise - control. Ultrastructural changes in the rat testes were characterised by transmission electron microscopy. The number and size of Leydig cells were considerably decreased in the interstitial space in the experimental rats. The increased thickness and irregular wavy multilaminar appearance of basement membrane in the treated animals, especially in the ND-EX group, are associated with well developed myoid cells. Cytoplasm vacuolisation, vesicular-like crista of the mitochondria, numerous lipid droplets, and lysosome and phagolysosome in Sertoli cells were significantly observed in the experimental groups. Several apoptotic germ cells were considerably observed in the experimental rats (p ≤ 0.05). Exercise training seems to increase the extent of ultrastructural changes caused by supraphysiological doses of ND in rats, which in turn may affect fertility.

  11. The antidepressant-like effect of 7-fluoro-1,3-diphenylisoquinoline-1-amine in the mouse forced swimming test is mediated by serotonergic and dopaminergic systems.

    PubMed

    Pesarico, Ana Paula; Sampaio, Tuane Bazanella; Stangherlin, Eluza Curte; Mantovani, Anderson C; Zeni, Gilson; Nogueira, Cristina Wayne

    2014-10-01

    The aim of the present study was to investigate the role of monoaminergic system in the antidepressant-like action of 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI), a derivative of isoquinoline class, in Swiss mice. The antidepressant-like effect of FDPI was characterized in the modified forced swimming test (FST) and the possible mechanism of action was investigated by using serotonergic, dopaminergic and noradrenergic antagonists. Monoamine oxidase (MAO) activity and [(3)H]serotonin (5-HT) uptake were determined in prefrontal cortices of mice. The results showed that FDPI (1, 10 and 20mg/kg, i.g.) reduced the immobility time and increased the swimming time but did not alter climbing time in the modified FST. These effects were similar to those of paroxetine (8mg/kg, i.p.), a positive control. Pretreatments with p-chlorophenylalanine (100mg/kg, i.p., an inhibitor of 5-HT synthesis), WAY100635 (0.1mg/kg, s.c., 5-HT1A antagonist), ondansetron (1mg/kg, i.p., a 5-HT3 receptor antagonist), haloperidol (0.2mg/kg, i.p., a non-selective D2 receptor antagonist) and SCH23390 (0.05mg/kg, s.c., a D1 receptor antagonist) were effective to block the antidepressant-like effect of FDPI at a dose of 1mg/kg in the FST. Ritanserin (1mg/kg, i.p., a 5-HT2A/2C receptor antagonist), sulpiride (50mg/kg, i.p., a D2 and D3 receptor antagonist), prazosin (1mg/kg, i.p., an α1 receptor antagonist), yohimbine (1mg/kg, i.p., an α2 receptor antagonist) and propranolol (2mg/kg, i.p., a β receptor antagonist) did not modify the effect of FDPI in the FST. FDPI did not change synaptosomal [(3)H]5-HT uptake. At doses of 10 and 20mg/kg FDPI inhibited MAO-A and MAO-B activities. These results suggest that antidepressant-like effect of FDPI is mediated mostly by serotonergic and dopaminergic systems.

  12. C1473G polymorphism in mouse tph2 gene is linked to tryptophan hydroxylase-2 activity in the brain, intermale aggression, and depressive-like behavior in the forced swim test.

    PubMed

    Osipova, Daria V; Kulikov, Alexander V; Popova, Nina K

    2009-04-01

    Tryptophan hydroxylase-2 (TPH2) is the rate-limiting enzyme of brain serotonin synthesis. The C1473G polymorphism in the mouse tryptophan hydroxylase-2 gene affects the enzyme's activity. In the present study, we investigated the linkage between the C1473G polymorphism, enzyme activity in the brain, and behavior in the forced swim, intermale aggression, and open field tests using mice of the C57BL/6 (C/C) and CC57BR/Mv (G/G) strains and the B6-1473C (C/C) and B6-1473G (G/G) lines created by three successive backcrossings on C57BL/6. Mice of the CC57BR/Mv strain had decreased brain enzyme activity, aggression intensity, and immobility in the forced swim test, but increased locomotor activity and time spent in the central part of the open field arena compared with animals of the C57BL/6 strain. Mice of the B6-1473G line homozygous for the 1473G allele had lower TPH2 activity in the brain, aggression intensity, and immobility time in the forced swim test compared with animals of the B6-1473C line homozygous for the 1473C allele. No differences were found between the B6-1473G and B6-1473C mice in locomotor activity and time spent in the central part of the arena in the open field test. Thus, the C1473G polymorphism is involved in the determination of TPH2 activity and is linked to aggression intensity and forced-swim immobility in mice. At the same time, the polymorphism does not affect locomotion and anxiety-related behavior in the open field test. The B6-1473C and B6-1473G mice represent a valuable experimental model for investigating molecular mechanisms of serotonin-related behavior.

  13. Swimming Pools.

    ERIC Educational Resources Information Center

    Ministry of Housing and Local Government, London (England).

    Technical and engineering data are set forth on the design and construction of swimming pools. Consideration is given to site selection, pool construction, the comparative merits of combining open air and enclosed pools, and alternative uses of the pool. Guidelines are presented regarding--(1) pool size and use, (2) locker and changing rooms, (3)…

  14. Selective estrogen receptor-beta (SERM-beta) compounds modulate raphe nuclei tryptophan hydroxylase-1 (TPH-1) mRNA expression and cause antidepressant-like effects in the forced swim test.

    PubMed

    Clark, J A; Alves, S; Gundlah, C; Rocha, B; Birzin, E T; Cai, S-J; Flick, R; Hayes, E; Ho, K; Warrier, S; Pai, L; Yudkovitz, J; Fleischer, R; Colwell, L; Li, S; Wilkinson, H; Schaeffer, J; Wilkening, R; Mattingly, E; Hammond, M; Rohrer, S P

    2012-11-01

    Estrogen acts through two molecularly distinct receptors termed estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) which bind estradiol with similar affinities and mediate the effects of estrogen throughout the body. ERα plays a major role in reproductive physiology and behavior, and mediates classic estrogen signaling in such tissues as the uterus, mammary gland, and skeleton. ERβ, however, modulates estrogen signaling in the ovary, the immune system, prostate, gastrointestinal tract, and hypothalamus, and there is some evidence that ERβ can regulate ERα activity. Moreover, ERβ knockout studies and receptor distribution analyses in the CNS suggest that this receptor may play a role in the modulation of mood and cognition. In recent years several ERβ-specific compounds (selective estrogen receptor beta modulators; SERM-beta) have become available, and research suggests potential utility of these compounds in menopausal symptom relief, breast cancer prevention, diseases that have an inflammatory component, osteoporosis, cardiovascular disease, and inflammatory bowel disease, as well as modulation of mood, and anxiety. Here we demonstrate an antidepressant-like effect obtained using two SERM-beta compounds, SERM-beta1 and SERM-beta2. These compounds exhibit full agonist activity at ERβ in a cell based estrogen response element (ERE) transactivation assay. SERM-beta1 and 2 are non-proliferative with respect to breast as determined using the MCF-7 breast cancer cell-based assay and non-proliferative in the uterus as determined by assessing the effects of SERM-beta compounds on immature rat uterine weight and murine uterine weight. In vivo SERM-beta1 and 2 are brain penetrant and display dose dependent efficacy in the murine dorsal raphe assays for induction of tryptophan hydroxylase mRNA and progesterone receptor protein. These compounds show activity in the murine forced swim test and promote hippocampal neurogenesis acutely in rats. Taken

  15. The development of swimming power

    PubMed Central

    Gatta, Giorgio; Leban, Bruno; Paderi, Maurizio; Padulo, Johnny; Migliaccio, Gian Mario; Pau, Massimiliano

    2014-01-01

    Summary Purpose: the aim of this study was to investigate the effects of the transfer strength training method on swimming power. Methods: twenty male swimmers “master“ were randomly allocated to strength (n= 10, ST) and swimming training (n=10, SW) groups. Both groups performed six-weeks training based on swimming training for SW and strength training which consisted in a weight training session immediately followed by the maximum swimming velocity. The performance in both groups was assessed by Maximal-Mechanical-External-Power (MMEP) before and after the six-weeks period, using a custom ergometer that provided force, velocity, and power measurement in water. Results: a significant increased MMEP in ST group (5.73% with p< 0.05) was obtained by an increased strength (11.70% with p< 0.05) and a decreased velocity (4.99% with p> 0.05). Conversely, in the SW group there was a decreased in MMEP (7.31%; p< 0.05), force and velocity (4.16%, and 3.45; respectively p> 0.05). Conclusion: this study showed that the transfer training method, based on combination of weight training (in dry condition) immediately followed by fast swim (in water) significantly improves swimming-power in master. PMID:25767781

  16. Unsteady swimming of small organisms

    NASA Astrophysics Data System (ADS)

    Wang, Shiyan; Ardekani, Arezoo

    2012-11-01

    Small planktonic organisms ubiquitously display unsteady or impulsive motion to attack a prey or escape a predator in natural environments. Despite this, the role of unsteady hydrodynamic forces such as history and added mass forces on the low Reynolds number propulsion of small organisms is poorly understood. In this paper, we derive the fundamental equation of motion for an organism swimming by the means of surface distortion in a nonuniform flow at a low Reynolds number regime. We show that the history and added mass forces, that where traditionally neglected in the literature for small swimming organisms, cannot be neglected as the Stokes number increases above unity. For example, these unsteady inertial forces are of the same order as quasi-steady Stokes forces for Paramecium. Finally, we quantify the effects of convective inertial forces in the limit of small, but nonzero, Reynolds number regime. This work is supported by NSF grant CBET-1066545.

  17. Forced limb-use enhanced neurogenesis and behavioral recovery after stroke in the aged rats.

    PubMed

    Qu, H L; Zhao, M; Zhao, S S; Xiao, T; Song, C G; Cao, Y P; Jolkkonen, J; Zhao, C S

    2015-02-12

    Constraint-induced movement therapy (CIMT) after stroke enhances not only functional reorganization but also structural plasticity of the brain in the adult rats. We examined whether forced limb-use which mimicked CIMT could influence ischemia-induced neurogenesis, apoptosis and behavioral recovery in the aged rats. Aged rats were divided into a sham group, an ischemia group, and an ischemia group with forced limb-use. Focal cerebral ischemia was induced by injection of endothelin-1. Forced limb-use began on post-stroke day 7 by fitting a plaster cast around the unimpaired upper limbs of rats for 3 weeks. Behavioral recovery was evaluated by tapered/ledged beam-walking test on postoperative day 32. The expression of doublecortin, neuronal nuclei, glial fibrillary acidic protein and Iba-1 were measured by single or double immunohistochemistry, and apoptosis was measured by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay. The production of neuroblasts in the subventricular zone (SVZ) was significantly increased after stroke. Forced limb-use enhanced the proliferation of newborn neurons in the SVZ, as well as increased the long-term survival of newborn neurons. Furthermore, forced limb-use suppressed apoptosis and improved the motor functions after stroke in the aged rats. Forced limb-use exerted few effects on inflammation. Neither the number nor dendritic complexity of newborn granule cells in the hippocampus was affected by forced limb-use. Forced limb-use is effective in enhancing neurogenesis and behavioral recovery after stroke even in the aged rats. PMID:25463522

  18. NMDA-NO signaling in the dorsal and ventral hippocampus time-dependently modulates the behavioral responses to forced swimming stress.

    PubMed

    Diniz, Cassiano R A F; Casarotto, Plínio C; Joca, Sâmia R L

    2016-07-01

    Hodological and genetic differences between dorsal (DH) and ventral (VH) hippocampus may convey distinct behavioral roles. DH is responsible for mediating cognitive process, such as learning and memory, while VH modulates neuroendocrine and emotional-motivational responses to stress. Manipulating glutamatergic NMDA receptors and nitric oxide (NO) systems of the hippocampus induces important changes in behavioral responses to stress. Nevertheless, there is no study concerning functional differences between DH and VH in the modulation of behavioral responses induced by stress models predictive of antidepressant effects. Thus, this study showed that reversible blockade of the DH or VH of animals submitted to the forced swimming test (FST), by using cobalt chloride (calcium-dependent synaptic neurotransmission blocker), was not able to change immobility time. Afterwards, the NMDA-NO system was evaluated in the FST by means of intra-DH or intra-VH administration of NMDA receptor antagonist (AP7), NOS1 and sGC inhibitors (N-PLA and ODQ, respectively). Bilateral intra-DH injections after pretest or before test were able to induce antidepressant-like effects in the FST. On the other hand, bilateral VH administration of AP-7, N-PLA and ODQ induced antidepressant-like effects only when injected before the test. Administration of NO scavenger (C-PTIO) intra-DH, after pretest and before test, or intra-VH before test induced similar results. Increased NOS1 levels was associated to stress exposure in the DH. These results suggest that the glutamatergic-NO system of the DH and VH are both able to modulate behavioral responses in the FST, albeit with differential participation along time after stress exposure.

  19. Antidepressant-like effect of bis-eugenol in the mice forced swimming test: evidence for the involvement of the monoaminergic system.

    PubMed

    do Amaral, Jeferson Falcão; Silva, Maria Izabel Gomes; de Aquino Neto, Manuel Rufino; Moura, Brinell Arcanjo; de Carvalho, Alyne Mara Rodrigues; Vasconcelos, Patrícia Freire; Barbosa Filho, José Maria; Gutierrez, Stanley Juan Chavez; Vasconcelos, Silvânia Maria Mendes; Macêdo, Danielle Silveira; de Sousa, Francisca Cléa Florenço

    2013-10-01

    Dehydrodieugenol, known as bis-eugenol, is a eugenol ortho dimer, and both compounds were able to exhibit anti-inflammatory and antioxidant activities in previous studies. Furthermore, eugenol showed antidepressant-like effect; however, the biological actions of bis-eugenol on experimental models for screening antidepressant activity are still unknown. The present study investigated a possible antidepressant-like activity of bis-eugenol in the forced swimming test (FST) and tail suspension test (TST) in mice and the involvement in the monoaminergic system in this effect. In addition, a neurochemical analysis on brain monoamines of mice acutely treated with bis-eugenol was also conducted. Bis-eugenol decreased the immobility time in the FST and TST without accompanying changes in ambulation in the open field test at 10 mg/kg, i.p.. Nevertheless, it induced ambulation at 25 and 50 mg/kg doses. The anti-immobility effect of bis-eugenol (10 and 50 mg/kg, i.p.) was prevented by pretreatment of mice with p-chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist), SCH23390 (15 μg/kg, s.c., a dopamine D1 receptor antagonist) and sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist). Monoamines analysis using high-performance liquid chromatograph revealed significant increase in the 5-HT, NE and DA levels in brain striatum. The present study indicates that bis-eugenol possesses antidepressant-like activity in FST and TST by altering dopaminergic, serotonergic and noradrenergic systems function.

  20. Involvement of NMDA receptors and L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effects of topiramate in mice forced swimming test.

    PubMed

    Ostadhadi, Sattar; Khan, Muhammad Imran; Norouzi-Javidan, Abbas; Chamanara, Mohsen; Jazaeri, Farahnaz; Zolfaghari, Samira; Dehpour, Ahmad-Reza

    2016-04-01

    Topiramate (TPM) is an agent primarily used in the treatment of epilepsy. Using mice model of forced swimming test (FST) the current study was basically aimed to investigate the influence of TPM on depression by inhibiting NMDA receptor and nitric oxide-cGMP production. When TPM was administered in a dose of 20 and 30 mg/kg by i.p. route it reduced the immobility time during FST. However this effect of TPM (30 mg/kg, i.p.) in the FST was abolished when the mice were pretreated either with NMDA (75 mg/kg, i.p.), or l-arginine (750 mg/kg, i.p. NO precursor), or sildenafil (5mg/kg, i.p. Phosphodiesterase 5 inhibitor). The immobility time in the FST was reduced after administration of L-NAME (10mg/kg, i.p, a non-specific NOS inhibitor), 7-nitoinidazol (30 mg/kg, i.p. a nNOS inhibitor) or MK-801 (0.05 mg/kg, i.p, a NMDA receptor antagonist) in combination with a subeffective dose of TPM (10mg/kg, i.p.) as compared with single use of either drug. Co-administrated of lower doses of MK-801 (0.01 mg/kg) or L-NAME (1mg/kg) failed to effect immobility time. However, simultaneous administration of these two agents in the same doses with subeffective dose of TPM (10mg/kg, i.p.), reduced the immobility time during FST. None of these drugs were found to have a profound effect on the locomotor activity per se during the open field test. Taken together, our data demonstrates that TPM exhibit antidepressant-like effect which is accomplished either due to inhibition of NMDA receptors or NO-cGMP production.

  1. Antidepressant-like activity of selective serotonin reuptake inhibitors combined with a NK1 receptor antagonist in the mouse forced swimming test.

    PubMed

    Chenu, F; Guiard, B P; Bourin, M; Gardier, A M

    2006-09-25

    Substance P antagonists of the neurokinin-1 receptor type (NK1) have growing interest as new antidepressant therapies. It has been postulated that these drugs exert this putative therapeutic effect without direct interactions with serotonin (5-HT) neurons. In line with this assumption, previous intracerebral in vivo microdialysis experiments provided evidence that the NK1 receptor antagonists did not change basal cortical 5-HT levels. However, we found that increases in cortical 5-HT overflow caused by systemic injection of the selective serotonin reuptake inhibitor (SSRI), paroxetine was higher in freely moving (C57BL/6x129sv) NK1-/- mutants than in wild-type NK1+/+ mice. More recently, a pharmacological study has led to a similar conclusion since GR205171, a NK1 receptor antagonist, potentiated paroxetine-induced increases in cortical 5-HT dialysate following its acute systemic or intra-raphe administration to wild-type mice . In the present study, we tested whether an acute combination of SSRI and NK1 receptor antagonist could display antidepressant-like activity using the forced swimming test in Swiss mice. We found that a single systemic dose of GR205171 (10 and 30 mg/kg, i.p.) had no effect by itself. However, it selectively potentiated the antidepressant-like activity of subactive doses of two serotonergic antidepressant drugs, citalopram and paroxetine (without psychomotor stimulant activity), but not that of noradrenaline reuptake inhibitor, desipramine. In agreement with neurochemical data, the present study confirms that co-administration of a NK1 receptor antagonist with an antidepressant drug such as a SSRI may have a therapeutic potential to improve the treatment of major depressive episodes in human compared to SSRI alone.

  2. Involvement of NMDA receptors and L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effects of topiramate in mice forced swimming test.

    PubMed

    Ostadhadi, Sattar; Khan, Muhammad Imran; Norouzi-Javidan, Abbas; Chamanara, Mohsen; Jazaeri, Farahnaz; Zolfaghari, Samira; Dehpour, Ahmad-Reza

    2016-04-01

    Topiramate (TPM) is an agent primarily used in the treatment of epilepsy. Using mice model of forced swimming test (FST) the current study was basically aimed to investigate the influence of TPM on depression by inhibiting NMDA receptor and nitric oxide-cGMP production. When TPM was administered in a dose of 20 and 30 mg/kg by i.p. route it reduced the immobility time during FST. However this effect of TPM (30 mg/kg, i.p.) in the FST was abolished when the mice were pretreated either with NMDA (75 mg/kg, i.p.), or l-arginine (750 mg/kg, i.p. NO precursor), or sildenafil (5mg/kg, i.p. Phosphodiesterase 5 inhibitor). The immobility time in the FST was reduced after administration of L-NAME (10mg/kg, i.p, a non-specific NOS inhibitor), 7-nitoinidazol (30 mg/kg, i.p. a nNOS inhibitor) or MK-801 (0.05 mg/kg, i.p, a NMDA receptor antagonist) in combination with a subeffective dose of TPM (10mg/kg, i.p.) as compared with single use of either drug. Co-administrated of lower doses of MK-801 (0.01 mg/kg) or L-NAME (1mg/kg) failed to effect immobility time. However, simultaneous administration of these two agents in the same doses with subeffective dose of TPM (10mg/kg, i.p.), reduced the immobility time during FST. None of these drugs were found to have a profound effect on the locomotor activity per se during the open field test. Taken together, our data demonstrates that TPM exhibit antidepressant-like effect which is accomplished either due to inhibition of NMDA receptors or NO-cGMP production. PMID:26988103

  3. Involvement of nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tropisetron and ondansetron in mice forced swimming test and tail suspension test.

    PubMed

    Haj-Mirzaian, Arya; Kordjazy, Nastaran; Amiri, Shayan; Haj-Mirzaian, Arvin; Amini-Khoei, Hossien; Ostadhadi, Sattar; Dehpour, AhmadReza

    2016-06-01

    Antidepressant-like effects of 5-hydroxytryptamine subtype 3 (5-HT3) antagonists including tropisetron and ondansetron have been previously demonstrated in the literature. It was reported that stimulation of 5-HT3 receptors activate the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, which is involved in regulation of behavioral and emotional functions. In our study, treating animals with tropisetron (5, 10, and 30mg/kg) and ondansetron (0.01 and 0.1µg/kg) significantly decreased the immobility time in forced swimming test (FST) and tail-suspension test (TST). Co-administration of subeffective doses of tropisetron (1mg/kg) and ondansetron (0.001µg/kg) with subeffective dose of l-NAME (10mg/kg, nonselective NO synthase (NOS) inhibitor) and 7-nitroindazole (25mg/kg, neural NOS inhibitor) exerted antidepressant-like effect in FST and TST, while aminoguanidine (50mg/kg, inducible NOS inhibitor) did not enhance the antidepressant-like effect of 5-HT3 antagonists. Besides, l-arginine (750mg/kg, NO precursor) and sildenafil (5mg/kg, phosphodiesterase inhibitor) suppressed the anti-immobility effect of 5-HT3 antagonists. None of the treatments altered the locomotor behavior of mice in open-field test. Also, hippocampal (but not cortical) nitrite level was significantly lower in tropisetron and ondansetron-treated mice compared with saline-injected mice. Also, co-administration of 7-nitroindazole with tropisetron or ondansetron caused a significant decrease in hippocampal nitrite levels. In conclusion, we suggest that antidepressant-like effect of tropisetron and ondansetron are partially mediated by modulation of NO-cGMP pathway. PMID:27001377

  4. Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test.

    PubMed

    Ostadhadi, Sattar; Ahangari, Mohammad; Nikoui, Vahid; Norouzi-Javidan, Abbas; Zolfaghari, Samira; Jazaeri, Farahnaz; Chamanara, Mohsen; Akbarian, Reyhaneh; Dehpour, Ahmad-Reza

    2016-08-01

    Lamotrigine is an anticonvulsant agent that shows clinical antidepressant properties. The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) receptors and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) synthesis in possible antidepressant-like effect of lamotrigine in forced swimming test (FST) in mice. Intraperitoneal administration of lamotrigine (10mg/kg) decreased the immobility time in the FST (P<0.01) without any effect on locomotor activity in the open-field test (OFT), while higher dose of lamotrigine (30mg/kg) reduced the immobility time in the FST (P<0.001) as well as the number of crossings in the OFT. Pretreatment of animals with NMDA (75mg/kg), l-arginine (750mg/kg, a substrate for nitric oxide synthase [NOS]) or sildenafil (5mg/kg, a phosphodiesterase [PDE] 5 inhibitor) reversed the antidepressant-like effect of lamotrigine (10mg/kg) in the FST. Injection of l-nitroarginine methyl ester (l-NAME, 10mg/kg, a non-specific NOS inhibitor), 7-nitroindazole (30mg/kg, a neuronal NOS inhibitor), methylene blue (20mg/kg, an inhibitor of both NOS and soluble guanylate cyclase [sGC]), or MK-801 (0.05mg/kg), ketamine (1mg/kg), and magnesium sulfate (10mg/kg) as NMDA receptor antagonists in combination with a sub-effective dose of lamotrigine (5mg/kg) diminished the immobility time of animals in the FST compared with either drug alone. None of the drugs produced significant effects on the locomotor activity in the OFT. Based on our findings, it is suggested that the antidepressant-like effect of lamotrigine might mediated through inhibition of either NMDA receptors or NO-cGMP synthesis. PMID:27470415

  5. Either the dorsal hippocampus or the dorsolateral striatum is selectively involved in consolidation of forced swim-induced immobility depending on genetic background.

    PubMed

    Colelli, V; Campus, P; Conversi, D; Orsini, C; Cabib, S

    2014-05-01

    Healthy subjects differ in the memory system they engage to learn dual-solution tasks. Both genotype and stress experience could contribute to this phenotypic variability. The present experiments tested whether the hippocampus and the dorsal striatum, the core nodes of two different memory systems, are differently involved in 24 h retention of a stress-associated memory in two genetically unrelated inbred strains of mice. Mice from both the C57BL/6J and the DBA/2J inbred strains showed progressive increase of immobility during 10 min exposure to forced swim (FS) and retrieved the acquired levels of immobility when tested 24h later. The pattern of c-fos immunostaining promoted by FS revealed activation of a large number of brain areas in both strains, including CA1 and CA3 fields of the hippocampus. However, only DBA/2J mice showed activation of the dorsolateral striatum (DLS). In addition, FS induced a positive correlation between c-fos expression in the amygdala and CA1 and CA3 in C57BL/6J mice whereas it induced a positive correlation between c-fos expression in the amygdala and DLS in DBA/2J mice. Finally, temporary post-training inactivation of the dorsal hippocampus, by local infusion of lidocaine, prevented 24h retention of immobility in C57BL/6J mice only, whereas inactivation of the DLS prevented retention in DBA/2J mice only. These findings support the view that genetic factors can determine whether the dorsal hippocampus or the DLS are selectively engaged to consolidate stress-related memory.

  6. Delta(9)-tetrahydrocannabinol prolongs the immobility time in the mouse forced swim test: involvement of cannabinoid CB(1) receptor and serotonergic system.

    PubMed

    Egashira, Nobuaki; Matsuda, Tomomi; Koushi, Emi; Higashihara, Fuminori; Mishima, Kenichi; Chidori, Shozo; Hasebe, Nobuyoshi; Iwasaki, Katsunori; Nishimura, Ryoji; Oishi, Ryozo; Fujiwara, Michihiro

    2008-07-28

    In the present study, we investigated the effect of Delta(9)-tetrahydrocannabinol (THC), the principal psychoactive component of marijuana, on immobility time during the forced swim test. THC (2 and 6 mg/kg, i.p.) significantly prolonged the immobility time. In addition, THC at the same doses did not significantly affect locomotor activity in the open-field test. The selective cannabinoid CB(1) receptor antagonist rimonabant (3 mg/kg, i.p.) significantly reduced the enhancement of immobility by THC (6 mg/kg). Similarly, the selective serotonin (5-HT) reuptake inhibitor (SSRI) citalopram (10 mg/kg, i.p.) and 5-HT(1A/7) receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.3 mg/kg, i.p.) significantly reduced this THC-induced effect. Moreover, the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide dihydrochloride (WAY100635, 1 mg/kg, i.p.) and the postsynaptic 5-HT(1A) receptor antagonist MM-77 (0.1 mg/kg, i.p.) reversed this reduction effect of 8-OH-DPAT (0.3 mg/kg). In contrast, the selective 5-HT(7) receptor antagonist (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulfonyl]phenol hydrochloride (SB269970) had no effect on this reduction effect of 8-OH-DPAT. WAY100635 (1 mg/kg) also reversed the reduction effect of citalopram (10 mg/kg). These findings suggest that the 5-HT(1A) receptors are involved in THC-induced enhancement of immobility.

  7. The effect of Schisandra chinensis extracts on depression by noradrenergic, dopaminergic, GABAergic and glutamatergic systems in the forced swim test in mice.

    PubMed

    Yan, Tingxu; Xu, Mengjie; Wu, Bo; Liao, Zhengzheng; Liu, Zhi; Zhao, Xu; Bi, Kaishun; Jia, Ying

    2016-06-15

    Schisandra chinensis (Turcz.) Baill., as a Chinese functional food, has been widely used in neurological disorders including insomnia and Alzheimer's disease. The treatment of classical neuropsychiatric disorder depression is to be developed from Schisandra chinensis. The antidepressant-like effects of the Schisandra chinensis extracts (SCE), and their probable involvement in the serotonergic, noradrenergic, dopaminergic, GABAergic and glutamatergic systems were investigated by the forced swim test (FST). Acute administration of SCE (600 mg kg(-1), i.g.), a combination of SCE (300 mg kg(-1), i.g.) and reboxetine (a noradrenalin reuptake inhibitor, 2.5 mg kg(-1), i.p.) or imipramine (a TCA, 2 mg kg(-1), i.p.) reduced the immobility time in the FST. Pretreatment with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4, a selective noradrenergic neurotoxin, 50 mg kg(-1), i.p., 4 days), haloperidol (a non-selective D2 receptor antagonist, 0.2 mg kg(-1), i.p.), SCH 23390 (a selective D1 receptor antagonist, 0.03 mg kg(-1), i.p.), bicuculline (a competitive GABA antagonist, 4 mg kg(-1), i.p.) and N-methyl-d-aspartic acid (NMDA, an agonist at the glutamate site, 75 mg kg(-1), i.p.) effectively reversed the antidepressant-like effect of SCE (600 mg kg(-1), i.g.). However, p-chlorophenylalanine (pCPA, an inhibitor of 5-HT synthesis, 100 mg kg(-1), i.p., 4 days,) did not eliminate the reduced immobility time induced by SCE (600 mg kg(-1), i.g.). Moreover, the treatments did not change the locomotor activity. Altogether, these results indicated that SCE produced antidepressant-like activity, which might be mediated by the modification of noradrenergic, dopaminergic, GABAergic and glutamatergic systems.

  8. Swimming Lessons

    ERIC Educational Resources Information Center

    Goldman, Arthur

    2006-01-01

    In this article, the author talks about his experience as an 11-year-old swimmer and shares the lessons he learned as a member of the swim team. In his experience as one of the slowest team members, he discovered that slow and steady does not win the race, and when the focus is only on achievement, one loses the value of failure. As an adult, he…

  9. The effect of swimming exercise and powdered-Salicornia herbacea L. ingestion on glucose metabolism in STZ-induced diabetic rats

    PubMed Central

    Lee, Se Sil; Seo, Hyobin; Ryu, Sungpil; Kwon, Tae-Dong

    2015-01-01

    Purpose The purpose of this study is to observe the effects of Salicornia herbacea L. powder ingestion on carbohydrate metabolism in STZ-induced diabetic rats. Methods To achieve this objective, 35 Sprague-Dawley male rats were raised with feed mixed with Salicornia herbacia L. powder and given specific periods to swim for 5 weeks. There was no significant difference in the insulin increase rate while ingesting Salicornia herbacea L. powder and simultaneously exercising. Results Compared to the diabetes mellitus group, HOMA-IR was significantly decreased in the diabetes mellitus + exercise group, diabetes mellitus + Salicornia herbacea group, and the diabetes mellitus + Salicornia herbacea + exercise group. However, changes in blood glucose were significant in each group. Thus, for the result of GLUT-4 and GLUT-2, which are the glycose transporters of the liver and muscle, diabetes mellitus + exercise group, diabetes mellitus + Salicornia herbacea group, and diabetes mellitus + Salicornia herbacea + exercise group showed significantly higher expressions. The glycogen concentration of the liver and muscle was significantly increased in the diabetes mellitus + exercise group, diabetes mellitus + Salicornia herbacea group, and diabetes mellitus + Salicornia herbacea + exercise group. Conclusion With the results above, it seems that taking Salicornia herbacea L. powder and exercise will help prevent various diabetic complications. Therefore, the findings of this study could justify Salicornia herbacea L. powder with its basal data of physiological activities and pharmacological components as a type of health functional food. PMID:26525167

  10. Forced and voluntary exercise counteract insulin resistance in rats: the role of coping style.

    PubMed

    Boersma, Gretha J; Barf, R Paulien; Benthem, Lambertus; van Dijk, Gertjan; Scheurink, Anton J W

    2012-06-01

    There are large individual differences in the success rates of exercise intervention programs aimed at the prevention and treatment of obesity-related disorders. In the present study, we tested the hypothesis that differences in coping style may impact the success rates of these intervention programs. We tested insulin responses before and after voluntary wheel running in both passive (insulin resistant) Roman Low Avoidance (RLA) and proactive (insulin sensitive) Roman High Avoidance (RHA) rats using intravenous glucose tolerance tests (IVGTTs). To control for a potential difference between voluntary and forced exercise, we also included RLA and RHA rats that were subjected to forced running. We found the following: 1) when given the opportunity to run voluntarily in a running wheel, passive RLA rats run more than proactively than RHA rats; 2) voluntary exercise leads to a normalization of insulin responses during an IVGTTs in RLA rats; and 3) there were no behavioral and physiological differences in efficacy between voluntary and forced running. We conclude that exercise, both forced and voluntary, is a successful lifestyle intervention for the treatment of hyperinsulinemia, especially in individuals with a passive coping style. PMID:22609426

  11. Swimming ability in three Costa Rican dry forest rodents.

    PubMed

    Cook, W M; Timm, R M; Hyman, D E

    2001-01-01

    We investigated the swimming abilities of three Costa Rican dry forest rodents (Coues' rice rat. Oryzomys couesi, hispid cotton rat, Sigmodon hispidus, and spiny pocket mouse, Liomys salvini) associated with a large marsh, Laguna Palo Verde, using 90 s swim trials in a plastic container. Swimming ability was evaluated by observing the use of limbs and tail in the water, inclination to the surface, and diving and floating behavior. Rice rats could float, swim and dive, suggesting that they can exploit surface and underwater resources. Cotton rats swam at the water's surface, but were less skilled swimmers than rice rats. Spiny pocket mice tired quickly and had difficulty staying at the water's surface. Results suggest that differential swimming ability is related to the distribution of the three sympatric species within the marsh and adjacent forest habitats. PMID:12189799

  12. Hydrolyzed protein supplementation improves protein content and peroxidation of skeletal muscle by adjusting the plasma amino acid spectrums in rats after exhaustive swimming exercise: a pilot study

    PubMed Central

    2014-01-01

    Background This study was designed to evaluate the effects of hydrolyzed protein supplementation upon skeletal muscle total protein and peroxidation in rats following exhaustive swimming exercise. Methods Twenty-four rats were randomized to 4 experimental groups (n = 6 per group): control group fed standard diet without exercise (SD), exercise (EX), exercise plus standard diet for 72 hours (EX + SD), and exercise plus standard diet supplemented with hydrolyzed protein (2 g/kg/d) for 72 hours (EX + HP). Immediately following exercise, the EX group was euthanized for collecting plasma and skeletal muscle samples. The EX + SD and EX + HP groups were fed their respective diets for 72 hour still plasma and skeletal muscle collection. Skeletal muscle samples were used to measure levels of total protein (TP), malondialdehyde (MDA), and protein carbonyl (PC). Plasma samples were used to analyze the amino acids spectrum. Results Compared with the EX + SD, EX + HP presented the significantly increased TP (P = 0.02) and decreased MDA and PC levels (P = 0.035). MDA was negatively correlated with the methionine levels. Moreover, EX + HP maintained higher levels of plasmaleucine, isoleucine, and methionine than EX + SD, which may be associated with the increased skeletal muscle TP levels observed (P < 0.05). Conclusions These results collectively suggest that hydrolyzed protein supplementation can improve skeletal muscle TP and ameliorate peroxidation damage in rats subjected to exhaustive exercise stress, which may be, at least in part, related with the maintenance of plasma leucine, isoleucine, and methionine levels. PMID:24565110

  13. Behavioral action of ethanol in Porsolt's forced swim test: modulation by 3 alpha-hydroxy-5 alpha-pregnan-20-one.

    PubMed

    Hirani, K; Khisti, R T; Chopde, C T

    2002-12-01

    Ethanol is known to increase cortical and plasma content of GABAergic neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) which is responsible for some of its behavioral and electrophysiological effects. We have previously demonstrated the antidepressant like effect of 3alpha,5alpha-THP in mice. This study investigated the role of 3alpha,5alpha-THP in acute, chronic and withdrawal effects of ethanol using mouse forced swim test (FST) paradigm. While acute systemic ethanol (2 or 2.5 g/kg) administration exhibited an antidepressant like effect, its prolonged consumption produced tolerance to this effect and its withdrawal, on the other hand, elicited enhanced behavioral despair (depression). The antidepressant like effect of ethanol was potentiated by GABA(A) receptor agonist, muscimol (0.5 mg/kg, i.p.), 3alpha,5alpha-THP (0.5, 1 or 2 microg/mouse, i.c.v.) and by neurosteroidogenic drugs viz. selective serotonin reuptake inhibitor (SSRI), fluoxetine (5 or 20 mg/kg, i.p.), agonist at mitochondrial diazepam binding inhibitor receptor, FGIN 1-27 (0.5 or 1 microg/mouse, i.c.v.), or 11beta-hydroxylase inhibitor, metyrapone (0.5 or 1 microg/mouse, i.c.v.) which are known to increase endogenous 3alpha,5alpha-THP content. Furthermore, inhibition of the endogenous neurosteroid biosynthesis by drugs like 5alpha-reductase inhibitor, finasteride (50 mg/kg, s.c.), 3beta-hydroxysteroid dehydrogenase inhibitor, trilostane (30 mg/kg i.p.) or 3alpha-hydroxysteroid dehydrogenase inhibitor, indomethacin (5 mg/kg, i.p.) and GABA(A) receptor antagonist, bicuculline (1 mg/kg, i.p.) blocked the antidepressant like effect of ethanol. Withdrawal of ethanol from mice consuming it chronically displayed enhanced behavioral despair and elicited tolerance to antidepressant like action of acute ethanol (2.5, 3 or 3.5 g/kg). Moreover, sub-antidepressant doses (0.25 or 0.5 microg/mouse, i.c.v.) of 3alpha,5alpha-THP and fluoxetine (5 mg/kg, i.p.) but not imipramine (1 mg/kg, i

  14. Synergistic antidepressant-like effects between a kappa opioid antagonist (LY2444296) and a delta opioid agonist (ADL5859) in the mouse forced swim test.

    PubMed

    Huang, Peng; Tunis, Julia; Parry, Christopher; Tallarida, Ronald; Liu-Chen, Lee-Yuan

    2016-06-15

    Kappa opioid (KOP) receptor antagonists and delta opioid (DOP) receptor agonists have antidepressant-like effects in animal tests and may be useful for treatment-resistant depression in humans. In this study, we examined whether the combination of a KOP receptor antagonist and a DOP receptor agonist would produce a better than additive effect (i.e. synergy). LY2444296 is a short-acting selective nonpeptide KOP receptor antagonist. ADL5859 is a selective nonpeptide DOP receptor agonist which does not produce seizures and EEG disturbances. Each compound and combinations of the two were examined in the forced swim test (FST) one h post injection, a screening test for antidepressant-like effect, in male adult C57BL/6J mice (Jackson Lab). LY2444296 [subcutaneous (s.c.) injection] at 10 and 30mg/kg, but not 3mg/kg, significantly decreased immobility time in a dose-dependent manner. Intraperitoneal (i.p.) injections of ADL5859 also reduced immobility time dose-dependently at doses of 3 and 10mg/kg, but not at 1mg/kg. An analysis was conducted using the method of Tallarida and Raffa (2010), which employed dose equivalence. The relative potency of the drugs was determined to be LY2444296: ADL5859=1:0.28, which was the dose ratio for combination studies. Six combinations of the two compounds were tested in mice at a fixed dose ratio. We found that LY2444296 and ADL5859 yielded significant synergistic effects for the antidepressant-like effect at the combined dose ranging from 3.84mg/kg to 9.0mg/kg. ADL5859 (10mg/kg), LY2444296 (30mg/kg) and their combined dose (3.84mg/kg) had no effects on locomotor activities. Since the two drugs have distinct pharmacological profiles, such a synergism will allow use of lower doses of both drugs to achieve desired antidepressant effects with fewer side effects. PMID:27044434

  15. Antidepressant effect of pramipexole in mice forced swimming test: A cross talk between dopamine receptor and NMDA/nitric oxide/cGMP pathway.

    PubMed

    Ostadhadi, Sattar; Imran Khan, Muhammad; Norouzi-Javidan, Abbas; Dehpour, Ahmad-Reza

    2016-07-01

    Pramipexole is a dopamine D2 receptor agonist indicated for treating Parkinson disorder. This study was aimed to investigate the effect of pramipexole in forced swimming test (FST) in mice and the possible involvement of activation of D2 receptors and inhibition of N-methyl-d-aspartate (NMDA) receptors and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) on this effect. Intraperitoneal administration of pramipexole (1-3mg/kg) reduced the immobility time in the FST similar to fluoxetine (20mg/kg, i.p.). This effect of pramipexole (1mg/kg, i.p.) was ceased when mice were pretreated with haloperidol (0.15mg/kg, i.p,) and sulpiride (5mg/kg, i.p) as D2 receptor antagonists, NMDA (75mg/kg,i.p.), l-arginine (750mg/kg, i.p., a substrate for nitric oxide synthase) or sildenafil (5mg/kg, i.p., a phosphodiesterase 5 inhibitor). The administration of MK-801 (0.05mg/kg, i.p., a NMDA receptor antagonist) l-NG-Nitro arginine methyl ester (l-NAME, 10mg/kg, i.p., a non-specific nitric oxide synthase (NOS) inhibitor), 7-nitroindazole (30mg/kg, i.p., a neuronal NOS inhibitor) and methylene blue (10mg/kg, i.p.), an inhibitor of both NOS and soluble guanylyl cyclase (sGC) in combination with the sub-effective dose of pramipexole (0.3mg/kg, i.p.) reduced the immobility. Altogether, our data suggest that the antidepressant-like effect of pramipexole is dependent on the activation of D2 receptor and inhibition of either NMDA receptors and/or NO-cGMP synthesis. These results contribute to the understanding of the mechanisms underlying the antidepressant-like effect of pramipexole and reinforce the role of D2 receptors, NMDA receptors and l-arginine-NO-GMP pathway in the antidepressant mechanism of this agent. PMID:27261607

  16. 5-HT(1A)-receptor over-expressing mice: genotype and sex dependent responses to antidepressants in the forced swim-test.

    PubMed

    Günther, Lydia; Rothe, Julia; Rex, André; Voigt, Jörg-Peter; Millan, Mark J; Fink, Heidrun; Bert, Bettina

    2011-09-01

    Deficiencies in serotonergic neurotransmission are involved in the pathophysiology of depression. Due to its modulatory effect on serotonin (5-HT) release, the 5-HT(1A)-receptor is thought to play a decisive role in the therapy of this mood disorder. However, it is not fully understood how antidepressant effects are mediated by pre- and postsynaptic receptor sites. In this study we examined the impact of postsynaptic 5-HT(1A)-receptor over-expression in corticolimbic areas of male and female mice on the performance in the forced swim-test (FST). Furthermore, we investigated their response to the serotonin selective reuptake inhibitor (SSRI) citalopram in comparison to the selective noradrenaline reuptake inhibitor reboxetine, as well as the partial 5-HT(1A)-receptor agonists, buspirone and S 15535. Additionally, these drugs were evaluated in the open field-test in order to observe effects on motor activity. The density of 5-HT(1A)-receptors in discrete corticolimbic regions was determined in detail by quantitative autoradiography with [(3)H]8-OH-DPAT to investigate genotype as well as sex dependent differences in the expression pattern. [(3)H]8-OH-DPAT binding differed depending on sex with female mice of both genotypes displaying higher receptor binding in distinct brain areas. In the FST untreated male but not female over-expressing (OE) mice showed an antidepressant-like behaviour compared to wild-type (WT) mice. Citalopram yielded an antidepressant effect without influencing locomotor activity in OE mice but not in WT mice. Reboxetine had no antidepressant-like effect in OE mice, but sex-dependently in WT mice. The two partial agonists, buspirone and S 15535 produced no antidepressant-like activity in both genotypes and sexes, but aberrant motor effects. The antidepressant-like phenotype of male transgenic mice accounts for an involvement of postsynaptic 5-HT(1A)-receptors in the FST behaviour. In addition, the selective over-expression of postsynaptic 5-HT(1A

  17. Synergistic antidepressant-like effects between a kappa opioid antagonist (LY2444296) and a delta opioid agonist (ADL5859) in the mouse forced swim test.

    PubMed

    Huang, Peng; Tunis, Julia; Parry, Christopher; Tallarida, Ronald; Liu-Chen, Lee-Yuan

    2016-06-15

    Kappa opioid (KOP) receptor antagonists and delta opioid (DOP) receptor agonists have antidepressant-like effects in animal tests and may be useful for treatment-resistant depression in humans. In this study, we examined whether the combination of a KOP receptor antagonist and a DOP receptor agonist would produce a better than additive effect (i.e. synergy). LY2444296 is a short-acting selective nonpeptide KOP receptor antagonist. ADL5859 is a selective nonpeptide DOP receptor agonist which does not produce seizures and EEG disturbances. Each compound and combinations of the two were examined in the forced swim test (FST) one h post injection, a screening test for antidepressant-like effect, in male adult C57BL/6J mice (Jackson Lab). LY2444296 [subcutaneous (s.c.) injection] at 10 and 30mg/kg, but not 3mg/kg, significantly decreased immobility time in a dose-dependent manner. Intraperitoneal (i.p.) injections of ADL5859 also reduced immobility time dose-dependently at doses of 3 and 10mg/kg, but not at 1mg/kg. An analysis was conducted using the method of Tallarida and Raffa (2010), which employed dose equivalence. The relative potency of the drugs was determined to be LY2444296: ADL5859=1:0.28, which was the dose ratio for combination studies. Six combinations of the two compounds were tested in mice at a fixed dose ratio. We found that LY2444296 and ADL5859 yielded significant synergistic effects for the antidepressant-like effect at the combined dose ranging from 3.84mg/kg to 9.0mg/kg. ADL5859 (10mg/kg), LY2444296 (30mg/kg) and their combined dose (3.84mg/kg) had no effects on locomotor activities. Since the two drugs have distinct pharmacological profiles, such a synergism will allow use of lower doses of both drugs to achieve desired antidepressant effects with fewer side effects.

  18. Reduction of circulating and selective limbic brain levels of (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP) following forced swim stress in C57BL/6J mice

    PubMed Central

    Maldonado-Devincci, Antoniette M.; Beattie, Matthew C.; Morrow, Danielle H.; McKinley, Raechel E.; Cook, Jason B.; O’Buckley, Todd K.

    2014-01-01

    Rationale Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, and GABAergic neuroactive steroids contribute to homeostatic regulation of this circuitry. Acute forced swim stress (FSS) increases plasma, cortical, and hypothalamic (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP) levels in rats. However, there have not been systemic investigations of acute stress on changes in plasma and brain levels of 3α,5α-THP in mouse models. Objectives The present experiments aimed to assess circulating and local brain levels of 3α,5α-THP following acute FSS in C57BL/6J mice. Methods Mice were exposed to FSS (10 min), and 50 min later, blood and brains were collected. Circulating pregnenolone and 3α,5α-THP levels were assessed in serum. Free-floating brain sections (40 µm, four to five sections/region) were immunostained and analyzed in cortical and limbic brain structures. Results FSS decreased circulating 3α,5α-THP (−41.6± 10.4 %) and reduced 3α,5α-THP immunolabeling in the paraventricular nucleus of the hypothalamus (−15.2±5.7 %), lateral amygdala (LA, −31.1±13.4 %), and nucleus accumbens (NAcc) shell (−31.9±14.6). Within the LA, vesicular glutamate transporter 1 (VGLUT1) and vesicular GABA transporter were localized in 3α,5α-THP-positively stained cells, while in the NAcc shell, only VGLUT1 was localized in 3α,5α-THP-positively stained cells, suggesting that both glutamatergic and GABAergic cells within the LA are 3α,5α-THP-positive, while in the NAcc shell, 3α,5α-THP only localizes to glutamatergic cells. Conclusions The decrease in circulating and brain levels of 3α,5α-THP may be due to alterations in the biosynthesis/ metabolism or changes in the regulation of the HPA axis following FSS. Changes in GABAergic neuroactive steroids in response to stress likely mediate functional adaptations in neuronal activity. This may provide a potential targeted therapeutic avenue to address maladaptive stress responsivity. PMID:24744202