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Sample records for adult rats effects

  1. Behavioral effects of dehydroepiandrosterone in adult male rats.

    PubMed

    Fedotova, Julia; Sapronov, Nikolay

    2004-09-01

    It is well-documented that dehydroepiandrosterone (DHEA) exhibits various behavioral effects in rodents, at least one of which is modulation of learning/memory processes in several test paradigms. However, little is known about the influence of DHEA on cognitive performance in the adult rodents. This work was designed to determine whether chronic DHEA administration during 10 days in the high (0.7 mg/kg, s.c.) or low (0.1 mg/kg, s.c.) doses has any effect on learning/memory abilities and behavior in the adult male rats (5- to 6-month old). Effect of DHEA was estimated in active and passive avoidance tasks, behavior was registered in the elevated "plus" maze and the "open field" test. DHEA in the high dose significantly (p<0.05) increased time spent and the number of enterings in the "open" arms of the elevated "plus" maze in intact male rats as compared with the control rats. DHEA in the low dose significantly (p<0.05) decreased horizontal and vertical locomotor activity and grooming behavior, whereas DHEA in the high dose did not significantly modify behavior in intact rats as compared with control group. Results of the ANOVA on passive avoidance performance revealed no statistically significant differences among the groups receiving DHEA in the high or low doses as compared to the control. However, DHEA in the low dose significantly (p<0.05) reduced the number of correct avoidance responses in intact rats as compared to the control rats, while in rats treated with the high dose DHEA, the active avoidance performance did not differ significantly from the control. Thus, chronic DHEA administration has a modulatory action on the learning and behavior of the adult male rats.

  2. Effect of dehydroepiandrosterone on avoidance behavior of adult male rats.

    PubMed

    Fedotova, Yu O; Goncharov, N P; Sapronov, N S

    2004-07-01

    We studied the effect of repeated intraperitoneal treatment with dehydroepiandrosterone in doses of 0.1 and 0.7 mg/kg on conditioned-response activity and behavior of adult male rats. The effect of dehydroepiandrosterone on learning was estimated in conditioned active and passive avoidance response paradigms. Chronic administration of dehydroepiandrosterone in low and high doses had no effect on retention of conditioned passive avoidance response in adult male rats 24 h after learning. However, chronic administration of dehydroepiandrosterone in low dose impaired acquisition of the conditioned active avoidance response. It should be emphasized that chronic administration of dehydroepiandrosterone in high dose did not modulate acquisition and retention of this reaction.

  3. Effects of environmental tobacco smoke on adult rat brain biochemistry.

    PubMed

    Fuller, Brian F; Gold, Mark S; Wang, Kevin K W; Ottens, Andrew K

    2010-05-01

    Environmental tobacco smoke (ETS) has been linked to deleterious health effects, particularly pulmonary and cardiac disease; yet, the general public considers ETS benign to brain function in adults. In contrast, epidemiological data have suggested that ETS impacts the brain and potentially modulates neurodegenerative disease. The present study begins to examine yet unknown biochemical effects of ETS on the adult mammalian brain. In the developed animal model, adult male rats were exposed to ETS 3 h a day for 3 weeks. Biochemical data showed altered glial fibrillary acid protein levels as a main treatment effect of ETS, suggestive of reactive astrogliosis. Yet, markers of oxidative and cell stress were unaffected by ETS exposure in the brain regions examined. Increased proteolytic degradation of alphaII-spectrin by caspase-3 and the dephosphorylation of serine(116) on PEA-15 indicated greater apoptotic cell death modulated by the extrinsic pathway in the brains of ETS-exposed animals. Further, beta-synuclein was upregulated by ETS, a neuroprotective protein previously reported to exhibit anti-apoptotic and anti-fibrillogenic properties. These findings demonstrate that ETS exposure alters the neuroproteome of the adult rat brain, and suggest modulation of inflammatory and cell death processes.

  4. Perinatal effect of methamphetamine on nociception in adult Wistar rats.

    PubMed

    Yamamotová, A; Hrubá, L; Schutová, B; Rokyta, R; Šlamberová, R

    2011-02-01

    Methamphetamine is a psychostimulant drug which causes the release of monoamine neurotransmitters. Although drugs of abuse are known to have analgesic effects, there is a lack of evidence regarding the effect of prenatal exposure to methamphetamine on nociception in adulthood. Adult Wistar rats whose mothers had received daily exposure to methamphetamine (5 mg/kg; s.c.) or saline, during gestation or gestation and lactation periods, were examined for: (1) gender differences in nociception; (2) an association between nociception and gross-motor behavior in the plantar test; (3) effects of cross-fostering on nociception; and (4) analgesic effects of an acute injection of methamphetamine (1 mg/kg s.c.). Nociception was tested using the plantar test on postnatal days 85-90. Prenatal methamphetamine increased sensitivity to pain on forelimbs (p<0.0001) and hind limbs (p<0.05) in females only. Prenatal methamphetamine treated male rats fostered by adoptive injection stressed mothers had higher sensitivity to pain than prenatally injection stressed rats fostered by methamphetamine treated mothers (p<0.05). Acute methamphetamine induced analgesia faster in prenatally methamphetamine exposed rats than in controls. In all groups, analgesia increased in the cranio-caudal direction (p<0.0001). From our behavioral data it can be concluded that exposure to methamphetamine during the prenatal period completely dissociates the relationship between nociception and intensity of overall behavior observed in intact animals in adulthood. Thus, our results indicate that perinatal exposure to psychostimulants may have long-term impact on several functions related to dopaminergic system. Copyright © 2010 ISDN. Published by Elsevier Ltd. All rights reserved.

  5. Sidestream cigarette smoke exposure effects on baroreflex in adult rats.

    PubMed

    Valenti, Vitor E; Abreu, Luiz Carlos de; Ferreira, Celso

    2011-02-01

    It has been evidenced in the literature that exposure to cigarette smoke causes hypertension in rats; however, it has not been demonstrated if the baroreflex function is impaired before the animal becomes hypertensive. We evaluated short-term effects of sidestream cigarette smoke (SSCS) exposure on baroreflex function in Wistar normotensive rats. Rats were exposed to SSCS during three weeks, 180 minutes, five days per week, at a concentration of monoxide carbon between 100-300 ppm. Mean arterial pressure (MAP) and heart rate (HR) were evaluated through cannulation of the femoral vein and artery. There was no significant difference between control and SSCS groups regarding basal mean arterial pressure and heart rate, sympathetic and parasympathetic components of the baroreflex function. Our data suggest that three weeks of exposure to SSCS is not enough to significantly impair cardiovascular parameters and baroreflex sensitivity in normotensive Wistar rats.

  6. Differential effects of delta9-THC on learning in adolescent and adult rats.

    PubMed

    Cha, Young May; White, Aaron M; Kuhn, Cynthia M; Wilson, Wilkie A; Swartzwelder, H S

    2006-03-01

    Marijuana use remains strikingly high among young users in the U.S., and yet few studies have assessed the effects of delta9-tetrahydrocannabinol (THC) in adolescents compared to adults. This study measured the effects of THC on male adolescent and adult rats in the Morris water maze. In Experiment 1, adolescent (PD=30-32) and adult (PD=65-70) rats were treated acutely with 5.0 mg/kg THC or vehicle while trained on the spatial version of the water maze on five consecutive days. In Experiment 2, adolescent and adult rats were treated acutely with 2.5 or 10.0 mg/kg THC or vehicle while trained on either the spatial and non-spatial versions of the water maze. In Experiment 3, adolescent and adult rats were treated with 5.0 mg/kg THC or vehicle daily for 21 days, and were trained on the spatial and then the non-spatial versions of the water maze task four weeks later in the absence of THC. THC impaired both spatial and nonspatial learning more in adolescents than in adults at all doses tested. However, there were no long-lasting significant effects on either spatial or non-spatial learning in rats that had been previously exposed to THC for 21 days. This developmental sensitivity is analogous to the effects of ethanol, another commonly used recreational drug.

  7. Enduring and sex-specific effects of adolescent social isolation in rats on adult stress reactivity.

    PubMed

    Weintraub, Ari; Singaravelu, Janani; Bhatnagar, Seema

    2010-07-09

    In adolescence, gender differences in rates of affective disorders emerge. For both adolescent boys and girls, peer relationships are the primary source of life stressors though adolescent girls are more sensitive to such stressors. Social stressors are also powerful stressors for non-human social species like rodents. In a rat model, we examined how social isolation during adolescence impacts stress reactivity and specific neural substrates in adult male and female rats. Rats were isolated during adolescence by single housing from day 30 to 50 of age and control rats were group housed. On day 50, isolated rats and control rats were re-housed in same-treatment same-sex groups. Adult female rats isolated as adolescents exhibited increased adrenal responses to acute and to repeated stress and exhibited increased hypothalamic vasopressin mRNA and BDNF mRNA in the CA3 hippocampal subfield. In contrast, adult male rats isolated as adolescents exhibited a lower corticosterone response to acute stress, exhibited a reduced state of anxiety as assessed in the elevated plus maze and reduced Orexin mRNA compared to adult males group-housed as adolescents. These data point to a markedly different impact of isolation experienced in adolescence on endocrine and behavioral endpoints in males compared to females and identify specific neural substrates that may mediate the long-lasting effects of stress in adolescence.

  8. The effects of acute alcohol on motor impairments in adolescent, adult, and aged rats.

    PubMed

    Ornelas, Laura C; Novier, Adelle; Van Skike, Candice E; Diaz-Granados, Jaime L; Matthews, Douglas B

    2015-03-01

    Acute alcohol exposure has been shown to produce differential motor impairments between aged and adult rats and between adolescent and adult rats. However, the effects of acute alcohol exposure among adolescent, adult, and aged rats have yet to be systematically investigated within the same project using a dose-dependent analysis. We sought to determine the age- and dose-dependent effects of acute alcohol exposure on gross and coordinated motor performance across the rodent lifespan. Adolescent (PD 30), adult (PD 70), and aged (approximately 18 months) male Sprague-Dawley rats were tested on 3 separate motor tasks: aerial righting reflex (ARR), accelerating rotarod (RR), and loss of righting reflex (LORR). In a separate group of animals, blood ethanol concentrations (BEC) were determined at multiple time points following a 3.0 g/kg ethanol injection. Behavioral tests were conducted with a Latin square repeated-measures design in which all animals received the following doses: 1.0 g/kg or 2.0 g/kg alcohol or saline over 3 separate sessions via intraperitoneal (i.p.) injection. During testing, motor impairments were assessed on the RR 10 min post-injection and on ARR 20 min post-injection. Aged animals spent significantly less time on the RR when administered 1.0 g/kg alcohol compared to adult rats. In addition, motor performance impairments significantly increased with age after 2.0 g/kg alcohol administration. On the ARR test, aged rats were more sensitive to the effects of 1.0 g/kg and 2.0 g/kg alcohol compared to adolescents and adults. Seven days after the last testing session, animals were given 3.0 g/kg alcohol and LORR was examined. During LORR, aged animals slept longer compared to adult and adolescent rats. This effect cannot be explained solely by BEC levels in aged rats. The present study suggests that acute alcohol exposure produces greater motor impairments in older rats when compared to adolescent and adult rats and begins to establish a

  9. Effects of Neonatal Overfeeding on Juvenile and Adult Feeding and Energy Expenditure in the Rat

    PubMed Central

    Stefanidis, Aneta; Spencer, Sarah J.

    2012-01-01

    Overfeeding during perinatal life leads to an overweight phenotype that persists throughout the juvenile stage and into adulthood, however, the mechanim(s) underlying this effect are poorly understood. We hypothesized that obesity due to neonatal overfeeding is maintained by changes in energy expenditure and that these changes differ between males and females. We investigated feeding, physical activity, hormonal and metabolic alterations that occur in adult rats made obese by having been nursed in small litters (SL) compared with those from control litters (CL). There were no differences in absolute food intake between the groups, and juvenile and adult SL rats ate less chow per gram body weight than the CL did in the dark (active) phase. Juvenile, but not adult SL rats did have reduced whole body energy expenditure, but there were no differences between the groups by the time they reached adulthood. Adult SL females (but not males) had reduced brown adipose tissue (BAT) temperatures compared with CL in the first half of the dark phase. Our results indicate a persistent overweight phenotype in rats overfed as neonates is not associated with hyperphagia at any stage, but is reflected in reduced energy expenditure into the juvenile phase. The reduced dark phase BAT activity in adult SL females is not sufficient to reduce total energy expenditure at this stage of life and there is an apparently compensatory effect that prevents SL and CL from continuing to diverge in weight that appears between the juvenile and adult stages. PMID:23251693

  10. The Effects of Inflammatory Tooth Pain on Anxiety in Adult Male Rats

    PubMed Central

    Raoof, Maryam; Ebrahimnejad, Hamed; Abbasnejad, Mehdi; Amirkhosravi, Ladan; Raoof, Ramin; Esmaeili Mahani, Saeed; Ramazani, Mohsen; Shokouhinejad, Noushin; Khoshkhounejad, Mehrfam

    2016-01-01

    Introduction: This study aimed to examine the effects of induced inflammatory tooth pain on anxiety level in adult male rats. Methods: The mandibular incisors of 56 adult male rats were cut off and prefabricated crowns were fixed on the teeth. Formalin and capsaicin were injected intradentally to induce inflammatory tooth pain. Diazepam treated group received diazepam 30 minutes before intradental injection. The anxiety-related behavior was evaluated with elevated plus maze test. Results: Intradental application of chemical noxious stimuli, capsaicin and formalin, significantly affected nociceptive behaviors (P<0.001). Capsaicin (P<0.001) and formalin (P<0.01) significantly increased the anxiety levels in rats by decrease in the duration of time spent in open arm and increase in the duration of time spent in closed arm. Rats that received capsaicin made fewer open arm entries compared to the control animals (P<0.05). Capsaicin (P<0.001) and formalin (P<0.01) treated rats showed more stretch attend postures compared to the control and sham operated animals. In diazepampretreated rats, capsaicin induced algesic effect was prevented (P<0.001). Conclusion: Inflammatory pulpal pain has anxiogenic effect on rats, whereas diazepam premedication showed both anxiolytic and pain reducing effects. PMID:27563419

  11. The Effects of Inflammatory Tooth Pain on Anxiety in Adult Male Rats.

    PubMed

    Raoof, Maryam; Ebrahimnejad, Hamed; Abbasnejad, Mehdi; Amirkhosravi, Ladan; Raoof, Ramin; Esmaeili Mahani, Saeed; Ramazani, Mohsen; Shokouhinejad, Noushin; Khoshkhounejad, Mehrfam

    2016-07-01

    This study aimed to examine the effects of induced inflammatory tooth pain on anxiety level in adult male rats. The mandibular incisors of 56 adult male rats were cut off and prefabricated crowns were fixed on the teeth. Formalin and capsaicin were injected intradentally to induce inflammatory tooth pain. Diazepam treated group received diazepam 30 minutes before intradental injection. The anxiety-related behavior was evaluated with elevated plus maze test. Intradental application of chemical noxious stimuli, capsaicin and formalin, significantly affected nociceptive behaviors (P<0.001). Capsaicin (P<0.001) and formalin (P<0.01) significantly increased the anxiety levels in rats by decrease in the duration of time spent in open arm and increase in the duration of time spent in closed arm. Rats that received capsaicin made fewer open arm entries compared to the control animals (P<0.05). Capsaicin (P<0.001) and formalin (P<0.01) treated rats showed more stretch attend postures compared to the control and sham operated animals. In diazepampretreated rats, capsaicin induced algesic effect was prevented (P<0.001). Inflammatory pulpal pain has anxiogenic effect on rats, whereas diazepam premedication showed both anxiolytic and pain reducing effects.

  12. PREPUBERTAL EXPOSURES TO COMPOUNDS THAT INCREASE PROLACTIN SECRETION IN THE MALE RAT: EFFECTS ON ADULT PROSTATE

    EPA Science Inventory

    Prepubertal exposure to compounds that increase prolactin secretion in the male rat: effects on the adult prostate.

    Stoker TE, Robinette CL, Britt BH, Laws SC, Cooper RL.

    Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effec...

  13. EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON THYROID HORMONE STATUS IN ADULT AND NEONATAL RATS

    EPA Science Inventory

    EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON THYROID HORMONE STATUS IN ADULT AND NEONATAL RATS. M.N. Logan1, J.R. Thibodeaux2, R.G. Hanson2, C. Lau2. 1North Carolina Central University, Durham, NC, 2Reprod. Tox. Div. NHEERL, US EPA, Research Triangle Park, NC.

    Perfluor...

  14. PREPUBERTAL EXPOSURES TO COMPOUNDS THAT INCREASE PROLACTIN SECRETION IN THE MALE RAT: EFFECTS ON ADULT PROSTATE

    EPA Science Inventory

    Prepubertal exposure to compounds that increase prolactin secretion in the male rat: effects on the adult prostate.

    Stoker TE, Robinette CL, Britt BH, Laws SC, Cooper RL.

    Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effec...

  15. Effect of different doses of Malaysian honey on reproductive parameters in adult male rats.

    PubMed

    Mohamed, M; Sulaiman, S A; Jaafar, H; Sirajudeen, K N S

    2012-05-01

    The aim of this study was to evaluate the effect of different doses of Malaysian honey on male reproductive parameters in adult rats. Thirty-two healthy adult male Sprague-Dawley rats were randomly divided into four groups (eight rats per group). Group 1 (control group) was given 0.5 ml of distilled water. Groups 2, 3 and 4 were given 0.2, 1.2 and 2.4 g kg(-1) body weight of honey respectively. The rats were treated orally by gavage once daily for 4 weeks. Honey did not significantly alter body and male reproductive organs weights. The rats in Group 3 which received honey at 1.2 g kg(-1) had significantly higher epididymal sperm count than those in Groups 1, 2 and 4. No significant differences were found for the percentage of abnormal sperm, elongated spermatid count, reproductive hormonal levels as well as the histology of the testis among the groups. In conclusion, Malaysian honey at a dose of 1.2 g kg(-1) daily significantly increased epididymal sperm count without affecting spermatid count and reproductive hormones. These findings might suggest that oral administration of honey at this dose for 4 weeks may enhance spermiogenesis in adult rats.

  16. Mephedrone exposure in adolescent rats alters the rewarding effect of morphine in adults.

    PubMed

    Joanna, Listos; Sylwia, Talarek; Magdalena, Gryzinska; Piotr, Listos; Ewa, Kedzierska; Jolanta, Orzelska-Gorka; Malgorzata, Dylewska; Malgorzata, Lupina; Kotlinska, Jolanta H

    2017-09-05

    An increasing number of data show that exposure to mephedrone in adolescence can have long-lasting implication on brain activity and on peripheral organs/tissues. The aim of this study was to investigate whether adolescent exposure to mephedrone (10mg/kg, i.p.) has influence upon the rewarding effect of morphine (5mg/kg, i.p.) in adult rats. Thus, the adolescent rats (on the 30th PND) were treated with mephedrone for 7 consecutive days. When the animals were adult (on the 60th PND) the morphine-induced conditioned place preference (CPP) test was performed. After that, the level of DNA methylation in the striatum was investigated. DNA methylation is one of the epigenetic mechanisms which produces changes in the genome. These alterations may affect the phenotype, without effect on DNA sequences, and has influence on drug addiction. Additionally, in order to check the toxic properties of mephedrone on the peripheral organs, the histopathological examination of kidney and liver was carried out. The present experiments demonstrated that: 1) adolescent mephedrone exposure may intensify the rewarding effect of morphine in adult rats in the CPP test; 2) mephedrone may induce the alterations in DNA methylation in striatum of adult rats leading to changes in gene activity; 3) mephedrone may produce some retrogressive disturbances in kidney and liver, which confirms the toxic properties of this substance. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Histological effects of chronic consumption of soda pop drinks on kidney of adult Wister rats.

    PubMed

    Adjene, Josiah Obaghwarhievwo; Ezeoke, Joseph Chigozie; Nwose, Ezekiel Uba

    2010-05-01

    Health concerns over soda pop drinks have been severally report. However, histological perspectives are not very common. The objective of this study is to investigate histological effect of chronic consumption of soda pop drinks on the kidney of adult Wistar rats. The rats of both sexes (n = 24), with average weight of 200g were randomly assigned into two treatment (A & B) (n=16) and Control (c) (n=8) groups. The rats in the treatment group (A) received a brand of soda pop drink on a daily basis for thirty days. The rats in treatment group (B) received another brand of soda drink, while the control group (C) received equal amount of water for the same period. The rats were given the drinks as well as feeds liberally for thirty days, and sacrificed by cervical dislocation on the thirty-first day of the experiment. The kidney was carefully dissected out and quickly fixed in 10% formal saline for histological study. The findings indicate that rats in the treated groups (A&B) showed some varying degree of distortion and disruption of the renal structure. There are observable diffuse signs of glomerulonephritis with some congestion and tubular necrosis as compared to the control group. Chronic consumption of soda pop drinks may affect the microanatomy of the kidney of adult Wistar rats. Further study aimed at corroborating these observations in humans is warranted.

  18. Rapid neurobehavioral analysis of Pfiesteria piscicida effects in juvenile and adult rats.

    PubMed

    Levin, E D; Rezvani, A H; Christopher, N C; Glasgow, H B; Deamer-Melia, N J; Burkholder, J M; Moser, V C; Jensen, K

    2000-01-01

    The estuarine dinoflagellate Pfiesteria piscicida is known to kill fish and has been associated with neurocognitive deficits in humans. We have developed a rat model to demonstrate that exposure to Pfiesteria causes significant learning impairments. This has been repeatedly seen as a choice accuracy impairment during radial-arm maze learning. Pfiesteria-induced effects were also seen in a locomotor activity test in the figure-8 apparatus. The current studies used the short-term radial-arm maze acquisition, the figure-8 activity test, and the functional observational battery (FOB) to assess Pfiesteria-induced neurobehavioral effects in adult and juvenile rats. In study 1, the neurobehavioral potency of three different Pfiesteria cultures (Pf 113, Pf 728, and Pf Vandermere) was assessed. Ninety-six (12 per group) adult female Sprague-Dawley rats were injected subcutaneously with a single dose of Pfiesteria taken from aquarium-cultured Pfiesteria (35,600 or 106,800 Pfiesteria cells per kilogram of rat body weight). One control group (N = 12) was injected with saline and one (N = 12) with aquarium water not containing Pfiesteria. All three of the Pfiesteria samples (p < 0.05) impaired choice accuracy over the first six sessions of training. At the time of the radial-arm maze choice accuracy impairment, no overt Pfiesteria-related effects were seen using an FOB, indicating that the Pfiesteria-induced choice accuracy deficit was not due to generalized debilitation. In the figure-8 apparatus, Pfiesteria treatment caused a significant decrease in mean locomotor activity. In study 2, the neurobehavioral effects of the Pf 728 sample type were assessed in juvenile rats. Twenty-four day-old male and female rats were injected with 35,600 or 106,800 Pf-728 Pfiesteria cells per kilogram of rat body weight. As with adult females, the juvenile rats showed a significant impairment in radial-arm maze choice accuracy. No changes in locomotor activity or the FOB were detected in the

  19. Effect of acute ethanol and acute allopregnanolone on spatial memory in adolescent and adult rats.

    PubMed

    Chin, Vivien S; Van Skike, Candice E; Berry, Raymond B; Kirk, Roger E; Diaz-Granados, Jamie; Matthews, Douglas B

    2011-08-01

    The effects of ethanol differ in adolescent and adult rats on a number of measures. The evidence of the effects of ethanol on spatial memory in adolescents and adults is equivocal. Whether adolescents are more or less sensitive to ethanol-induced impairment of spatial memory acquisition remains unclear; with regard to the effects of acute ethanol on spatial memory retrieval there is almost no research looking into any age difference. Thus, we examined the effects of acute ethanol on spatial memory in the Morris Watermaze in adolescents and adults. Allopregnanolone (ALLO) is a modulator of the GABA(A) receptor and has similar behavioral effects as ethanol. We sought to also determine the effects of allopreganolone on spatial memory in adolescent and adults. Male adolescent (post natal [PN]28-30) and adult (PN70-72) rats were trained in the Morris Watermaze for 6 days and acute doses of ethanol (saline, 1.5 and 2.0 g/kg) or ALLO (vehicle, 9 and 18 mg/kg) were administered on Day 7. A probe trial followed on Day 8. As expected, there were dose effects; higher doses of both ethanol and ALLO impaired spatial memory. However, in both the ethanol and ALLO conditions adolescents and adults had similar spatial memory impairments. The current results suggest that ethanol and ALLO both impair hippocampal-dependent spatial memory regardless of age in that once learning has occurred, ethanol or ALLO does not differentially impair the retrieval of spatial memory in adolescents and adults. Given the mixed results on the effect of ethanol on cognition in adolescent rats, additional research is needed to ascertain the factors critical for the reported differential results.

  20. The effect of prenatal methamphetamine exposure on recognition memory in adult rats.

    PubMed

    Fialová, Markéta; Šírová, Jana; Bubeníková-Valešová, Věra; Šlamberová, Romana

    2015-01-01

    The use of methamphetamine (MA) among pregnant women is an increasing world-wide health problem. Prenatal MA exposure may cause changes in foetus but the exact effects have remained unclear. The aim of this study is to present the effect of prenatal MA exposure on recognition memory in adult rats. Adult female Wistar rats were injected daily with D-methamphetamine HCl (MA; 5 mg/kg, s.c.) during the entire gestation period. Control females were treated with saline in the same regime. Adult male offspring was administrated acutely by MA (1 mg/kg i.p.) or saline 30 minutes before beginning of an experiment. For testing recognition memory two tasks were chosen: Novel Object Recognition Test (NORT) and Object Location Test (OLT). Our results demonstrate that prenatally MA-exposed animals were worse in NORT independently on an acute administration of MA in adulthood. Prenatally MA-exposed rats did not deteriorate in OLT, but after acute administration of MA in adulthood, there was significant worsening compared to appropriate control. Prenatally saline-exposed offspring did not deteriorate in any test even after acute administration of MA. Our data suggest that prenatal MA exposure in rats cause impairment in recognition memory in adult offspring, but not in spatial memory. In addition, acute administration of MA to controls did not deteriorate either recognition or spatial memory.

  1. Lipid metabolism in ethanol-treated rat pups and adults: effects of folic Acid.

    PubMed

    Ojeda, Ma Luisa; Delgado-Villa, Ma Jesús; Llopis, Ruth; Murillo, Ma Luisa; Carreras, Olimpia

    2008-01-01

    In this study we determined whether a folic acid-supplemented diet could change hyperlipaemia provoked by chronic ethanol intake in adult and pup rats. Animals were randomized into eight groups (four adults and four pups): control groups, water and basic diet; alcohol groups, 20% ethanol and basic diet; alcohol folic acid groups, 20% ethanol and diet supplemented with folic acid; control folic acid groups, water and folic acid-supplemented diet. We determined serum and liver total cholesterol (Chol), HDL, triglycerides (TG), phospholipids (PL) and bile acids (BA) levels in all of the groups. Hydroxymethylglutaryl-CoA (HMG-CoA) reductase activity was also measured in the livers. Ethanol-fed rats have higher serum HDL and PL levels in pups and higher serum LDL, TG and PL levels in adults than controls and supplemented animals with or without alcohol ingestion. Ethanol provokes an increase in hepatic Chol and BA, and a decrease in hepatic TG and PL in pups; in adults it also provokes an increase in hepatic Chol and BA and a significant increase in HMG-CoA reductase activity. Alcohol intake plus folic acid supplementation has no effects on these values except BA levels that were significantly higher, in both pups and adult rats, than in the control group. Despite the fact that alcohol intake provokes different lipid alterations in adults and in pups whose mothers drank ethanol, folic acid contributes to the alleviation of these adverse effects reducing HMG-CoA reductase activity in adult rats and, except BA levels, to normalizing lipids values due to the fact that folic acid acts as a choleretic compound. We can therefore assume that folic acid supplementation reduces alcohol-induced hypercholesterolaemia by decreasing synthesis and increasing catabolism.

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

    PubMed

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

    2012-03-14

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

  3. Effect of simulated weightlessness on osteoprogenitor cell number and proliferation in young and adult rats.

    PubMed

    Basso, N; Bellows, C G; Heersche, J N M

    2005-01-01

    Experiments with rats flown in space or hind limb unloaded (HU) indicate that bone loss in both conditions is associated with a decrease in bone volume and osteoblast surface in cancellous and cortical bone. We hypothesize that the decrease in osteoblastic bone formation and osteoblast surface is related to a decrease in the number of osteoprogenitors and/or decreased proliferation of their progeny. We tested this hypothesis by evaluating the effect of 14 days of HU on the number of osteoprogenitors (osteoblast colony forming units; CFU-O), fibroblastic colony forming units (CFU-F), and alkaline phosphatase-positive CFU (CFU-AP) in cell populations derived from the proximal femur (unloaded) and the proximal humerus (normally loaded) in 6-week-old and 6-month-old rats. To confirm the effect of unloading on bone volume and structure, static histomorphometric parameters were measured in the proximal tibial metaphysis. Effects of HU on proliferation of osteoprogenitors were evaluated by measuring the size of CFU-O. HU did not affect the total number of progenitors (CFU-F) in young or adult rats in any of the cell populations. In femoral populations of young rats, HU decreased CFU-O by 71.0% and mean colony size was reduced by 20%. HU decreased CFU-AP by 31.3%. As expected, no changes in CFU-O or CFU-AP were seen in cell populations from the humerus. In femoral cell populations of adult rats, HU decreased CFU-O and CFU-AP by 16.6% and 36.6%, respectively. Again, no effects were seen in cell populations from the humerus. In 6-week-old rats, there was a greater decrease in bone volume, osteoblast number, and osteoblast surface in the proximal tibial metaphysis than that observed in adult rats. Both trabecular thickness and trabecular number were decreased in young rats but remained unaffected in adults. Neither osteoclast number nor surface was affected by unloading. Our results show that the HU-induced decrease in the number of osteoprogenitors observed in vitro

  4. Effect of seven days of spaceflight on hindlimb muscle protein, RNA and DNA in adult rats

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1985-01-01

    Effects of seven days of spaceflight on skeletal muscle (soleus, gastrocnemius, EDL) content of protein, RNA and DNA were determined in adult rats. Whereas total protein contents were reduced in parallel with muscle weights, myofibrillar protein appeared to be more affected. There were no significant changes in absolute DNA contents, but a significant (P less than 0.05) increase in DNA concentration (microgram/milligram) in soleus muscles from flight rats. Absolute RNA contents were significantly (P less than 0.025) decreased in the soleus and gastrocnemius muscles of flight rats, with RNA concentrations reduced 15-30 percent. These results agree with previous ground-based observations on the suspended rat with unloaded hindlimbs and support continued use of this model.

  5. Effect of seven days of spaceflight on hindlimb muscle protein, RNA and DNA in adult rats

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1985-01-01

    Effects of seven days of spaceflight on skeletal muscle (soleus, gastrocnemius, EDL) content of protein, RNA and DNA were determined in adult rats. Whereas total protein contents were reduced in parallel with muscle weights, myofibrillar protein appeared to be more affected. There were no significant changes in absolute DNA contents, but a significant (P less than 0.05) increase in DNA concentration (microgram/milligram) in soleus muscles from flight rats. Absolute RNA contents were significantly (P less than 0.025) decreased in the soleus and gastrocnemius muscles of flight rats, with RNA concentrations reduced 15-30 percent. These results agree with previous ground-based observations on the suspended rat with unloaded hindlimbs and support continued use of this model.

  6. Malnutrition during brain growth spurt alters the effect of fluoxetine on aggressive behavior in adult rats.

    PubMed

    Barreto-Medeiros, J M; Feitoza, E G; Magalhaes, K; Cabral-Filho, J E; Manhaes-De-Castro, F M; De-Castro, C M; Manhaes-De-Castro, R

    2004-02-01

    Malnutrition effect during the suckling period on aggressive behavior was investigated in adult rats treated and not treated with fluoxetine, a selective serotonin reuptake inhibitor. Sixty-four Wistar male rats were allocated in two groups, according to their mothers' diet during lactation. The well-nourished group was fed by mothers receiving a 23% protein diet; the malnourished one by mothers receiving a 8% protein diet. Following weaning, all rats received the 23% protein diet. On the 90th day after birth, each nutritional group was divided into two subgroups, one receiving a single daily injection of fluoxetine (10 mg/kg) and the other of a saline solution (0.9% NaCl) for 14 days. Treatment with Fluoxetine reduced aggressive response in well-nourished but not in malnourished rats. These findings suggest that the serotoninergic system was affected by malnutrition during the critical period of brain development, and persisted even after a long period of nutritional recovery.

  7. Nicotine withdrawal in adolescent and adult rats.

    PubMed

    O'Dell, Laura E; Bruijnzeel, Adrie W; Ghozland, Sandy; Markou, Athina; Koob, George F

    2004-06-01

    Previous research with animal models has demonstrated that adolescent rats display heightened sensitivity to the reinforcing and stimulant effects of nicotine relative to adult rats. Little work has focused on the response of adolescent rats to measures of nicotine withdrawal. To test the hypothesis that adolescent rats may be differentially sensitive to withdrawal relative to their adult counterparts, the present study was designed to compare precipitated withdrawal in adolescent and adult rats following chronic nicotine administration. Adult and adolescent rats were prepared with subcutaneous osmotic minipumps that delivered either saline or nicotine (9 mg/kg per day, salt; N =12 per group). All rats were challenged with the nicotinic receptor antagonist mecamylamine (1.5 mg/kg) on day 7 of chronic nicotine treatment. Twenty minutes after the injection, overt somatic signs of withdrawal (i.e., eye blinks, writhes, body shakes, teeth chatter, gasps, and ptosis) were recorded for 10 min. Adult rats were observed on postnatal day 73-77, and adolescent rats were tested on postnatal day 36-40. The results revealed a robust increase in mecamylamine-induced withdrawal signs in adult rats receiving chronic nicotine relative to adult rats receiving saline. In contrast, mecamylamine did not precipitate withdrawal signs in adolescent rats receiving chronic nicotine. These results indicate that there is decreased sensitivity to the somatic aspects of nicotine withdrawal in adolescent rats that may maximize the reinforcing effects of nicotine during adolescence by minimizing the aversive effects of abstinence.

  8. Effect of morphine, naloxone and histamine system on water intake in adult male rats.

    PubMed

    Eidi, Maryam; Oryan, Shahrbanoo; Eidi, Akram; Sepehrara, Leili

    2003-10-08

    The present study investigated the interaction between histamine and opioid systems on water intake in adult male rats. Intracerebroventricular (i.c.v.) injections were carried out in all experiments. Water intake was measured 1 h after drug injections. Administration of histamine (40-80 microg/rat) and naloxone (0.5-1 microg/rat) increased, while morphine (2.5 microg/rat), pyrilamine (25-50 microg/rat), the histamine H1 receptor antagonist, and ranitidine (10-20 microg/rat), the histamine H2 receptor antagonist, decreased water intake in isolated rats. Blockade of histamine H1 and H2 receptors attenuated the histamine-induced response. Pyrilamine, but not ranitidine, increased the inhibitory effect induced by morphine. Also, pharmacological blockade of histamine H1 and H2 receptors decreased the naloxone-induced effect on water intake. It is concluded that the histaminergic system may have a close interaction with morphine and naloxone on drinking behavior.

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

    PubMed Central

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

    2012-01-01

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

  10. Effect of food restriction on reproductive-related genes and reproductive hormones in adult female rats.

    PubMed

    Ahmed, H H; Khalil, W K B; Shousha, W G; El-Sayed, E S M; Eskander, E F; Selim, R E

    2012-11-01

    A number of factors involved in the control of energy balance and metabolism act as modulators of gonadal axis. Ghrelin, a peptide secreted from the stomach and hypothalamus, has emerged as an orexigenic food intake controlling signal acting upon hypothalamus. Recently, the potential reproductive role of ghrelin has received great attention. This study was designed to investigate the influence of food restriction and consequent metabolic hormone (ghrelin) on the level and gene expression of female reproductive hormones in adult rats. To study the effect of chronic food restriction on ghrelin level in adult female rats and its relation to female reproductive hormones, 32 adult female Sprague Dawley rats divided into 4 groups: Group I (control group) comprised 8 rats fed ad libitum for 30 days, Group II, III and IV (food-restricted groups for 10, 20 and 30 days respectively) each consisted of 8 rats fed 50% of ad libitum intake determined by the amount of food consumed by the control group. Mean body weight of food restricted rats was observed to decrease during the period of the experiment. Food restriction produced significant increase of serum ghrelin with significant decrease of both gastric and hypothalamic ghrelin accompanied with significant increase in its gene expression in stomach and hypothalamus. Estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels showed significant decrease correlated with down-regulation of gonadotropins, cyclin-dependent kinase (cdc2), cyclin B and kisspeptin (Kiss1) genes in food restricted rats compared with control group. Ghrelin could be one of the hormones responsible for the suppression of female reproductive axis in case of negative energy balance. Thus, ghrelin may operate as an autocrine/paracrine regulator of ovarian function. Overall, ghrelin may represent an additional link between body weight homeostasis and reproductive function.

  11. Decreased Sensitivity in Adolescent versus Adult Rats to the Locomotor Activating Effects of Toluene

    PubMed Central

    Bowen, Scott E.; Charlesworth, Jonathan D.; Tokarz, Mary E.; Jerry Wright, M.; Wiley, Jenny L.

    2007-01-01

    Volatile organic solvent (inhalant) abuse continues to be a major health concern throughout the world. Of particular concern is the abuse of inhalants by adolescents because of its toxicity and link to illicit drug use. Toluene, which is found in many products such as glues and household cleaners, is among the most commonly abused organic solvents. While studies have assessed outcomes of exposure to inhalants in adult male animals, there is little research on the neurobehavioral effects of inhalants in female or younger animals. In attempt to address these shortcomings, we exposed male and female Long-Evans rats to 20 min of 0, 2,000, 4,000, or 8,000 parts per million (ppm) inhaled toluene for 10 days in rats aged postnatal (PN) day 28-39 (adolescent), PN44-PN55, or >PN70 (adult). Animals were observed individually in 29-l transparent glass cylindrical jars equipped with standard photocells that were used to measure locomotor activity. Toluene significantly increased activity as compared to air exposure in all groups of male and female rats with the magnitude of locomotor stimulation produced by 4000 ppm toluene being significantly greater for female adults than during any age of adolescence. The results demonstrate that exposure to abuse patterns of high concentrations of toluene through inhalation can alter spontaneous locomotor behavior in rats and that the expression of these effects appears to depend upon the postnatal age of testing and sex of the animal. PMID:17869480

  12. Biochemical effect of a ketogenic diet on the brains of obese adult rats.

    PubMed

    Mohamed, Hoda E; El-Swefy, Sahar E; Rashed, Leila A; Abd El-Latif, Sally K

    2010-07-01

    Excess weight, particularly abdominal obesity, can cause or exacerbate cardiovascular and metabolic disease. Obesity is also a proven risk factor for Alzheimer's disease (AD). Various studies have demonstrated the beneficial effects of a ketogenic diet (KD) in weight reduction and in modifying the disease activity of neurodegenerative disorders, including AD. Therefore, in this study we examined the metabolic and neurodegenerative changes associated with obesity and the possible neuroprotective effects of a KD in obese adult rats. Compared with obese rats fed a control diet, obese rats fed a KD showed significant weight loss, improvement in lipid profiles and insulin resistance, and upregulation of adiponectin mRNA expression in adipose tissue. In addition, the KD triggered significant downregulation of brain amyloid protein precursor, apolipoprotein E and caspase-3 mRNA expression, and improvement of brain oxidative stress responses. These findings suggest that a KD has anti-obesity and neuroprotective effects.

  13. Effect of prenatal exposure to waterpipe tobacco smoke on learning and memory of adult offspring rats.

    PubMed

    Al-Sawalha, Nour; Alzoubi, Karem; Khabour, Omar; Alyacoub, Weam; Almahmmod, Yehya; Eissenberg, Thomas

    2017-06-20

    Waterpipe tobacco smoking has increased in prevalence worldwide, including among pregnant women. In this study, we investigated the effect of prenatal maternal waterpipe tobacco smoke (WTS) exposure during different stages of pregnancy on learning and memory of adult offspring rats. Pregnant rats received either fresh air or mainstream WTS (two hours daily) during early, mid, late, or whole gestational period. Male offspring rats were followed through 20 weeks. Outcomes included 1) spatial learning and memory using the radial arm water maze (RAWM), 2) levels of brain derived neurotrophic factor (BDNF) in the hippocampus, and 3) oxidative stress biomarkers (superoxide dismutase, catalase, glutathione peroxidase and thiobarbituric acid reactive substances). Relative to offspring whose mothers were exposed to fresh air, prenatal exposure to WTS at any stage of pregnancy resulted in short- and long-term memory impairment in adult offspring rats (P < 0.05). This impairment was associated with reduced levels of BDNF in hippocampus (P < 0.05). However, prenatal WTS did not affect the level of oxidative stress biomarkers in hippocampus. Prenatal WTS during late gestation increased the activity of catalase as compared to control. Prenatal maternal WTS exposure can impair the memory of adult male offspring. These results support development of interventions that target pregnant women who smoke waterpipe during pregnancy. We examined for the first time the effect of prenatal waterpipe tobacco smoke exposure on learning and memory of offspring. The results showed that in utero exposure to waterpipe tobacco smoke was associated with impaired memory and decreased brain derived neurotrophic factor in hippocampus of adult male offspring rats.

  14. Effect of medroxyprogesterone acetate on thyrotropin secretion in adult and old female rats.

    PubMed

    Moreira, R M; Borges, P P; Lisboa, P C; Curty, F H; Moura, E G; Pazos-Moura, C C

    2000-09-01

    Steroid hormones have been implicated in the modulation of TSH secretion; however, there are few and controversial data regarding the effect of progesterone (Pg) on TSH secretion. Medroxyprogesterone acetate (MPA) is a synthetic alpha-hydroxyprogesterone analog that has been extensively employed in therapeutics for its Pg-like actions, but that also has some glucocorticoid and androgen activity. Both hormones have been shown to interfere with TSH secretion. The objective of the present study was to investigate the effects of MPA or Pg administration to ovariectomized (OVX) rats on in vivo and in vitro TSH release and pituitary TSH content. The treatment of adult OVX rats with MPA (0. 25 mg/100 g body weight, sc, daily for 9 days) induced a significant (P<0.05) increase in the pituitary TSH content, which was not observed when the same treatment was used with a 10 times higher MPA dose or with Pg doses similar to those of MPA. Serum TSH was similar for all groups. MPA administered to OVX rats at the lower dose also had a stimulatory effect on the in vitro basal and TRH-induced TSH release. The in vitro basal and TRH-stimulated TSH release was not significantly affected by Pg treatment. Conversely, MPA had no effect on old OVX rats. However, in these old rats, ovariectomy alone significantly reduced (P<0.05) basal and TRH-stimulated TSH release in vitro, as well as pituitary TSH content. The results suggest that in adult, but not in old OVX rats, MPA but not Pg has a stimulatory effect on TSH stores and on the response to TRH in vitro.

  15. Effects of cyclophosphamide on the kaolin consumption (pica behavior) in five strains of adult male rats.

    PubMed

    Tohei, Atsushi; Kojima, Shu-ichi; Ikeda, Masashi; Hokao, Ryoji; Shinoda, Motoo

    2011-07-01

    It is known that pica, the consumption of non-nutritive substances such as kaolin, can be induced by administration of toxins or emetic agents in rats. In the present study, we examined the effects of intraperitoneal (i.p.) administration of cyclophosphamide on pica behavior and on the concentration of 5-hydroxyindoleacetic acids (5HIAA) in cerebrospinal fluid (CSF) in the following five strains of adult male rats: Sprague Dawley (SD), Wistar, Fischer 344 (F344), Wistar-Imamichi (WI) and Long Evans (LE). Cyclophosphamide (25 mg or 50 mg/kg) was injected (i.p.) into the rats and kaolin and food intake were measured at 24 hr after injection. The animals were anesthetized with urethane (1 g/kg) at 3 hr after injection of cyclophosphamide, and CSF was collected from the cisterna magna. WI and LE rats clearly showed pica behavior as compared with the other strains. In LE rats, the concentration of 5HIAA in CSF also increased in a dose-dependent manner of cyclophosphamide. The pretreatment with ondansetron (5-HT(3) antagonist) restored both changes (kaolin consumption and 5HIAA levels) induced by cyclophosphamide. These results suggest that the LE rat is sensitive to cyclophosphamide, that pica induced by cyclophosphamide mimics many aspects of emesis including the serotonergic response in the central nervous system and that use of the pica model would be a practical method for evaluating the effects of antiemetic drugs in addition to the mechanism of emesis.

  16. Effect of the antioxidant dibunol on adrenocortical, thyroid, and adenohypopyseal function in adult and old rats

    SciTech Connect

    Gorban', E.N.

    1986-04-01

    This paper studies the effect of dibunol (4-methyl-2,6-di-tert-butylphenol) (D) on the function of the adrenal cortex, thyroid gland, and adenhypophysis, which produces trophic hormones for the other two glands. Experiments were carried out on adult rats. After injection of D concentrations of corticosterone (CS), triodothyronine (T/sub 3/), ACTH, and thyrotrophin (TSH) in the blood plasma and the CS concentration in tssue of the adenohypophysis were determined. It is shown that injection of D caused biphasic changes in the CS concentration in both tissues studied in adult and old animals.

  17. Effects of desipramine and alprazolam on forced swimming behaviour of adult rats exposed to prenatal diazepam.

    PubMed

    Cannizzaro, C; Cannizzaro, E; Gagliano, M; Mineo, A; Sabatino, M; Cannizzaro, G

    1995-02-06

    Pregnant rats were treated with a single daily s.c. injection of diazepam (2 mg/kg) over gestation days 14-20. This treatment led to a reduction in GABA receptor complex function since adult male offspring showed a strong decrease in electrographic hippocampal responses to alprazolam and a strongly increased response to picrotoxin after intra-locus coeruleus injection of the two compounds. No difference in immobility time in the forced swimming test and in spontaneous motor activity was observed between prenatally vehicle- and diazepam-exposed offspring. Conversely, prenatal exposure to diazepam potentiated the anti-immobility effect of subchronic desipramine (10 mg/kg i.p.) and made active a dose of desipramine (5 mg/kg i.p.) that was ineffective in prenatally vehicle-exposed rats. This effect was observed only in pretested rats. Prenatal exposure to diazepam blocked the anti-immobility effect of subchronic alprazolam (15 mg/kg i.p.) in both non-pretested and pretested rats. Spontaneous motor activity was strongly reduced in all groups. These findings suggest that a persistent reduction in GABA receptor complex function, induced by prenatal exposure to diazepam, does not alter the mobility of adult progeny in the forced swimming test, but it may have consequences when drugs acting on the GABA receptor complex are used.

  18. Lateralized effects of monocular training on dendritic branching in adult split-brain rats.

    PubMed

    Chang, F L; Greenough, W T

    1982-01-28

    A number of experimental approaches have indicated differential interneuronal connectivity following differential experience during both development and adulthood. In Golgi preparations, prolonged maze training was reported to alter dendritic branching of distal apical dendrites of Layer IV and V pyramidal neurons in adult rat occipital cortex. To determine the specificity of this effect to direct involvement in the visual aspects of training, the effects of monocular maze training, using a split-brain procedure and opaque contact occluders, was examined in the present study. Rats were maze trained with unilateral or alternating monocular occlusion, while nontrained rats with unilateral or alternating monocular occlusion were handled briefly and given water reward. There was no within-animal effect of fixed occluder position in non-trained controls. In unilaterally-occluded trained rats, Layer V pyramidal neurons in occipital cortex opposite the open eye had greater oblique dendritic length in the distal region of the apical dendrite than did those opposite the occluded eye. Similarly, rats trained with alternating occlusion had greater distal apical oblique dendritic length in Layer V occipital pyramidal neurons than did nontrained controls. This indicates that morphological sequelae of training are concentrated in areas processing information associated with visual aspects of the training and renders unlikely general metabolic or hormonal causation of such effects.

  19. Effect of amphetamine on adult male and female rats prenatally exposed to methamphetamine.

    PubMed

    Šlamberová, Romana; Macúchová, Eva; Nohejlová, Kateryna; Štofková, Andrea; Jurčovičová, Jana

    2014-01-01

    The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to adult amphetamine (AMP) treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed) were administered with AMP (5 mg/kg) or saline (1 ml/kg) in adulthood. Behaviour in unknown environment was examined in open field test (Laboras), active drug-seeking behaviour in conditioned place preference test (CPP), spatial memory in the Morris water maze (MWM), and levels of corticosterone (CORT) were analyzed by enzyme immunoassay (EIA). Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled) regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing) only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.

  20. Histological effects of oral administration of nutmeg on the kidneys of adult Wister rats

    PubMed Central

    Eweka, Andrew Osayame; Eweka, Abieyuwa

    2010-01-01

    Aims: The effects of oral administration of nutmeg commonly used as spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the kidneys of adult Wistar rats were carefully studied. Material and Methods: Rats of both sexes (n = 24), with average weight of 220g were randomly assigned into two treatments (A & B) of (n=16) and Control (c) (n=8) groups. The rats in the treatment groups (A & B) received 0.1g (500mg/kg body weight) and 0.2g (1000mg/kg body weight) of nutmeg thoroughly mixed with the feeds respectively on a daily basis for forty-two days. The control group (c) received equal amount of feeds daily without nutmeg added for forty-two days. The growers’ mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo state, Nigeria and the rats were given water liberally. The rats were sacrificed by cervical dislocation on the forty-third day of the experiment. The kidneys were carefully dissected out and quickly fixed in 10% buffered formaldehyde for routine histological study after hematoxylin and eosin method. Result: The histological findings in the treated sections of the kidneys showed distortion of the renal cortical structures, vacuolations appearing in the stroma and some degree of cellular necrosis, with degenerative and atrophic changes when compared to the control group. Conclusion: These findings indicate that oral administration of nutmeg may have some deleterious effects on the kidneys of adult Wistar rats at higher doses and by extension may affect its excretory and other metabolic functions. It is recommended that caution should therefore be advocated in the intake of this product and further studies be carried out to examine these findings. PMID:22624138

  1. Behavorial effects of subchronic inhalation of toluene in adult rats

    EPA Science Inventory

    Whereas the acute neurobehavioral effects oftoluene are robust and well characterized, evidence for persistent effects ofrepeated exposure to this industrial solvent is less compelling. The present studies sought to determine whether repeated inhalation oftoluene caused persist...

  2. Behavorial effects of subchronic inhalation of toluene in adult rats

    EPA Science Inventory

    Whereas the acute neurobehavioral effects oftoluene are robust and well characterized, evidence for persistent effects ofrepeated exposure to this industrial solvent is less compelling. The present studies sought to determine whether repeated inhalation oftoluene caused persist...

  3. On Again, Off Again Effects of Gonadectomy on the Acoustic Startle Reflex in Adult Male Rats

    PubMed Central

    Turvin, J.C.; Messer, W.S.

    2007-01-01

    Numerous studies have shown sex and/or estrous cycle differences in the acoustic startle reflex (ASR) and its prepulse inhibition (PPI) in humans and animals. However, few have examined the effects of hormone manipulations on these behaviors. This study paired gonadectomy (GDX) in adult male rats with testing for ASR and PPI at 2, 4, 9, 16, 23, 30 and 37 days after surgery. Initial studies of control, GDX and GDX rats given testosterone propionate revealed no group differences in PPI, but did reveal phasic facilitation of the ASR in GDX rats that was greatest on the first and final testing sessions and that was attenuated by testosterone. A second study addressing roles for estrogen and androgen signaling tested new control and GDX rats along with GDX rats given estradiol or the non-aromatizable androgen, 5-alpha-dihydrotestosterone and revealed no group differences in PPI, and increases in ASR in GDX rats that were largest during the first and final testing sessions and that were attenuated by both hormone replacements. However, while responses in GDX rats given testosterone were similar to those of controls, ASR in estradiol- and to a lesser extent in dihydrotestosterone-treated GDX rats were typically lower than in controls. This may suggest that hormone modulation of the ASR requires synergistic estrogen and androgen actions. In the male brain where this can be achieved by local steroid metabolism, the enzymes responsible, e.g., aromatase, could help identify loci in the startle circuitry that may be especially relevant for the hormone modulation observed. PMID:17169383

  4. Effect of restraint and copper deficiency on blood pressure and mortality of adult rats

    SciTech Connect

    Klevay, L.M.; Halas, E.S. )

    1989-02-01

    The etiology of most hypertension is unknown; stress is thought to elevate blood pressure. Male, weanling Sprague-Dawley rats were fed a purified diet plus a drinking solution containing 10{mu}g Zn and 2{mu}g Cu/ml (acetate sulfate, respectively). Systolic blood pressure was measured without anesthesia. After being matched by mean weight (280g) and blood pressure into 4 groups of 15, groups 1 and 2 received a drinking solution without copper. After 24 days rats in groups 2 and 4 were restrained for 45 min. daily (A.M.) for 23 days in a small plastic cage (19{times}6{times}6 cm). Final pressures were affected both by stress and dietary Cu: group 1, 119; group 2, 131; group 3, 114; group 4, 123 mm Hg. One rat in each of groups 1, 3, 4 and 10 rats in group 2, died. Among these latter hemorrhage was prominent, blood being found in bladder (2), gut (2), peritoneum (2) and scrotum (1). Copper deficiency decreased cooper in both adrenal gland and liver by 58% and in heart by 29% restraint was without effect. Cardiac sodium was increased 6% only by deficiency. Results confirm the hypertensive effect of copper deficiency in adult rats and reveal that the stress of restraint increases blood pressure. Copper deficiency plus stress is harmful.

  5. Perfluorooctane sulfonate effects on the reproductive axis in adult male rats.

    PubMed

    López-Doval, S; Salgado, R; Pereiro, N; Moyano, R; Lafuente, A

    2014-10-01

    Perfluorooctane sulfonate (PFOS) is a neurotoxic agent and it can disrupt the endocrine system activity. This work was undertaken to evaluate the possible effects of PFOS exposure on the hypothalamic-pituitary-testicular axis (HPT) in adult male rats, and to evaluate the possible morphological alterations induced by PFOS in the endocrine tissues of this axis. Adult male rats were orally treated with 0.5; 1.0; 3.0 and 6.0 mg of PFOS/kg/day for 28 days. After PFOS exposure, hypothalamic noradrenaline concentration increased in the anterior hypothalamus and in the median eminence, not changing in the mediobasal hypothalamus. PFOS treated rats presented a decrease of the gonadotropin releasing hormone (GnRH) gene expression, increasing the mRNA levels of the luteinizing hormone (LH) in rats treated with all doses administered except with the dose of 6 mg/kg/day. PFOS also induced a raise of the follicle stimulating hormone (FSH) gene expression in the animals exposed to 0.5 and 1.0 mg of PFOS/kg/day. After PFOS exposure, hypothalamic GnRH concentration was modified, LH and testosterone release was inhibited and FSH secretion was stimulated. Moreover, PFOS induced several histopathological alterations in the hypothalamus, pituitary gland and testis. The results obtained in the present study suggest in general terms that PFOS can inhibit the physiological activity of the reproductive axis in adult male rats, which could be explained, at least in part, by the structural alterations showed in the animals exposed to this chemical: very dense chromatin, condensed ribosomes and a loss of the morphology in the hypothalamus; a degeneration of the gonadotrophic cells, as well as a loss and degeneration of the spermatozoids and a very marked edema in the testis.

  6. Stress, kappa manipulations, and aversive effects of ethanol in adolescent and adult male rats

    PubMed Central

    Anderson, Rachel I.; Agoglia, Abigail E.; Morales, Melissa; Varlinskaya, Elena I.; Spear, Linda P.

    2013-01-01

    Elevated ethanol use during adolescence, a potentially stressful developmental period, is accompanied by insensitivity to many aversive effects of ethanol relative to adults. Given evidence that supports a role for stress and the kappa opioid receptor (KOR) system in mediating aversive properties of ethanol and other drugs, the present study assessed the role of KOR antagonism by norbinaltorphimine (nor-BNI) on ethanol-induced conditioned taste aversion (CTA) in stressed (exposed to repeated restraint) and non-stressed male rats (Experiment 1), with half of the rats pretreated with nor-BNI before stressor exposure. In Experiment 2, CTA induced by the kappa agonist U62,066 was also compared in stressed and non-stressed adolescents and adults. A highly palatable solution (chocolate Boost) was used as the conditioned stimulus (CS), thereby avoiding the need for water deprivation to motivate consumption of the CS during conditioning. No effects of stress on ethanol-induced CTA were found, with all doses eliciting aversions in adolescents and adults in both stress conditions. However, among stressed subjects, adults given nor-BNI before the repeated stressor displayed blunted ethanol aversion relative to adults given saline at that time. This effect of nor-BNI was not seen in adolescents, findings that support a differential role for the KOR involvement in ethanol CTA in stressed adolescents and adults. Results from Experiment 2 revealed that all doses of U62,066 elicited aversions in non-stressed animals of both ages that were attenuated in stressed animals, findings that support a modulatory role for stress in aversive effects of KOR activation. Collectively, these results suggest that although KOR sensitivity appears to be reduced in stressed subjects, this receptor system does not appear to contribute to age differences in ethanol-induced CTA under the present test circumstances. PMID:23276674

  7. Effects of Estradiol and Methoxychlor on Leydig Cell Regeneration in the Adult Rat Testis

    PubMed Central

    Chen, Bingbing; Chen, Dongxin; Jiang, Zheli; Li, Jingyang; Liu, Shiwen; Dong, Yaoyao; Yao, Wenwen; Akingbemi, Benson; Ge, Renshan; Li, Xiaokun

    2014-01-01

    The objective of the present study is to determine whether methoxychlor (MXC) exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2). Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS) to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control), 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7–15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms. PMID:24806340

  8. Toluene effects on the motor activity of adolescent, young-adult, middle-age and senescent male Brown Norway rats.

    PubMed

    MacPhail, R C; Farmer, J D; Jarema, K A

    2012-01-01

    Life stage is an important risk factor for toxicity. Children and aging adults, for example, are more susceptible to certain chemicals than are young adults. In comparison to children, relatively little is known about susceptibility in older adults. Additionally, few studies have compared toxicant susceptibility across a broad range of life stages. Results are presented for behavioral evaluations of male Brown Norway rats obtained as adolescents (1 month), or young (4 months), middle-age (12 months) and senescent (24 months) adults. Motor activity was evaluated in photocell devices during 30-min sessions. Age-related baseline characteristics and sensitivity to toluene (0, 300, 650, or 1000mg/kg, p.o.) were determined. In Experiment 1, young-adult, middle-age and senescent rats were treated with corn-oil vehicle before five weekly test sessions. Baselines of horizontal and vertical activity decreased with age, but each age-group's averages remained stable across weeks of testing. Baseline activity of older rats was more variable than that of the young adults; older rats were also more variable individually from week to week. Toluene (1000mg/kg) increased horizontal activity proportionately more in senescent rats (ca. 300% of control) than in middle-age or young-adult rats (ca.145-175% of control). Experiment 2 established toluene dose-effect functions in individual adolescent, young-adult, middle-age and senescent rats; each rat received all treatments, counterbalanced across four weekly sessions. Toluene produced dose-related increases in horizontal activity that increased proportionately with age. Experiment 3 replicated the effects of toluene (1000mg/kg) in Experiment 1, showing that toluene-induced increases in horizontal activity were greatest in the oldest rats. Collectively, the results show that aging increased susceptibility to toluene and also increased variability in toluene response. Given the rapid growth of the aged population, further research is

  9. Differential Effects of Inhaled Toluene on Locomotor Activity in Adolescent and Adult Rats

    PubMed Central

    Batis, Jeffery C.; Hannigan, John H.; Bowen, Scott E.

    2010-01-01

    Inhalant abuse is a world-wide public health concern among adolescents. Most preclinical studies have assessed inhalant effects in adult animals leaving unclear how behavioral effects differ in younger animals. We exposed adolescent (postnatal day [PN] 28) and adult (PN90) male rats to toluene using 1 of 3 exposure patterns. These patterns modeled those reported in toluene abuse in teens and varied concentration, number and length of exposures, as well as the inter-exposure interval. Animals were exposed repeatedly over 12 days to toluene concentrations of 0, 8,000 or 16,000 parts per million (ppm). Locomotor activity was quantified during toluene exposures and for 30 min following completion of the final daily toluene exposure. For each exposure pattern, there were significant toluene concentration-related increases and decreases in locomotor activity compared to the 0-ppm “air” controls at both ages. These changes depended upon when activity was measured – during or following exposure. Compared to adults, adolescents displayed greater locomotor activity on the first day and generally greater increases in activity over days than adults during toluene exposure. Adults displayed greater locomotor activity than adolescents in the “recovery” period following exposure on the first and subsequent days. Age group differences were clearest following the pattern of paced, brief (5-min) repeated binge exposures. The results suggest that locomotor behavior in rats during and following inhalation of high concentrations of toluene depends on age and the pattern of exposure. The results are consistent with dose-dependent shifts in sensitivity and sensitization or tolerance to repeated toluene in the adolescent animals compared to the adult animals. Alternate interpretations are possible and our interpretation is limited by the range of very high concentrations of toluene used. The results imply that both pharmacological and psychosocial factors contribute to the teen

  10. Environmental and tactile stimulation modulates the neonatal handling effect on adult rat spatial memory.

    PubMed

    Daskalakis, Nikolaos P; Kaperoni, Maria; Koros, Christos; de Kloet, E Ronald; Kitraki, Efthimia

    2009-12-01

    Handling of rat pups promotes their adult cognitive performance. However, new data suggest that individual components of the handling procedure, like exposure to novelty or tactile stimulation, have distinct lasting effects on behaviour. In this study we examined the interaction of early novelty exposure with a varying amount of tactile stimulation on spatial recognition memory and corticosterone secretion of adult male and female rats. A split litter design was used and the experimental animals were also compared to animal facility reared controls. The experiment was conducted in two phases. In the first phase, we examined the effect of novel or home environment during the 15-min of neonatal handling, following 10 back-strokes. Tactile stimulation of 10 back-strokes combined with novelty exposure, enhanced novel arm discrimination in a Y-maze task in adult rats of both sexes compared to their siblings that stayed at home, as well as to the animal facility reared controls. In the second phase, additional back-stroking (total of 20 back-strokes) reduced the Y-maze performance of males neonatally exposed to novelty, while the same treatment enhanced the performance of their siblings that stayed at home. Basal corticosterone levels, determined 1 week post-Y-maze, were significantly increased only in the novelty exposed/10 back-stroked females compared to same sex non-handled controls. In contrast, 10 back-strokes combined with the home cage environment increased corticosterone in males. Increase to 20 back-strokes reversed the impact of neonatal environment on corticosterone levels. These data suggest that the nature and intensity of the individual components of a mild early life manipulation, like handling, are critical in modifying aspects of adult memory performance and basal adrenocortical function.

  11. Effect of methamphetamine on cognitive functions of adult female rats prenatally exposed to the same drug.

    PubMed

    Macúchová, E; Nohejlová-Deykun, K; Slamberová, R

    2013-01-01

    The aim of this study was to investigate the effect of prenatal methamphetamine (MA) exposure and application of the same drug in adulthood on cognitive functions of adult female rats. Animals were prenatally exposed to MA (5 mg/kg) or saline (control group). The cognitive function was tested as ability of spatial learning in the Morris Water Maze (MWM). Each day of the experiment animals received an injection of MA (1 mg/kg) or saline. Our results demonstrated that prenatal MA exposure did not affect the latency to reach the hidden platform or the distance traveled during the Place Navigation Test; however, the speed of swimming was increased in prenatally MA-exposed rats compared to controls regardless of the treatment in adulthood. MA treatment in adulthood increased the latency and distance when compared to controls regardless of the prenatal exposure. Neither prenatal exposure, nor treatment in adulthood affected memory retrieval. As far as the estrous cycle is concerned, our results showed that prenatally MA-exposed females in proestrus/estrus swam faster than females in diestrus. This effect of estrous cycle was not apparent in control females. In conclusion, our results indicate that postnatal, but not prenatal exposure to MA affects learning of adult female rats.

  12. Environmental enrichment for adult rats: effects on trait and state anxiety.

    PubMed

    Goes, Tiago Costa; Antunes, Fabrício Dias; Teixeira-Silva, Flavia

    2015-01-01

    Experimental evidence indicates that enriched environment (EE) induces neurobiological and behavioural alterations. EE in early life improves learning and memory and reduces trait and state anxiety. However, the effect of EE established in adulthood has rarely been investigated. Thus, the aim of this study was to evaluate the possibility of modifying the levels of trait and/or state anxiety of adult rats exposed to EE. Seventy adult Wistar male rats were first tested in the free-exploratory paradigm (FEP) and were categorized according to their levels of trait anxiety (high, medium and low). Subsequently, half of the animals from each category returned to their home cages (standard condition: SC) and the other half was transferred to an enriched environment (enriched condition: EC). After three weeks, all animals were again tested in FEP. Seven to 10 days later, fifty of the seventy animals were tested on the elevated plus-maze test (EPM). In FEP, EE reduced locomotor activity in the second exposition independently of the anxiety category and, it decreased the levels of trait anxiety of highly anxious rats. No effect of EE was observed on EPM. In conclusion, EE established in adulthood was able to reduce high trait anxiety, a major risk factor for anxiety disorders. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Neonatal hyperleptinaemia programmes adrenal medullary function in adult rats: effects on cardiovascular parameters.

    PubMed

    Trevenzoli, I H; Valle, M M R; Machado, F B; Garcia, R M G; Passos, M C F; Lisboa, P C; Moura, E G

    2007-04-15

    Epidemiological studies have shown a strong correlation between stressful events (nutritional, hormonal or environmental) in early life and development of adult diseases such as obesity, diabetes and cardiovascular failure. It is known that gestation and lactation are crucial periods for healthy growth in mammals and that the sympathoadrenal system is markedly influenced by environmental conditions during these periods. We previously demonstrated that neonatal hyperleptinaemia in rats programmes higher body weight, higher food intake and hypothalamic leptin resistance in adulthood. Using this model of programming, we investigated adrenal medullary function and effects on cardiovascular parameters in male rats in adulthood. Leptin treatment during the first 10 days of lactation (8 microg 100 g(-1) day(-1), s.c.) resulted in lower body weight (6.5%, P < 0.05), hyperleptinaemia (10-fold, P < 0.05) and higher catecholamine content in adrenal glands (18.5%, P < 0.05) on the last day of treatment. In adulthood (150 days), the rats presented higher body weight (5%, P < 0.05), adrenal catecholamine content (3-fold, P < 0.05), tyrosine hydroxylase expression (35%, P < 0.05) and basal and caffeine-stimulated catecholamine release (53% and 100%, respectively, P < 0.05). Systolic blood pressure and heart rate were also higher in adult rats (7% and 6%, respectively, P < 0.05). Our results show that hyperleptinaemia in early life increases adrenal medullary function in adulthood and that this may alter cardiovascular parameters. Thus, we suggest that imprinting factors which increase leptin and catecholamine levels during the neonatal period could be involved in development of adult chronic diseases.

  14. Effects of thyroidectomy or thiouracil treatment on copulatory behavior in adult male rats.

    PubMed

    Tohei, A; Watanabe, G; Taya, K

    1998-03-01

    Male copulatory behavior and the function of the hypothalamo-hypophysial-gonadal axis in hypothyroid male rats were investigated in the present study. Hypothyroidism was induced by thyroidectomy or thiouracil. In male copulatory behavior test, intromission latencies in hypothyroid rats were significantly longer than those in euthyroid rats and ejaculation frequencies were reduced in hypothyroid male rats compared to control rats without reduction of plasma concentrations of testosterone. These changes in copulatory behavior in hypothyroid male rats were restored to control levels by administration of T4 (5 micrograms/rat). Hypothyroidism decreased adrenal weights, and basal and peak concentrations of corticosterone during diurnal variation, whereas it increased peak concentrations of ACTH in adult male rats. These results indicate that hypothyroidism causes adrenal dysfunction directly and results in hypersecretion of ACTH. The adrenal disturbance observed in hypothyroid rats may affect male copulatory behavior.

  15. Effects of estradiol and progesterone on vertebral collagen, glycosaminoglycans and phosphatases in ovariectomized adult rats.

    PubMed

    Gopala Krishnan, V; Arunakaran, J; Govindarajulu, P; Srinivasan, N

    2003-03-01

    Vertebral collagen, glycosaminoglycans (GAGs), tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) were measured in ovariectomized (ovx) adult Wistar rats treated with estradiol (E 2 ) (10 micro g/kg BW for 35 days on alternate days, and progesterone (P 4 ) (140 micro g/kg BW for 35 days on alternate days) in E 2 + P 4 treated rats. P 4 given alone or in combination with E 2 significantly increased the levels of collagen in the vertebral bone. Neither ovx nor E 2 treatment altered the concentration of collagen in these rats. Administration of E 2 or P 4 significantly decreased the concentration of hyaluronic acid (HA), but remaining unaffected when a combination of these steroids was given. In contrast to their effect on HA, E 2 and P 4 each significantly increased the levels of chondroitin sulfate (CS) in the vertebral bone. The specific activity of ALP was decreased after ovx. E 2 and P 4 alone or in combination also registered a significant decrease in the activities of ALP and TRAP. The results suggest that E 2 and P 4 each exert definite effects on vertebral bone turnover in ovariectomized rats.

  16. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity

    PubMed Central

    van de Heijning, Bert J. M.; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M.

    2015-01-01

    Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%–75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed. PMID:26184291

  17. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity.

    PubMed

    van de Heijning, Bert J M; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M

    2015-07-08

    Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%-75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed.

  18. Behavioural and biochemical effects in the adult rat after prolonged postnatal administration of clozapine.

    PubMed

    Cuomo, V; Cagiano, R; Mocchetti, I; Coen, E; Cattabeni, F; Racagni, G

    1983-01-01

    Rats were administered 10 mg/kg SC of clozapine (C) or vehicle solution (S) daily from day 1 after birth until 20 days of age. At 60 days of age (40 days after the postnatal treatment with C or S was interrupted) the stereotyped behaviour and the effects on locomotor activity elicited by apomorphine in S- and C-pretreated rats were investigated. The intensity of stereotyped behaviour as well as the decrement in locomotion induced by apomorphine (0.5--1 mg/kg SC) were not influenced by chronic C administration during development. Finally, at 80 days of age (60 days after the postnatal treatment with C or S was interrupted) rats were subjected to a differential reinforcement of low rates schedule (DRL15s). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf less than or equal to 2.5) was significantly more rapid in S-pretreated rats than in C-pretreated ones. In parallel biochemical experiments, homovanillic acid (HVA) content was measured in striatum in rats at 60 days of age (40 days after the postnatal treatment with C or S was interrupted). The results indicate that even if an acute challenge dose of 10 mg/kg C shows a certain degree of tolerance a single dose of 20 mg/kg C is still able to increase striatal HVA concentration in chronic C-pretreated animals. These data indicate that early postnatal administration of a non-cataleptogenic neuroleptic, like C, induces, in the adult rat, behavioural and biochemical changes which significantly differ from those elicited by a cataleptogenic neuroleptic, like haloperidol.

  19. Effect of chronic hyperoxic exposure on duroquinone reduction in adult rat lungs.

    PubMed

    Audi, Said H; Bongard, Robert D; Krenz, Gary S; Rickaby, David A; Haworth, Steven T; Eisenhauer, Jessica; Roerig, David L; Merker, Marilyn P

    2005-11-01

    NAD(P)H:quinone oxidoreductase 1 (NQO1) plays a dominant role in the reduction of the quinone compound 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ) to durohydroquinone (DQH2) on passage through the rat lung. Exposure of adult rats to 85% O2 for > or =7 days stimulates adaptation to the otherwise lethal effects of >95% O2. The objective of this study was to examine whether exposure of adult rats to hyperoxia affected lung NQO1 activity as measured by the rate of DQ reduction on passage through the lung. We measured DQH2 appearance in the venous effluent during DQ infusion at different concentrations into the pulmonary artery of isolated perfused lungs from rats exposed to room air or to 85% O2. We also evaluated the effect of hyperoxia on vascular transit time distribution and measured NQO1 activity and protein in lung homogenate. The results demonstrate that exposure to 85% O2 for 21 days increases lung capacity to reduce DQ to DQH2 and that NQO1 is the dominant DQ reductase in normoxic and hyperoxic lungs. Kinetic analysis revealed that 21-day hyperoxia exposure increased the maximum rate of pulmonary DQ reduction, Vmax, and the apparent Michaelis-Menten constant for DQ reduction, Kma. The increase in Vmax suggests a hyperoxia-induced increase in NQO1 activity of lung cells accessible to DQ from the vascular region, consistent qualitatively but not quantitatively with an increase in lung homogenate NQO1 activity in 21-day hyperoxic lungs. The increase in Kma could be accounted for by approximately 40% increase in vascular transit time heterogeneity in 21-day hyperoxic lungs.

  20. Combination therapy for the cardiovascular effects of perinatal lead exposure in young and adult rats.

    PubMed

    Gaspar, Andréia Fresneda; Cordellini, Sandra

    2014-09-01

    Combination therapy can play a significant role in the amelioration of several toxic effects of lead (Pb) and recovery from associated cardiovascular changes. To investigate the effects of combination therapy on the cardiovascular effects of perinatal lead exposure in young and adult rats Methods: Female Wistar rats received drinking water with or without 500 ppm of Pb during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were or were not exposed to Pb in the perinatal period received meso-dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of these compounds for 30 additional days. Noradrenaline response curves were plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats stratified by perinatal Pb exposure (exposed/unexposed) and treatment received (treated/untreated). Systolic blood pressure was evaluated and shown to be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in the corresponding control age groups: 117.8 ± 3.9*, 135.2 ± 1.3*, 139.6 ± 1.6*, and 131.7 ± 2.8*, respectively and 107.1 ± 1.8, 118.8 ± 2.1, 126.1 ± 1.1, and 120.5 ± 2.2, respectively (p < 0.05). Increased reactivity to noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and 100-day-old exposed rats, and the maximum responses (g of tension) in the respective Pb-exposed and control age groups were as follows: 3.43 ± 0.16*, 4.32 ± 0.18*, and 4.21 ± 0.23*, respectively and 2.38 ± 0.33, 3.37 ± 0.13, and 3.22 ± 0.21, respectively (p < 0.05). All treatments reversed the changes in vascular reactivity to noradrenaline in rats perinatally exposed to Pb. The combination therapy resulted in an earlier restoration of blood pressure in Pb-exposed rats compared with the monotherapies, except for enalapril therapy in young rats. These findings represent a new approach to the development of therapeutic protocols for the treatment of Pb-induced hypertension.

  1. Combination Therapy for the Cardiovascular Effects of Perinatal Lead Exposure in Young and Adult Rats

    PubMed Central

    Gaspar, Andréia Fresneda; Cordellini, Sandra

    2014-01-01

    Background: Combination therapy can play a significant role in the amelioration of several toxic effects of lead (Pb) and recovery from associated cardiovascular changes. Objective: To investigate the effects of combination therapy on the cardiovascular effects of perinatal lead exposure in young and adult rats Methods: Female Wistar rats received drinking water with or without 500 ppm of Pb during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were or were not exposed to Pb in the perinatal period received meso-dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of these compounds for 30 additional days. Noradrenaline response curves were plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats stratified by perinatal Pb exposure (exposed/unexposed) and treatment received (treated/untreated). Results: Systolic blood pressure was evaluated and shown to be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in the corresponding control age groups: 117.8 ± 3.9*, 135.2 ± 1.3*, 139.6 ± 1.6*, and 131.7 ± 2.8*, respectively and 107.1 ± 1.8, 118.8 ± 2.1, 126.1 ± 1.1, and 120.5 ± 2.2, respectively (p < 0.05). Increased reactivity to noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and 100-day-old exposed rats, and the maximum responses (g of tension) in the respective Pb-exposed and control age groups were as follows: 3.43 ± 0.16*, 4.32 ± 0.18*, and 4.21 ± 0.23*, respectively and 2.38 ± 0.33, 3.37 ± 0.13, and 3.22 ± 0.21, respectively (p < 0.05). Conclusions: All treatments reversed the changes in vascular reactivity to noradrenaline in rats perinatally exposed to Pb. The combination therapy resulted in an earlier restoration of blood pressure in Pb-exposed rats compared with the monotherapies, except for enalapril therapy in young rats. These findings represent a new approach to the development of therapeutic protocols for the treatment of Pb

  2. Protective effects of Peganum harmala extracts on thiourea-induced diseases in adult male rat.

    PubMed

    Hamden, Khaled; Masmoudi, Hatem; Ellouz, Feriel; ElFeki, Adelfatteh; Carreau, Serge

    2008-01-01

    Cancers and hepatoprotective prevention using traditional medicines have attracted increasing interest. The aim of our study was to characterize the putative protective effects of ethanol and chloroform extracts of Peganum harmala on thiourea-induced diseases in adult male rat. We seek to determine the effects of these plant extracts on body weight, thyroid and endocrine cancer parameters. In addition the putative hepatoprotective effect was checked by the determination of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and the bilirubin level in the blood. Our data show that ethanol and chloroform extracts of Peganum harmala protected the animal against the carcinogenic effects induced by thiourea since neuron-specific enolase (NSE) and thyroglobulin (TG) levels were back to the normal range. In addition, the observed-hepatocytotoxicity after thiourea treatment was greatly reduced (AST and ALT activities were respectively 270 IU/l and 60 IU/l and in the same order of magnitude as in the untreated rats) as well as the bilirubin levels (6 micromol/l) especially for animals receiving the choroform preparation. Therefore we may suggest that extracts of Peganum harmala are efficient to reduce the toxicity induced by thiourea in male rat as far as the above parameters are concerned.

  3. Effects of morphine on thermal sensitivity in adult and aged rats.

    PubMed

    Morgan, Drake; Mitzelfelt, Jeremiah D; Koerper, Lorraine M; Carter, Christy S

    2012-06-01

    There are contradictory data regarding older individuals' sensitivity to pain stimulation and opioid administration. Adult (12-16 months; n = 10) and aged (27-31 months; n = 7) male F344xBN rats were tested in a thermal sensitivity procedure where the animal chooses to remain in one of two compartments with floors maintained at various temperatures ranging from hot (45°C) through neutral (30°C) to cold (15°C). Effects of morphine were determined for three temperature comparisons (ie, hot/neutral, cold/neutral, and hot/cold). Aged rats were more sensitive to cold stimulation during baseline. Morphine produced antinociception during hot thermal stimulation, but had no effect on cold stimulation. The antinociceptive (and locomotor-altering) effects of morphine were attenuated in aged rats. These data demonstrate age-related differences in baseline thermal sensitivity and responsiveness to opioids. Based on behavioral and physiological requirements of this procedure, it is suggested that thermal sensitivity may provide a relevant animal model for the assessment of pain and antinociception.

  4. Effects of Maternal Behavior Induction and Pup Exposure on Neurogenesis in Adult, Virgin Female Rats

    PubMed Central

    Furuta, Miyako; Bridges, Robert S.

    2009-01-01

    The states of pregnancy and lactation bring about a range of physiological and behavioral changes in the adult mammal that prepare the mother to care for her young. Cell proliferation increases in the subventricular zone (SVZ) of the female rodent brain during both pregnancy and lactation when compared to that in cycling, diestrous females. In the present study, the effects of maternal behavior induction and pup exposure on neurogenesis in nulliparous rats were examined in order to determine whether maternal behavior itself, independent of pregnancy and lactation, might affect neurogenesis. Adult, nulliparous, Sprague-Dawley, female rats were exposed daily to foster young in order to induce maternal behavior. Following the induction of maternal behavior each maternal subject plus females that were exposed to pups for a comparable number of test days, but did not display maternal behavior, and subjects that had received no pup exposure were injected with bromodeoxyuridine (BrdU, 90 mg/kg, i.v.). Brain sections were double-labeled for BrdU and the neural marker, NeuN, to examine the proliferating cell population. Increases in the number of double-labeled cells were found in the maternal virgin brain when compared with the number of double-labeled cells present in non-maternal, pup-exposed nulliparous rats and in females not exposed to young. No changes were evident in the dentate gyrus of the hippocampus as a function of maternal behavior. These data indicate that in nulliparous female rats maternal behavior itself is associated with the stimulation of neurogenesis in the SVZ. PMID:19712726

  5. Effect of agomelatine on adult hippocampus apoptosis and neurogenesis using the stress model of rats.

    PubMed

    Yucel, Atakan; Yucel, Nermin; Ozkanlar, Seckin; Polat, Elif; Kara, Adem; Ozcan, Halil; Gulec, Mustafa

    2016-04-01

    Agomelatine (AG) is an agonist of melatonin receptors and an antagonist of the 5-HT2C-receptor subtype. The chronobiotic properties of AG are of significant interest due to the disorganization of internal rhythms, which might play a role in the pathophysiology of depression. The present study was designed to assess the effects of the antidepressant-like activity of AG, a new antidepressant drug, on adult neurogenesis and apoptosis using stress-exposed rat brains. Over the period of 1 week, the rats were exposed to light stress twice a day for 1h. After a period of 1 week, the rats were given AG treatment at a dose of either 10mg/kg or 40mg/kg for 15 days. The animals were then scarified, and the obtained tissue sections were stained with immuno-histochemical anti-BrdU, Caspase-3, and Bcl-2 antibodies. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured biochemically using a BDNF Elisa kit. Biochemical BDNF analysis revealed a high concentration of BDNF in the serum of the stress-exposed group, but the concentrations of BDNF were much lower those of the AG-treated groups. Immuno-histochemical analysis revealed that AG treatment decreased the BrdU-positive and Bcl-2-positive cell densities and increased the Caspase-3-positive cell density in the hippocampus of stress-induced rats as compared to those of the stress group. The results of the study demonstrated that AG treatment ameliorated the hippocampal apoptotic cells and increased hippocampal neurogenesis. These results also strengthen the possible relationship between depression and adult neurogenesis, which must be studied further.

  6. Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat.

    PubMed

    Wang, Hui-Dong; Dunnavant, Floyd D; Jarman, Tabitha; Deutch, Ariel Y

    2004-07-01

    The generation of new cells in the adult mammalian brain may significantly modify pathophysiological processes in neuropsychiatric disorders. We examined the ability of chronic treatment with the antipsychotic drugs (APDs) olanzapine and haloperidol to increase the number and survival of newly generated cells in the prefrontal cortex (PFC) and striatal complex of adult male rats. Animals were treated with olanzapine or haloperidol for 3 weeks and then injected with 5-bromo-2'-deoxyuridine (BrdU) to label mitotic cells. Half of the animals continued on the same APD for two more weeks after BrdU challenge, with the other half receiving vehicle during this period. Olanzapine but not haloperidol significantly increased both the total number and density of BrdU-labeled cells in the PFC and dorsal striatum; no effect was observed in the nucleus accumbens. Continued olanzapine treatment after the BrdU challenge did not increase the survival of newly generated cells. The newly generated cells in the PFC did not express the neuronal marker NeuN. Despite the significant increase in newly generated cells in the PFC of olanzapine-treated rats, the total number of these cells is low, suggesting that the therapeutic effects of atypical APD treatment may not be due to the presence of newly generated cells that have migrated to the cortex.

  7. Effects of different exercise protocols on ethanol-induced spatial memory impairment in adult male rats.

    PubMed

    Hashemi Nosrat Abadi, T; Vaghef, L; Babri, S; Mahmood-Alilo, M; Beirami, M

    2013-06-01

    Chronic ethanol consumption is often accompanied by numerous cognitive deficits and may lead to long-lasting impairments in spatial learning and memory. The aim of the present study was to evaluate the therapeutic potential of regular treadmill exercise on hippocampal-dependent memory in ethanol-treated rats. Spatial memory was tested in a Morris Water Maze task. Adult male Wistar rats were exposed to ethanol (4 g/kg, 20% v/v for 4 weeks) and effects of three exercise protocols (pre-ethanol, post-ethanol and pre-to-post-ethanol treatment) were examined. Results showed that ethanol exposure resulted in longer escape latencies during the acquisition phase of the Morris Water Maze task. Moreover, all three exercise protocols significantly decreased the latency to locate the hidden platform. During the probe trial, ethanol led to decreased time spent in the target quadrant. In contrast, performance on the probe trial was significantly better in the rats that had done the post- and pre-to-post-ethanol, but not pre-ethanol, exercises. These findings suggest that treadmill running can attenuate the adverse effects of chronic ethanol exposure on spatial memory, and may serve as a non-pharmacological alcohol abuse treatment.

  8. Differential Behavioral and Neurobiological Effects of Chronic Corticosterone Treatment in Adolescent and Adult Rats

    PubMed Central

    Li, Jitao; Xie, Xiaomeng; Li, Youhong; Liu, Xiao; Liao, Xuemei; Su, Yun-Ai; Si, Tianmei

    2017-01-01

    Adolescence is a critical period with ongoing maturational processes in stress-sensitive systems. While adolescent individuals show heightened stress-induced hormonal responses compared to adults, it is unclear whether and how the behavioral and neurobiological consequences of chronic stress would differ between the two age groups. Here we address this issue by examining the effects of chronic exposure to the stress hormone, corticosterone (CORT), in both adolescent and adult animals. Male Sprague-Dawley (SD) rats were injected intraperitoneally with CORT (40 mg/kg) or vehicle for 21 days during adolescence (post-natal day (PND) 29–49) or adulthood (PND 71–91) and then subjected to behavioral testing or sacrifice for western blot analyses. Despite of similar physical and neuroendocrine effects in both age groups, chronic CORT treatment produced a series of behavioral and neurobiological effects with striking age differences. While CORT-treated adult animals exhibited decreased sucrose preference, increased anxiety levels and cognitive impairment, CORT-treated adolescent animals demonstrated increased sucrose preference, decreased anxiety levels, and increased sensorimotor gating functions. These differential behavioral alterations were accompanied by opposite changes in the two age groups in the expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylation of the obligatory subunit of the NMDA receptor, GluN1, and PSD-95 in rat hippocampus. These results suggest that prolonged glucocorticoid exposure during adolescence produces different behavioral and neurobiological effects from those in adulthood, which may be due to the complex interaction between glucocorticoids and the ongoing neurodevelopmental processes during this period. PMID:28210212

  9. Effects of 5-fluorouracil on the thiamin status of adult female rats.

    PubMed

    Basu, T K; Aksoy, M; Dickerson, J W

    1979-01-01

    The effect of 5-fluorouracil on the thiamin status of normal female adult rats has been investigated. Pre-treatment of the animals with the cytotoxic drug daily for 3 successive days resulted in a significant decrease in hepatic concentrations of thiamin concomitant with a decrease in thiamin-dependent transketolase enzyme activity and an increase in thiamin-pyrophosphate-(TPP-)stimulating effect in whole blood when compared with those of pair-fed control animals. The TPP effect of transketolase enzyme activity was also increased by 5-fluorouracil in vitro. Furthermore, the treatment with 5-fluorouracil resulted in decreased liver and spleen concentrations without affecting the urinary excretory levels of thiamin in animals supplemented with large doses of the vitamin. Giving a dose comparable to a human therapeutic dose caused a similar increase in the TPP effect. These results indicate that treatment with 5-fluorouracil may be associated with thiamin deficiency by increasing either the utilization or the breakdown of thiamin.

  10. Developmental effects of wheel running on hippocampal glutamate receptor expression in young and mature adult rats

    PubMed Central

    Staples, Miranda C.; Somkuwar, Sucharita S.; Mandyam, Chitra D.

    2015-01-01

    Recent evidence suggests that the behavioral benefits associated with voluntary wheel running in rodents may be due to modulation of glutamatergic transmission in the hippocampus, a brain region implicated in learning and memory. However, the expression of the n-Methyl-d-Aspartate glutamate receptor subunits (GluNs) in the hippocampus in response to chronic sustained voluntary wheel running has not yet been investigated. Further, the developmental effects during young and mature adulthood on wheel running output and GluN expression in hippocampal subregions has not been determined, and therefore is the main focus of this investigation. Eight-week-old and sixteen-week-old male Wistar rats were housed in home cages with free access to running wheels and running output was monitored for four weeks. Wheel access was terminated and tissue from the dorsal and ventral hippocampi were processed for Western blot analysis of GluN subunit expression. Young adult runners demonstrated an escalation in running output but this behavior was not evident in mature adult runners. In parallel, young adult runners demonstrated a significant increase in total GluN (1 and 2A) subunit expression in the dorsal hippocampus, and an opposing effect in the ventral hippocampus compared to age-matched sedentary controls; these changes in total protein expression were not associated with significant alterations in the phosphorylation of the GluN subunits. In contrast, mature adult runners demonstrated a reduction in total GluN2A expression in the dorsal hippocampus, without producing alterations in the ventral hippocampus compared to age-matched sedentary controls. In conclusion, differential running activity-mediated modulation of GluN subunit expression in the hippocampal subregions was revealed to be associated with developmental effects on running activity, which may contribute to altered hippocampal synaptic activity and behavioral outcomes in young and mature adult subjects. PMID:26220171

  11. Developmental effects of wheel running on hippocampal glutamate receptor expression in young and mature adult rats.

    PubMed

    Staples, M C; Somkuwar, S S; Mandyam, C D

    2015-10-01

    Recent evidence suggests that the behavioral benefits associated with voluntary wheel running in rodents may be due to modulation of glutamatergic transmission in the hippocampus, a brain region implicated in learning and memory. However, the expression of the glutamatergic ionotropic N-methyl-d-aspartate receptor (GluN) in the hippocampus in response to chronic sustained voluntary wheel running has not yet been investigated. Further, the developmental effects during young and mature adulthood on wheel running output and GluN expression in hippocampal subregions has not been determined, and therefore is the main focus of this investigation. Eight-week-old and 16-week-old male Wistar rats were housed in home cages with free access to running wheels and running output was monitored for 4weeks. Wheel access was terminated and tissues from the dorsal and ventral hippocampi were processed for Western blot analysis of GluN subunit expression. Young adult runners demonstrated an escalation in running output but this behavior was not evident in mature adult runners. In parallel, young adult runners demonstrated a significant increase in total GluN (1 and 2A) subunit expression in the dorsal hippocampus (DH), and an opposing effect in the ventral hippocampus (VH) compared to age-matched sedentary controls; these changes in total protein expression were not associated with significant alterations in the phosphorylation of the GluN subunits. In contrast, mature adult runners demonstrated a reduction in total GluN2A expression in the DH, without producing alterations in the VH compared to age-matched sedentary controls. In conclusion, differential running activity-mediated modulation of GluN subunit expression in the hippocampal subregions was revealed to be associated with developmental effects on running activity, which may contribute to altered hippocampal synaptic activity and behavioral outcomes in young and mature adult subjects.

  12. Gender differences in the effect of adult amphetamine on cognitive functions of rats prenatally exposed to methamphetamine.

    PubMed

    Macúchová, E; Nohejlová, K; Slamberová, R

    2014-08-15

    Psychostimulants have been shown to affect brain regions involved in the process of learning and memory consolidation. It has been shown that females are more sensitive to the effects of drugs than males. The aim of our study was to investigate how prenatal methamphetamine (MA) exposure and application of amphetamine (AMP) in adulthood would affect spatial learning of adult female and male rats. Mothers of the tested offspring were exposed to injections of MA (5mg/kg) or saline (SA) throughout the entire gestation period. Cognitive functions of adult rats were evaluated in the Morris Water Maze (MWM) tests. Adult offspring were injected daily with AMP (5mg/kg) or SA through the period of MWM testing. Our data from the MWM tests demonstrates the following. Prenatal MA exposure did not change the learning ability of adult male and female rats. However, AMP administration to adult animals affected cognitive function in terms of exacerbation of spatial learning (increasing the latency to reach the hidden platform, the distance traveled and the search error) only in female subjects. There were sex differences in the speed of swimming. Prenatal MA exposure and adult AMP treatment increased the speed of swimming in female groups greater than in males. Overall, the male subjects showed a better learning ability than females. Thus, our results indicate that the adult AMP treatment affects the cognitive function and behavior of rats in a sex-specific manner, regardless of prenatal exposure. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Ablating adult neurogenesis in the rat has no effect on spatial processing: evidence from a novel pharmacogenetic model.

    PubMed

    Groves, James O; Leslie, Isla; Huang, Guo-Jen; McHugh, Stephen B; Taylor, Amy; Mott, Richard; Munafò, Marcus; Bannerman, David M; Flint, Jonathan

    2013-01-01

    The function of adult neurogenesis in the rodent brain remains unclear. Ablation of adult born neurons has yielded conflicting results about emotional and cognitive impairments. One hypothesis is that adult neurogenesis in the hippocampus enables spatial pattern separation, allowing animals to distinguish between similar stimuli. We investigated whether spatial pattern separation and other putative hippocampal functions of adult neurogenesis were altered in a novel genetic model of neurogenesis ablation in the rat. In rats engineered to express thymidine kinase (TK) from a promoter of the rat glial fibrillary acidic protein (GFAP), ganciclovir treatment reduced new neurons by 98%. GFAP-TK rats showed no significant difference from controls in spatial pattern separation on the radial maze, spatial learning in the water maze, contextual or cued fear conditioning. Meta-analysis of all published studies found no significant effects for ablation of adult neurogenesis on spatial memory, cue conditioning or ethological measures of anxiety. An effect on contextual freezing was significant at a threshold of 5% (P = 0.04), but not at a threshold corrected for multiple testing. The meta-analysis revealed remarkably high levels of heterogeneity among studies of hippocampal function. The source of this heterogeneity remains unclear and poses a challenge for studies of the function of adult neurogenesis.

  14. Effects of Neonatal Dexamethasone Exposure on Adult Neuropsychiatric Traits in Rats

    PubMed Central

    Robertson, Donald; Rodger, Jennifer; Martin-Iverson, Mathew T.

    2016-01-01

    The effects of early life stress in utero or in neonates has long-term consequences on hypothalamic-pituitary-adrenal (HPA) stress axis function and neurodevelopment. These effects extend into adulthood and may underpin a variety of mental illnesses and be related to various developmental and cognitive changes. We examined the potential role of neonatal HPA axis activation on adult psychopathology and dopamine sensitivity in the mature rat using neonatal exposure to the synthetic glucocorticoid receptor agonist and stress hormone, dexamethasone. We utilized a comprehensive battery of assessments for behaviour, brain function and gene expression to determine if elevated early life HPA activation is associated with adult-onset neuropsychiatric traits. Dexamethasone exposure increased startle reactivity under all conditions tested, but decreased sensitivity of sensorimotor gating to dopaminergic disruption–contrasting with what is observed in several neuropsychiatric diseases. Under certain conditions there also appeared to be mild long-term changes in stress and anxiety-related behaviours with neonatal dexamethasone exposure. Electrophysiology revealed that there were no consistent neuropsychiatric abnormalities in auditory processing or resting state brain function with dexamethasone exposure. However, neonatal dexamethasone altered auditory cortex glucocorticoid activation, and auditory cortex synchronization. Our results indicate that neonatal HPA axis activation by dexamethasone alters several aspects of adult brain function and behaviour and may induce long-term changes in emotional stress-reactivity. However, neonatal dexamethasone exposure is not specifically related to any particular neuropsychiatric disease. PMID:27936175

  15. Anxiogenic-like effects of fluoxetine render adult male rats vulnerable to the effects of a novel stress.

    PubMed

    Gomez, Francisca; García-García, Luis

    2017-02-01

    Fluoxetine (FLX) has paradoxical anxiogenic-like effects during the acute phase of treatment. In adolescent (35d-old) male rats, the stress-like effects induced by short-term (3d-4d) FLX treatment appear to involve up-regulation of paraventricular nucleus (PVN) arginine vasopressin (AVP) mRNA. However, studies on FLX-induced anxiety-like effects in adult rodents are inconclusive. Herein, we sought to study the response of adult male rats (60-65d-old) to a similar FLX treatment, also investigating how the stressful component, inherent to our experimental conditions, contributed to the responses. We show that FLX acutely increased plasma corticosterone concentrations while it attenuated the stress-induced-hyperthermia (SIH) as well as it reduced (≈40%) basal POMC mRNA expression in the arcuate nucleus (ARC). However, FLX did not alter the basal expression of PVN-corticotrophin-releasing hormone (CRH), anterior pituitary-pro-opiomelanocortin (POMC) and raphe nucleusserotonin transporter (SERT). Nonetheless, some regressions point towards the plausibility that FLX activated the hypothalamic-pituitary-adrenal (HPA). The behavioral study revealed that FLX acutely increased emotional reactivity in the holeboard, effect followed by a body weight loss of ≈2.5% after 24h. Interestingly, i.p. injection with vehicle did not have behavioral effects, furthermore, after experiencing the stressful component of the holeboard, the rats kept eating and gaining weight as normal. By contrast, the stress-naïve rats reduced food intake and gained less weight although maintaining a positive energy state. Therefore, on one hand, repetition of a mild stressor would unchain compensatory mechanisms to restore energy homeostasis after stress increasing the resiliency to novel stressors. On the other hand, FLX might render stressed adult rats vulnerable to novel stressors through the emergence of counter-regulatory changes, involving HPA axis activation and diminished sympathetic output

  16. The effects of perinatal tebuconazole exposure on adult neurological, immunological, and reproductive function in rats.

    PubMed

    Moser, V C; Barone, S; Smialowicz, R J; Harris, M W; Davis, B J; Overstreet, D; Mauney, M; Chapin, R E

    2001-08-01

    Studies are under way to address concerns of potential persistent immunotoxic, reproductive, and neurotoxic effects of perinatal exposure to several pesticides. Tebuconazole, a triazole fungicide, was evaluated as part of this project. Sprague-Dawley dams were administered tebuconazole (0, 6, 20, or 60 mg/kg) by oral gavage daily from gestational day 14 to postnatal day (PND)7; the pups were then dosed daily at the same levels from PND7-42. Separate groups of rats were used for testing of immunological parameters, neurobehavioral testing using a screening battery of functional tests, and cognitive evaluations. Other groups of rats were evaluated for reproductive development and function, while yet others were sacrificed at the end of the dosing period for histological analyses of major organs systems, including neuropathological assessments. Pup viability and body weight were decreased in the highest dose group. There were no differences in the fertility indices in the exposed rats mated as adults. In the sheep RBC-immunized high-dose rats, spleen weights and cellularity were increased, and the ratio of cell types was altered compared to controls. There were, however, no biologically significant changes in the immune function of these rats. At necropsy on PND46 or 152, kidney, liver, and spleen weights were altered by tebuconazole treatment, but a dose-response relationship was not clear for most organs; only decreased kidney and increased liver weights were consistent in both sexes. Histological analyses were generally unremarkable outside of the brain. One month after the end of dosing, acquisition of learning the platform location in a water tank (i.e., Morris water maze) was impaired in the high-dose group; there were no differences in neuromuscular ability, motor activity, or swim speed to account for this finding. Furthermore, there was no effect on recall of the position during a free-swim trial. Neuropathological evaluations revealed pyknotic cells across

  17. Effect of Norbinaltorphimine on Δ9-Tetrahydrocannabinol (THC)-Induced Taste Avoidance in Adolescent and Adult Sprague-Dawley Rats

    PubMed Central

    Flax, Shaun M.; Wakeford, Alison G.P.; Cheng, Kejun; Rice, Kenner C.; Riley, Anthony L.

    2017-01-01

    Rationale The aversive effects of Δ9-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the aversive effects induced by KOR agonists, a different mechanism might mediate the aversive effects of THC in this age group. Objectives The present study was designed to assess the impact of KOR antagonism on the aversive effects of THC in adolescent and adult rats using the conditioned taste avoidance (CTA) procedure. Methods Following a single pretreatment injection of norbinaltorphimine (norBNI; 15 mg/kg), CTAs induced by THC (0, 0.56, 1.0, 1.8 and 3.2 mg/kg) were assessed in adolescent (n = 84) and adult (n = 83) Sprague Dawley rats. Results The KOR antagonist, norBNI, had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. Conclusions That norBNI had no significant effect on THC-induced avoidance in adults and a minor and inconsistent effect in adolescents demonstrates that the aversive effects of THC are not mediated by KOR activity as assessed by the CTA design in Sprague Dawley rats. PMID:26025420

  18. The effects of biological sex and gonadal hormones on learning strategy in adult rats.

    PubMed

    Hawley, Wayne R; Grissom, Elin M; Barratt, Harriet E; Conrad, Taylor S; Dohanich, Gary P

    2012-02-28

    When learning to navigate toward a goal in a spatial environment, rodents employ distinct learning strategies that are governed by specific regions of the brain. In the early stages of learning, adult male rats prefer a hippocampus-dependent place strategy over a striatum-dependent response strategy. Alternatively, female rats exhibit a preference for a place strategy only when circulating levels of estradiol are elevated. Notably, male rodents typically perform better than females on a variety of spatial learning tasks, which are mediated by the hippocampus. However, limited research has been done to determine if the previously reported male spatial advantage corresponds with a greater reliance on a place strategy, and, if the male preference for a place strategy is impacted by removal of testicular hormones. A dual-solution water T-maze task, which can be solved by adopting either a place or a response strategy, was employed to determine the effects of biological sex and hormonal status on learning strategy. In the first experiment, male rats made more correct arm choices than female rats during training and exhibited a bias for a place strategy on a probe trial. The results of the second experiment indicated that testicular hormones modulated arm choice accuracy during training, but not the preference for a place strategy. Together, these findings suggest that the previously reported male spatial advantage is associated with a greater reliance on a place strategy, and that only performance during the training phase of a dual-solution learning task is impacted by removal of testicular hormones.

  19. Effects of increased occlusal vertical dimension on the jaw-opening reflex in adult rats.

    PubMed

    Makiguchi, Mio; Funaki, Yukiha; Kato, Chiho; Okihara, Hidemasa; Ishida, Takayoshi; Yabushita, Tadachika; Kokai, Satoshi; Ono, Takashi

    2016-12-01

    Malocclusion with deep overbite and facial esthetics improve when facial height is intentionally increased during orthodontic extrusion of the posterior teeth. Thus, a better understanding of post-treatment stability of increased occlusal vertical dimension (iOVD) in adult patients is important. We focused on the jaw-opening reflex (JOR), which plays an important role in the control of jaw movements during mastication, and investigated the effects of iOVD on the JOR in rats with an electrophysiological technique. One hundred and twenty 13-week-old male Wistar rats were randomly divided into control and experimental groups. Rats in the experimental group received a 2-mm buildup of composite resin on the maxillary molars at 13 weeks of age. The JOR was induced by low-intensity electrical stimulation of the left inferior alveolar nerve. The electromyographic responses were recorded from the digastric muscle at 13, 14, 15, 17, 19, and 23 weeks of age. JOR properties including latency, duration, and peak-to-peak amplitude were measured and compared between the groups. The latency of the JOR was significantly longer and the peak-to-peak amplitude was significantly smaller in the experimental group than in the control group from 14 to 19 weeks of age, while the reflex duration was not significantly different. Intra-group comparisons of the latency and peak-to-peak amplitudes among rats 14-19 weeks of age were significantly different between the experimental group and the control group. iOVD affected the latency and amplitude of the JOR but not the duration. The JOR adapted after 10 weeks of iOVD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Exogenous Testosterone, Finasteride and Castration Effects on Testosterone, Insulin, Zinc and Chromium in Adult Male Rats

    PubMed Central

    Yousofvand, Namdar; Zarei, Fatemeh; Ghanbari, Ali

    2013-01-01

    Background: Although effects of trace elements on secretion of sex steroids and insulin have been studied, the effects of these hormones on serum level of trace elements have been rarely investigated. The aim of the present study was to evaluate the effect of testosterone and finasteride administration and castration on serum levels of testosterone, insulin, zinc and chromium. Methods: Male adult rats (n = 32) were divided into 4 groups (n = 8). Group 1, control; Group 2, castration, castration was done at the first day of the study; Group 3, finasteride (20 mg/kg/day, dissolved in drinking water) and Group 4, testosterone (5 mg/kg/day, i.p.). At the end of the period of the study (35 days), serum testosterone, insulin, zinc and chromium levels were determined in the blood samples collected directly from the right atrium of the heart of the animals. Results: The data indicated that the serum levels of testosterone, insulin and zinc were significantly increased (P<0.01) in testosterone-administrated and finasteride groups, but the level of chromium was decreased in both groups (P<0.01). Castrated group had the lowest serum levels of testosterone, insulin and zinc (P<0.05). Also, the levels of serum chromium in this group were increased. Conclusion: The study demonstrates that testosterone and finasteride increases insulin and zinc levels and decreases chromium levels in the serum of male adult rats. According to these data, it seems that testosterone may affect glucose cycle through effect on serum insulin levels and trace elements such as zinc and chromium. PMID:23279835

  1. Exogenous testosterone, finasteride and castration effects on testosterone, insulin, zinc and chromium in adult male rats.

    PubMed

    Yousofvand, Namdar; Zarei, Fatemeh; Ghanbari, Ali

    2013-01-01

    Although effects of trace elements on secretion of sex steroids and insulin have been studied, the effects of these hormones on serum level of trace elements have been rarely investigated. The aim of the present study was to evaluate the effect of testosterone and finasteride administration and castration on serum levels of testosterone, insulin, zinc and chromium. Male adult rats (n = 32) were divided into 4 groups (n = 8). Group 1, control; Group 2, castration, castration was done at the first day of the study; Group 3, finasteride (20 mg/kg/day, dissolved in drinking water) and Group 4, testosterone (5 mg/kg/day, i.p.). At the end of the period of the study (35 days), serum testosterone, insulin, zinc and chromium levels were determined in the blood samples collected directly from the right atrium of the heart of the animals. The data indicated that the serum levels of testosterone, insulin and zinc were significantly increased (P<0.01) in testosterone-administrated and finasteride groups, but the level of chromium was decreased in both groups (P<0.01). Castrated group had the lowest serum levels of testosterone, insulin and zinc (P<0.05). Also, the levels of serum chromium in this group were increased. The study demonstrates that testosterone and finasteride increases insulin and zinc levels and decreases chromium levels in the serum of male adult rats. According to these data, it seems that testosterone may affect glucose cycle through effect on serum insulin levels and trace elements such as zinc and chromium.

  2. Maternal food restriction modulates cerebrovascular structure and contractility in adult rat offspring: effects of metyrapone

    PubMed Central

    Durrant, Lara M.; Khorram, Omid; Buchholz, John N.

    2014-01-01

    Although the effects of prenatal undernutrition on adult cardiovascular health have been well studied, its effects on the cerebrovascular structure and function remain unknown. We used a pair-fed rat model of 50% caloric restriction from day 11 of gestation to term, with ad libitum feeding after birth. We validated that maternal food restriction (MFR) stress is mediated by glucocorticoids by administering metyrapone, a corticosterone synthesis inhibitor, to MFR mothers at day 11 of gestation. At age 8 mo, offspring from Control, MFR, and MFR + Metyrapone groups were killed, and middle cerebral artery (MCA) segments were studied using vessel-bath myography and confocal microscopy. Colocalization of smooth muscle α-actin (SMαA) with nonmuscle (NM), SM1 and SM2 myosin heavy-chain (MHC) isoforms was used to assess smooth muscle phenotype. Our results indicate that artery stiffness and wall thickness were increased, pressure-evoked myogenic reactivity was depressed, and myofilament Ca2+ sensitivity was decreased in offspring of MFR compared with Control rats. MCA from MFR offspring exhibited a significantly greater SMαA/NM colocalization, suggesting that the smooth muscle cells had been altered toward a noncontractile phenotype. MET significantly reversed the effects of MFR on stiffness but not myogenic reactivity, lowered SMαA/NM colocalization, and increased SMαA/SM2 colocalization. Together, our data suggest that MFR alters cerebrovascular contractility via both glucocorticoid-dependent and glucocorticoid-independent mechanisms. PMID:24477541

  3. Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

    PubMed

    Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

    2017-02-01

    There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

  4. Effects of in utero exposure to Tityus bahiensis scorpion venom in adult rats.

    PubMed

    Dorce, Ana Leticia Coronado; Dorce, Valquiria Abrão Coronado; Nencioni, Ana Leonor Abrahão

    2010-01-01

    The toxicity of Tityus bahiensis scorpion venom is well known, but there are little data about the damage in offspring of dams that were exposed to the venom during pregnancy. The objective of this work was to determine the toxic effects of venom in adult offspring of Wistar rats exposed to venom in utero. Dams were divided into a control group, subcutaneously injected with saline solution on the 10th (GD10) and 16th (GD16) days, and two experimental groups, subcutaneously injected with venom (2.5mg/kg) on GD10 or GD16, respectively. Adult offspring were evaluated according to behavioral development and neuronal integrity in the hippocampus. Tests performed in the activity box and in the enriched environment demonstrated that males from GD10 had motor decrease. Females from GD10 showed a depressive-like state and were more anxious, as demonstrated by the forced swimming test and social interaction. The plus-maze discriminative avoidance task demonstrated that GD16 males had lower levels of anxiety. The number of neuronal cells was decreased in CA1, CA3 and CA4 hippocampal areas of males and females from GD10 group and in CA1 of females and CA4 of males from GD16 group. Thus, we conclude that venom exposure in pregnant dams causes subtle alteration in the behavioral and neuronal development of offspring in adult life in a gender-dependent manner. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  5. Differential mechanisms of ang (1-7)-mediated vasodepressor effect in adult and aged candesartan-treated rats.

    PubMed

    Bosnyak, S; Widdop, R E; Denton, K M; Jones, E S

    2012-01-01

    Angiotensin (1-7) (Ang (1-7)) causes vasodilator effects in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) via angiotensin type 2 receptors (AT(2)R). However, the role of vascular AT(2)R in aging is not known. Therefore, we examined the effect of aging on Ang (1-7)-mediated vasodepressor effects and vascular angiotensin receptor localization in aging. Blood pressure was measured in conscious adult (~17 weeks) and aged (~19 months) normotensive rats that received drug combinations in a randomised fashion over a 4-day protocol: (i) Ang (1-7) alone, (ii) AT(1)R antagonist, candesartan, alone, (iii) Ang (1-7) and candesartan, or (iv) Ang-(1-7), candesartan, and the AT(2)R antagonist, PD123319. In a separate group of animals, the specific MasR antagonist, A779, was administered in place of PD123319. Receptor localisation was also assessed in aortic sections from adult and aged WKY rats by immunofluorescence. Ang (1-7) reduced blood pressure (~15 mmHg) in adult normotensive rats although this effect was dependant on the background dose of candesartan. This depressor effect was reversed by AT(2)R blockade. In aged rats, the depressor effect of Ang (1-7) was evident but was now inhibited by either AT(2)R blockade or MasR blockade. At the same time, AT(2)R, MasR, and ACE2 immunoreactivity was markedly elevated in aortic sections from aged animals. These results indicate that the Ang (1-7)-mediated depressor effect was preserved in aged animals. Whereas Ang (1-7) effects were mediated exclusively via stimulation of AT(2)R in adult WKY, with aging the vasodepressor effect of Ang (1-7) involved both AT(2)R and MasR.

  6. Effects of Extremely Low Frequency Electromagnetic Fields on Vascular Permeability of Circumventricular Organs in the Adult Rat

    NASA Astrophysics Data System (ADS)

    Gutiérrez-Mercado, Y. K.; Cañedo-Dorantes, L.; Bañuelos-Pineda, J.; Serrano-Luna, G.; Feria-Velasco, A.

    2008-08-01

    The present work deals with the effects of extremely low frequency electromagnetic fields (ELF-EMF) on blood vessels permeability to non liposoluble substances of the circumventricular organs (CVO) of adult rats. Male Wistar adult rats were exposed to ELF-EMF and vascular permeability to colloidal carbon was investigated with the use of histological techniques. Results were compared to corresponding data from sham-exposed and control groups of animals. Exposure to ELF-EMF increased the CVO vascular permeability to colloidal carbon intravascularly injected, particularly in the subfornical organ, the median eminence, the pineal gland and the area postrema.

  7. Additive effects of maternal iron deficiency and prenatal immune activation on adult behaviors in rat offspring.

    PubMed

    Harvey, Louise; Boksa, Patricia

    2014-08-01

    Both iron deficiency (ID) and infection are common during pregnancy and studies have described altered brain development in offspring as a result of these individual maternal exposures. Given their high global incidence, these two insults may occur simultaneously during pregnancy. We recently described a rat model which pairs dietary ID during pregnancy and prenatal immune activation. Pregnant rats were placed on iron sufficient (IS) or ID diets from embryonic day 2 (E2) until postnatal day 7, and administered the bacterial endotoxin, lipopolysaccharide (LPS) or saline on E15/16. In this model, LPS administration on E15 caused greater induction of the pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor-α, in ID dams compared to IS dams. This suggested that the combination of prenatal immune activation on a background of maternal ID might have more adverse neurodevelopmental consequences for the offspring than exposure to either insult alone. In this study we used this model to determine whether combined exposure to maternal ID and prenatal immune activation interact to affect juvenile and adult behaviors in the offspring. We assessed behaviors relevant to deficits in humans or animals that have been associated with exposure to either maternal ID or prenatal immune activation alone. Adult offspring from ID dams displayed significant deficits in pre-pulse inhibition of acoustic startle and in passive avoidance learning, together with increases in cytochrome oxidase immunohistochemistry, a marker of metabolic activity, in the ventral hippocampus immediately after passive avoidance testing. Offspring from LPS treated dams showed a significant increase in social behavior with unfamiliar rats, and subtle locomotor changes during exploration in an open field and in response to amphetamine. Surprisingly, there was no interaction between effects of the two insults on the behaviors assessed, and few observed alterations in juvenile behavior. Our findings

  8. Effects of neuroleptics administration on adult neurogenesis in the rat hypothalamus.

    PubMed

    Rojczyk, Ewa; Pałasz, Artur; Wiaderkiewicz, Ryszard

    2015-12-01

    Among many factors influencing adult neurogenesis, pharmacological modulation has been broadly studied. It is proven that neuroleptics positively affect new neuron formation in canonical neurogenic sites - subgranular zone of the hippocampal dentate gyrus and subventricular zone of the lateral ventricles. Latest findings suggest that adult neurogenesis also occurs in several additional regions like the hypothalamus, amygdala, neocortex and striatum. As the hypothalamus is considered an important target of neuroleptics, a hypothesis can be made that these substances are able to modulate local neural proliferation. Experiments were performed on adult male rats injected for 28 days or 1 day by three neuroleptics: olanzapine, chlorpromazine and haloperidol. Immunohistochemistry was used to determine expression of proliferation marker (Ki-67) and the marker of neuroblasts - doublecortin (DCX) - which may inform about drug influence on adult neurogenesis at the level of the hypothalamus. It was shown that a single injection of antipsychotics causes significant decrease in hypothalamic DCX expression, but after chronic treatment with chlorpromazine, but not olanzapine, there is an increase in the number of newly formed neuroblasts. Haloperidol has the opposite effect - its long-term administration decreases the number of DCX-positive cells. Cell proliferation levels (Ki-67 expression) increase after long-term drug administration, whereas their single doses do not have any modulatory effect on proliferation potential. Our results throw a new light on the neuroleptics mechanism of action. They also support the potential role of antipsychotics as a factor that can modulate hypothalamic neurogenesis with putative clinical applications. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  9. Adolescent Male Rats Are Less Sensitive than Adults to the Anxiogenic and Serotonin-Releasing Effects of Fenfluramine

    PubMed Central

    Arrant, Andrew E.; Jemal, Hikma; Kuhn, Cynthia M.

    2012-01-01

    Risk taking behavior increases during adolescence, which is also a critical period for the onset of drug abuse. The central serotonergic system matures during the adolescent period, and its immaturity during early adolescence may contribute to adolescent risk taking, as deficits in central serotonergic function have been associated with impulsivity, aggression, and risk taking. We investigated serotonergic modulation of behavior and presynaptic serotonergic function in adult (67–74 days old) and adolescent (28–34 days old) male rats. Fenfluramine (2 mg/kg, i.p.) produced greater anxiogenic effects in adult rats in both the light/dark and elevated plus maze tests for anxiety-like behavior, and stimulated greater increases in extracellular serotonin in the adult medial prefrontal cortex (mPFC) (1, 2.5, and 10 mg/kg, i.p.). Local infusion of 100 mM potassium chloride into the mPFC also stimulated greater serotonin efflux in adult rats. Adult rats had higher tissue serotonin content than adolescents in the prefrontal cortex, amygdala, and hippocampus, but the rate of serotonin synthesis was similar between age groups. Serotonin transporter (SERT) immunoreactivity and SERT radioligand binding were comparable between age groups in all three brain regions. These data suggest that lower tissue serotonin stores in adolescents limit fenfluramine-stimulated serotonin release and so contribute to the lesser anxiogenic effects of fenfluramine. PMID:23103347

  10. Effects of Postnatal Enriched Environment in a Model of Parkinson's Disease in Adult Rats.

    PubMed

    Jungling, Adel; Reglodi, Dora; Karadi, Zsofia Nozomi; Horvath, Gabor; Farkas, Jozsef; Gaszner, Balazs; Tamas, Andrea

    2017-02-14

    Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson's disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life.

  11. Effects of the neonicotinoid insecticide, clothianidin, on the reproductive organ system in adult male rats.

    PubMed

    Bal, Ramazan; Türk, Gaffari; Tuzcu, Mehmet; Yılmaz, Ökkes; Kuloğlu, Tuncay; Baydaş, Gıyasettin; Naziroğlu, Mustafa; Yener, Zabit; Etem, Ebru; Tuzcu, Zeynep

    2013-10-01

    Clothianidin (CTD) is a novel, broad-spectrum insecticide. In the current study, it was aimed to study the effect of subchronic exposure to low doses of CTD (2, 8 and 24 mg/kg body weight/day) on the reproductive system in adult rats. CTD treatment did not significantly change serum testosterone level or sperm parameters (e.g. concentration, motility and morphology), but caused significant decreases in weights of epididymis, right cauda epididymis and seminal vesicles. CTD treatment did not cause sperm DNA fragmentation and did not change the apoptotic index in the seminiferous tubules and levels of α-tocopherol and glutathione, but increased the level of thiobarbituric acid-reactive substances and cholesterol levels significantly at all doses. CTD exposure caused significant elevations in palmitic, linoleic and arachidonic acids in testis in all CTD-exposed groups. There was a drop in 20:4/18:2 (arachidonic acid/linoleic acid) ratio and an increase in 18:1n-9/18:0 (oleic acid/stearic acid) ratios in all CTD groups, in comparison to the control group. In conclusion, CTD had little detectable detrimental effects on the reproductive system of male rats over the measured parameters.

  12. Effect of hindlimb unloading on motor activity in adult rats: impact of prenatal stress.

    PubMed

    Canu, M H; Darnaudéry, M; Falempin, M; Maccari, S; Viltart, O

    2007-02-01

    Environmental changes that occur in daily life or, in particular, in situations like actual or simulated microgravity require neuronal adaptation of sensory and motor functions. Such conditions can exert long-lasting disturbances on an individual's adaptive ability. Additionally, prenatal stress also leads to behavioral and physiological abnormalities in adulthood. Therefore, the aims of the present study were (a) to evaluate in adult rats the behavioral motor adaptation that follows 14 days of exposure to simulated microgravity (hindlimb unloading) and (b) to determine whether restraint prenatal stress influences this motor adaptation. For this purpose, the authors assessed rats' motor reactivity to novelty, their skilled walking on a ladder, and their swimming performance. Results showed that unloading severely impaired motor activity and skilled walking. By contrast, it had no effect on swimming performance. Moreover, results demonstrated for the first time that restraint prenatal stress exacerbates the effects of unloading. These results are consistent with the role of a steady prenatal environment in allowing an adequate development and maturation of sensorimotor systems to generate adapted responses to environmental challenges during adulthood.

  13. Effects of Postnatal Enriched Environment in a Model of Parkinson’s Disease in Adult Rats

    PubMed Central

    Jungling, Adel; Reglodi, Dora; Karadi, Zsofia Nozomi; Horvath, Gabor; Farkas, Jozsef; Gaszner, Balazs; Tamas, Andrea

    2017-01-01

    Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson’s disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life. PMID:28216584

  14. Effects of chronic overload on muscle hypertrophy and mTOR signaling in adult and aged rats

    USDA-ARS?s Scientific Manuscript database

    We examined the effect of 28 days of overload on mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signaling in young adult (Y; 6 mo old) and aged (O; 30 mo old) Fischer 344 x Brown Norway rats subjected to bilateral synergist ablation (SA) of two-thirds of the gas...

  15. Effect of genetically modified corn on the jejunal mucosa of adult male albino rat.

    PubMed

    Ibrahim, Marwa A A; Okasha, Ebtsam F

    2016-11-01

    Genetically modified (GM) plants expressing insecticidal traits offer a new strategy for crop protection. GM-corn contains Bacillus thuringiensis (Bt) genes producing delta endotoxins in the whole plant. Diet can influence the characteristics of the gastrointestinal tract altering its function and structure. The aim of this study was to evaluate the effect of GM-corn on the histological structure of jejunal mucosa of adult male albino rat using different histological, immunohistochemical and morphometrical methods. Twenty adult male albino rats were divided into two equal groups; control and GM-corn fed group administered with 30% GM-corn for 90days. Specimens from the jejunum were processed for light and electron microscopy. Immunohistochemical study was carried out using antibody against proliferating cell nuclear antigen (PCNA). Different morphometrical parameters were assessed. Specimens from GM-corn fed group showed different forms of structural changes. Focal destruction and loss of the villi leaving denuded mucosal surface alternating with stratified areas were observed, while some crypts appeared totally disrupted. Congested blood capillaries and focal infiltration with mononuclear cells were detected. Significant upregulation of PCNA expression, increase in number of goblet cells and a significant increase in both villous height and crypt depth were detected. Marked ultrastructural changes of some enterocytes with focal loss of the microvillous border were observed. Some enterocytes had vacuolated cytoplasm, swollen mitochondria with disrupted cristae and dilated rough endoplasmic reticulum (rER). Some cells had dark irregular nuclei with abnormally clumped chromatin. It could be concluded that consumption of GM-corn profoundly alters the jejunal histological structure. Copyright © 2016 Elsevier GmbH. All rights reserved.

  16. Effect of mesenchymal stem cells on induced skeletal muscle chemodenervation atrophy in adult male albino rats.

    PubMed

    Shehata, Azza S; Al-Ghonemy, Nabila M; Ahmed, Samah M; Mohamed, Samar R

    2017-04-01

    The present research was conducted to evaluate the effect of bone marrow derived mesenchymal stem cells (BM-MSCs) as a potential therapeutic tool for improvement of skeletal muscle recovery after induced chemodenervation atrophy by repeated local injection of botulinum toxin-A in the right tibialis anterior muscle of adult male albino rats. Forty five adult Wistar male albino rats were classified into control and experimental groups. Experimental group was further subdivided into 3 equal subgroups; induced atrophy, BM-MSCs treated and recovery groups. Biochemical analysis of serum LDH, CK and Real-time PCR for Bcl-2, caspase 3 and caspase 9 was measured. Skeletal muscle sections were stained with H and E, Mallory trichrome, and Immunohistochemical reaction for Bax and CD34. Improvement in the skeletal muscle histological structure was noticed in BM-MSCs treated group, however, in the recovery group, some sections showed apparent transverse striations and others still affected. Immunohistochemical reaction of Bax protein showed strong positive immunoreaction in the cytoplasm of muscle fibers in the induced atrophy group. BM-MSCs treated group showed weak positive reaction while the recovery group showed moderate reaction in the cytoplasm of muscle fibers. Immunohistochemical reaction for CD34 revealed occasional positive CD34 stained cells in the induced atrophy group. In BM-MSCs treated group, multiple positive CD34 stained cells were detected. However, recovery group showed some positive CD34 stained cells at the periphery of the muscle fibers. Marked improvement in the regenerative capacity of skeletal muscles after BM-MSCs therapy. Hence, stem cell therapy provides a new hope for patients suffering from myopathies and severe injuries.

  17. Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats

    SciTech Connect

    Krueger, Katharina Repges, Hendrik; Hippler, Joerg; Hartmann, Louise M.; Hirner, Alfred V.; Straub, Heidrun; Binding, Norbert; Musshoff, Ulrich

    2007-11-15

    In this study, the effects of pentavalent dimethylarsinic acid ((CH{sub 3}){sub 2}AsO(OH); DMA{sup V}) and trivalent dimethylarsinous acid ((CH{sub 3}){sub 2}As(OH); DMA{sup III}) on synaptic transmission generated by the excitatory Schaffer collateral-CA1 synapse were tested in hippocampal slices of young (14-21 day-old) and adult (2-4 month-old) rats. Both compounds were applied in concentrations of 1 to 100 {mu}mol/l. DMA{sup V} had no effect on the amplitudes of evoked fEPSPs or the induction of LTP recorded from the CA1 dendritic region either in adult or in young rats. However, application of DMA{sup III} significantly reduced the amplitudes of evoked fEPSPs in a concentration-dependent manner with a total depression following application of 100 {mu}mol/l DMA{sup III} in adult and 10 {mu}mol/l DMA{sup III} in young rats. Moreover, DMA{sup III} significantly affected the LTP-induction. Application of 10 {mu}mol/l DMA{sup III} resulted in a complete failure of the postsynaptic potentiation of the fEPSP amplitudes in slices taken both from adult and young rats. The depressant effect was not reversible after a 30-min washout of the DMA{sup III}. In slices of young rats, the depressant effects of DMA{sup III} were more pronounced than in those taken from adult ones. Compared to the (absent) effect of DMA{sup V} on synaptic transmission, the trivalent compound possesses a considerably higher neurotoxic potential.

  18. Effects of juvenile isolation and morphine treatment on social interactions and opioid receptors in adult rats: behavioural and autoradiographic studies.

    PubMed

    Van den Berg, C L; Van Ree, J M; Spruijt, B M; Kitchen, I

    1999-09-01

    The consequences of juvenile isolation and morphine treatment during the isolation period on (social) behaviour and mu-, delta- and kappa-opioid receptors in adulthood were investigated by using a social interaction test and in vitro autoradiography in rats. Juvenile isolation reduced social exploration in adults. Morphine treatment counteracted this reduction in isolated rats, but decreased social exploration in nonisolated rats. Self-grooming and nonsocial exploration were enhanced after juvenile isolation. Morphine treatment had no effect on self-grooming, but suppressed nonsocial exploration in isolated rats. With respect to the opioid receptors, juvenile isolation resulted in regiospecific increases in mu-binding sites with a 58% increase in the basolateral amygdala and a 33% increase in the bed nucleus of stria terminalis. Morphine treatment in isolated rats reversed this upregulation in both areas. The number of delta-binding sites did not differ between the experimental groups. A general upregulation of kappa-binding sites was observed after juvenile isolation, predominantly in the cortical regions, the hippocampus and the substantia nigra. Morphine treatment did not affect the upregulation of kappa-receptors. The results show that juvenile isolation during the play period causes long-term effects on social and nonsocial behaviours and on the number of mu- and kappa- but not delta-opioid receptors in distinct brain areas. The number of mu-receptors in the basolateral amygdala appears to be negatively correlated with the amount of social exploration in adult rats.

  19. The effect of tannic acid on the bone tissue of adult male Wistar rats exposed to cadmium and lead.

    PubMed

    Tomaszewska, Ewa; Dobrowolski, Piotr; Winiarska-Mieczan, Anna; Kwiecień, Małgorzata; Tomczyk, Agnieszka; Muszyński, Siemowit

    2017-03-02

    Toxic elements such as cadmium (Cd) and lead (Pb) accumulate to the largest extent in bones. Rats at the age of 12 weeks were used to check whether tannic acid (TA) at the concentration of 0.5%, 1.0%, 1.5%. 2.0% or 2.5% would have a protective effect on the structure and properties of bones in the case of exposure to Cd and Pb (diet: 7mg Cd/kg and 50mg Pb/kg) for 12 weeks. The effects of administration of TA in Cd- and Pb-poisoned rats on bone mechanical and geometric properties, trabecular histomorphometry as well as the morphology of articular and growth cartilages were determined. All the rats co-exposured to Cd and Pb had enhanced heavy metals concentration in blood plasma and bone and reduced bone Ca content irrespective of the tannic acid administration. Heave metals given to adult rats did not influence the morphology and geometry of the femur, but reduced the mechanical endurance and histomorphometric parameters of trabecular bone irrespective of the treatment. A diet rich in TA improved articular cartilage and growth plate constituents in heavy metal-poisoned rats, as indicated by the measurement of the thickness of particular zones. It seems that a use of alimentary TA supplementation in adult rats can counteract, in a dose-dependent manner, only some of the destructive changes evoked by Cd and Pb excess.

  20. Effects of thiamine deficiency on food intake and body weight increment in adult female and growing rats.

    PubMed

    Bâ, Abdoulaye

    2012-09-01

    The present study compared the effects of thiamine (vitamin B1) deficiency (TD) on the patterns of food intake and body weight in adult female and neonatal Wistar rats. The adults weighed 250-270 g at the start and were fed for 60 days either with a synthetic TD diet (211 B1) or with the same synthetic diet+thiamine (210 B1). TD led to a marked reduction in food intake and the body weight set point, both recovering rapidly to their initial level in only 3 days after dietetic reversion. The effects of TD in developing rats were evaluated by subjecting pregnant rats to thiamine restriction during different time windows: prenatal (3 days before mating to parturition); perinatal (7 days after mating to the 10th postnatal day); and postnatal (from parturition to weaning). The effect of TD on the occurrence of low birth weight and ponderal growth retardation was examined from postnatal days 1 to 45. Only perinatal TD significantly decreased birth weight relative to untreated or pair-fed controls. Moreover, compared with the control treatments, ponderal growth retardation was not induced by prenatal TD, whereas induction of TD from perinatal into postnatal periods did cause ponderal growth retardation, with long-lasting effects persisting in adulthood. The results suggest a major physiological role of thiamine in the homeostasis of body weight programming, increment, and set point regulation in both offspring and adult female rats.

  1. A comparative study on the effect of high cholesterol diet on the hippocampal CA1 area of adult and aged rats.

    PubMed

    Abo El-Khair, Doaa M; El-Safti, Fatma El-Nabawia A; Nooh, Hanaa Z; El-Mehi, Abeer E

    2014-06-01

    Dementia is one of the most important problems nowadays. Aging is associated with learning and memory impairments. Diet rich in cholesterol has been shown to be detrimental to cognitive performance. This work was carried out to compare the effect of high cholesterol diet on the hippocampus of adult and aged male albino rats. Twenty adult and twenty aged male rats were used in this study. According to age, the rats were randomly subdivided into balanced and high cholesterol diet fed groups. The diet was 15 g/rat/day for adult rats and 20 g/rat/day for aged rats for eight weeks. Serial coronal sections of hippocampus and blood samples were taken from each rat. For diet effect evaluation, Clinical, biochemical, histological, immunohistochemical, and morphometric assessments were done. In compare to a balanced diet fed rat, examination of Cornu Ammonis 1 (CA 1) area in the hippocampus of the high cholesterol diet adult rats showed degeneration, a significant decrease of the pyramidal cells, attenuation and/or thickening of small blood vessels, apparent increase of astrocytes and apparent decrease of Nissl's granules content. Moreover, the high cholesterol diet aged rats showed aggravation of senility changes of the hippocampus together with Alzheimer like pathological changes. In conclusion, the high cholesterol diet has a significant detrimental effect on the hippocampus and aging might pronounce this effect. So, we should direct our attention to limit cholesterol intake in our food to maintain a healthy life style for a successful aging.

  2. Effect of light-dark changes on the locomotor activity in open field in adult rats and opossums.

    PubMed

    Klejbor, I; Ludkiewicz, B; Turlejski, K

    2013-11-01

    There have been no reports on how the light-dark changes determine the locomotor activity of animals in the group of high reactivity (HR) and low reactivity (LR). In the present study we have compared selected parameters of the locomotor activity of the HR and the LR groups of the laboratory opossums and Wistar rats during consecutive, light and dark phases in the open field test. Sixty male Wistar adult rats, at an average weight of 350 g each, and 24 adult Monodelphis opossums of both sexes at an average weight of 120 g each were used. The animals' activity for 2 h daily between the hours of 17:30 and 19:30, in line with the natural light-dark cycle were recorded and then analysed using VideoTrack ver.2.0 (Vievpoint France). According to our results, we noted that a change of the experimental conditions from light to dark involves an increase in the locomotor activity in rats and opossums of the HR group, while there is no effect on the activity of the rats and opossums in the LR group. Locomotor activity in the HR rats, both in the light and dark conditions is characterised by a consistent pattern of change - higher activity in the first stage of the recording and a slowdown (habituation) in the second phase of the observation. The locomotor activity of the opossum, during both light and dark conditions, was observed to be at a consistently high level compared to the rats.

  3. The Ginkgo biloba Extract Reverses the Renal Effects of Titanium Dioxide Nanoparticles in Adult Male Rats

    PubMed Central

    Reynoso-Andeola, Irma Guadalupe; Jaramillo-Juárez, Fernando; Martínez-Ruvalcaba, Haydée; Posadas del Rio, Francisco A.

    2016-01-01

    The Ginkgo biloba extract (GbE) is a commercial product used as a nutraceutic herbal remedy in Europe and US. It contains 27% of the polyphenols isorhamnetin, kaempferol, and quercetin, as antioxidants. We used male adult Wistar rats (200–300 g), divided into four groups: control group (treated with 5.0 mg/kg of sodium chloride, intravenous), titanium dioxide nanoparticles (TiO2-NPs) group (5.0 mg/kg, intravenous), GbE group (10 mg/kg, intraperitoneal), and GbE + TiO2-NPs group (treated 24 h before with 10 mg/kg of GbE, intraperitoneal), followed, 24 h later, by 5.0 mg/kg of TiO2-NPs intravenously. The statistical analysis was performed using Student's t-test for grouped data with ANOVA posttest. The GbE protected renal cells against the effects of TiO2-NPs because it reversed the increased activity of γ-glutamyltranspeptidase and the enzymatic activity of dipeptidylaminopeptidase IV at all times tested (0–5, 5–24, 24–48, and 48–72 h). Also it reversed the glucosuria, hypernatriuria, and urine osmolarity at three times tested (5–24, 24–48, and 48–72). Thus, we conclude that GbE has a beneficial activity in the cytoplasmic membranes of brush border cells on the renal tubules, against the adverse effects that can be produced by some xenobiotics in this case the TiO2-NPs, in experimental rats. PMID:27042354

  4. Effects of a glyphosate-based herbicide on the uterus of adult ovariectomized rats.

    PubMed

    Varayoud, Jorgelina; Durando, Milena; Ramos, Jorge G; Milesi, María M; Ingaramo, Paola I; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2017-04-01

    Glyphosate is the active ingredient of several herbicide formulations. Different reports suggest that glyphosate-based herbicides (GBHs) may act as endocrine disruptors. We evaluated the potential estrogenic effects of a GBH formulation using the uterotrophic assay. Adult ovariectomized rats were sc injected for 3 consecutive days with: saline solution (vehicle control), 2.10(-5)  g E2 /kg/day (uterotrophic dose; UE2 ), 2.10(-7)  g E2 /kg/day (nonuterotrophic dose; NUE2 ), or 0.5, 5, or 50 mg GBH/kg/day of the. Twenty-four hours after the last injection, the uterus was removed and weighed and processed for histopathology and mRNA extraction. Epithelial cell proliferation and height and expression of estrogen-responsive genes were evaluated (estrogen receptors, ERα and ERβ; progesterone receptor, PR; complement 3, C3). Uterine weight and epithelial proliferation were not affected by GBH. However, the luminal epithelial cell height increased at GBH0.5. ERα mRNA was downregulated by all GBH doses and E2 groups, whereas PR and C3 mRNA were diminished by GBH0.5. GBH5-, GBH50-, and UE2 -treated rats showed downregulated ERα protein expression in luminal epithelial cells, while the receptor was upregulated in the stroma. GBH upregulated ERβ (GBH0.5-50) and PR (GBH5) expressions in glandular epithelial cells, similar effect to that of NUE2 group. These results indicate that, although the uterine weight was not affected, GBH modulates the expression of estrogen-sensitive genes. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1191-1201, 2017. © 2016 Wiley Periodicals, Inc.

  5. Effects of NNC 711, a GABA uptake inhibitor, on pentylenetetrazol-induced seizures in developing and adult rats.

    PubMed

    Kubová, H; Haugvicová, R; Mares, P

    1998-09-01

    The anticonvulsant action of NNC 711 [(1-(2-((diphenylmethylene) amino) oxy) ethyl)-1,2,4,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride], an inhibitor of the GABA transporter GAT-1, was studied in a model of pentylenetetrazol-induced motor seizures in rats 7, 12, 18, 25, and 90 days old. NNC 711 at doses of 0.25-20 mg/kg i.p. exhibited two effects in rat pups: a suppression of minimal clonic seizures in age groups in which this type of seizure could be reliably elicited (i.e. in rats aged 18 and 25 days); and a specific suppression or restriction of the tonic phase of generalized tonic-clonic seizures (GTCS) expressed in 18- and especially 12-day-old rats. Effects of NNC 711 on GTCS in 7- and 25-day-old rats were irregular. Adult (i.e. 90-day-old) animals exhibited abolition of generalized tonic-clonic seizures; minimal clonic seizures were suppressed only after substantially higher doses. The abolition of minimal seizures by doses too low to influence generalized tonic-clonic seizures as observed in rat pups is unique among antiepileptic drugs. In addition, an EEG study in rat pups demonstrated dissociation of EEG signs and motor seizures in some animals.

  6. Effects of Extended Exposure to the Antibacterial Triclosan in the the Adult Female Rat

    EPA Science Inventory

    Triclosan (TCS), an antibacterial, has been shown to have endocrine disrupting activity in the rat. We reported previously that TCS advanced puberty in the female rat in the female pubertal assay and potentiated the estrogenic effect of ethinyl estradiol (EE) on uterine growth i...

  7. Behavioral Effects of Sub-Acute Inhalation of Toluene in Adult Rats

    EPA Science Inventory

    Reports of behavioral effects of repeated inhalation of toluene in rats have Yielded inconsistent fmdings. A recent study from this laboratory (Beasley et al., 2010) observed that after 13 weeks of inhaled toluene ("sub-chronic" exposure scenario), rats showed mild but persiste...

  8. Effects of Extended Exposure to the Antibacterial Triclosan in the the Adult Female Rat

    EPA Science Inventory

    Triclosan (TCS), an antibacterial, has been shown to have endocrine disrupting activity in the rat. We reported previously that TCS advanced puberty in the female rat in the female pubertal assay and potentiated the estrogenic effect of ethinyl estradiol (EE) on uterine growth i...

  9. Behavioral Effects of Sub-Acute Inhalation of Toluene in Adult Rats

    EPA Science Inventory

    Reports of behavioral effects of repeated inhalation of toluene in rats have Yielded inconsistent fmdings. A recent study from this laboratory (Beasley et al., 2010) observed that after 13 weeks of inhaled toluene ("sub-chronic" exposure scenario), rats showed mild but persiste...

  10. Effect of "enriched environment" during development on adult rat behavior and response to the dopamine receptor agonist apomorphine.

    PubMed

    Hoffmann, L C; Schütte, S R M; Koch, M; Schwabe, K

    2009-02-18

    Enriched housing conditions (enriched environment, EE) during development has been shown to influence adult rat behavior and transmitter systems, especially dopamine function. We were interested in how different degrees of enrichment during development would affect adult rats' behavior and response to dopamine receptor challenge. Two groups of male Wistar rats (n=11-12) were raised under two different degrees of EE, i.e. "high enriched" and "low enriched" groups. A third group was kept under standard conditions and served as "non-enriched" control. As adults, rats were tested for anxiety (elevated plus-maze), for spatial learning (four-arm-baited eight-arm radial maze), and for motivation (breakpoint of the progressive ratio test). Finally, locomotor activity (activity box) and sensorimotor gating (prepulse inhibition (PPI) of the acoustic startle response (ASR)) were tested with and without challenge with the dopamine receptor agonist apomorphine. The time spent on the open or enclosed arms of the elevated plus-maze did not differ between groups, but the high enriched group showed higher rearing activity on the open arms. The breakpoint did not differ between groups. Learning and memory in the radial maze task only differed on the first few trials, but high enriched rats run faster compared with the other groups. In contrast, in the activity box enriched groups were less active, but apomorphine had the highest effect. Between groups, no difference in PPI and startle amplitude was found, but in the high and low EE group startle amplitude was enhanced after administration of apomorphine, while the PPI deficit induced by this drug was not different between groups. Altogether, we found no evidence that different amounts of environmental enrichment without differences in social EE affect rats' cognitive, emotional or motivational behavior. However, motor activity seems to be enhanced when rats are behaviorally or pharmacologically challenged by dopamine receptor

  11. Prenatal glucocorticoid exposure in rats: programming effects on stress reactivity and cognition in adult offspring.

    PubMed

    Zeng, Yan; Brydges, Nichola M; Wood, Emma R; Drake, Amanda J; Hall, Jeremy

    2015-01-01

    Human epidemiological studies have provided compelling evidence that prenatal exposure to stress is associated with significantly increased risks of developing psychiatric disorders in adulthood. Exposure to excessive maternal glucocorticoids may underlie this fetal programming effect. In the current study, we assessed how prenatal dexamethasone administration during the last week of gestation affects stress reactivity and cognition in adult offspring. Stress reactivity was assessed by evaluating anxiety-like behavior on an elevated plus maze and in an open field. In addition, to characterize the long-term cognitive outcomes of prenatal exposure to glucocorticoids, animals were assessed on two cognitive tasks, a spatial reference memory task with reversal learning and a delayed matching to position (DMTP) task. Our results suggest that prenatal exposure to dexamethasone had no observable effect on anxiety-like behavior, but affected cognition in the adult offspring. Prenatally dexamethasone-exposed animals showed a transient deficit in the spatial reference memory task and a trend to faster acquisition during the reversal-learning phase. Furthermore, prenatally dexamethasone-treated animals also showed faster learning of new platform positions in the DMTP task. These results suggest that fetal overexposure to glucocorticoids programs a phenotype characterized by cognitive flexibility and adaptability to frequent changes in environmental circumstances. This can be viewed as an attempt to increase the fitness of survival in a potentially hazardous postnatal environment, as predicted by intrauterine adversity. Collectively, our data suggest that prenatal exposure to dexamethasone in rats could be used as an animal model for studying some cognitive components of related psychiatric disorders.

  12. Long-term effects of repeated maternal separation and ethanol intake on HPA axis responsiveness in adult rats.

    PubMed

    Odeon, María Mercedes; Yamauchi, Laura; Grosman, Mauricio; Acosta, Gabriela Beatriz

    2017-02-15

    It has been shown that early life manipulations produce behavioral, neural, and hormonal effects. The long term consequences of repeated maternal separation (RMS) plus cold stress and ethanol intake were evaluated during adolescence and adult rats on hypothalamic-pituitary-adrenal (HPA) axis in male adult Wistar rats. RMS+ cold stress was applied from postnatal day (PD) 2 in which the pups were separated from their mothers and exposed to cold stress (4°C) 1h per day for 20days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7days: PD22-29 and PD59-66. Half of the animals were sacrificed, while the others were exposed to acute stress (AS) for 2h and then they were killed. RMS+ cold stress: a) increased voluntary ethanol intake in adolescent and adult rats; b) reduced protein expression (Western measurements) in corticotropin-releasing hormone (CRH) in hypothalamus (Hyp) and mineralocorticoid receptor (MR) in hippocampus (Hic) while increased glucocorticoid receptor (GR) in Hic; c) decreased plasmatic levels of adrenocorticotropic hormone (ACTH) and increased corticosterone (COR) levels in HPA axis, d) adult rats exposure a new AS incremented ACTH and COR levels. However, this modification did not alter the HPA axis capacity to respond to a new type of stressor. These results demonstrate the consequences of early life stress on the vulnerability of ethanol consumption and HPA axis responsiveness to a stressor in adult rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. The effect of elevated plasma phenylalanine levels on protein synthesis rates in adult rat brain.

    PubMed Central

    Dunlop, D S; Yang, X R; Lajtha, A

    1994-01-01

    Increasing the plasma phenylalanine concentration to levels as high as 0.560-0.870 mM (over ten times normal levels) had no detectable effect on the rate of brain protein synthesis in adult rats. The average rates for 7-week-old rats were: valine, 0.58 +/- 0.05%/h, phenylalanine, 0.59 +/- 0.06%/h, and tyrosine, 0.60 +/- 0.09%/h, or 0.59 +/- 0.06%/h overall. Synthesis rates calculated on the basis of the specific activity of the tRNA-bound amino acid were slightly lower (4% lower for phenylalanine) than those based on the brain free amino acid pool. Similarly, the specific activities of valine and phenylalanine in microdialysis fluid from striatum were practically the same as those in the brain free amino acid pool. Thus the specific activities of the valine and phenylalanine brain free pools are good measures of the precursor specific activity for protein synthesis. In any event, synthesis rates, whether based on the specific activities of the amino acids in the brain free pool or those bound to tRNA, were unaffected by elevated levels of plasma phenylalanine. Brain protein synthesis rates measured after the administration of quite large doses of phenylalanine (> 1.5 mumol/g) or valine (15 mumol/g) were in agreement (0.62 +/- 0.01 and 0.65 +/- 0.01%/h respectively) with the rates determined with infusions of trace amounts of amino acids. Thus the technique of stabilizing precursor-specific activity, and pushing values in the brain close to those of the plasma, by the administration of large quantities of precursor, appears to be valid. PMID:8093014

  14. Hippocampal synaptic plasticity: effects of neonatal stress in freely moving adult male rats.

    PubMed

    Petrosino, M; Bronzino, J D; Pizzuti, G P

    1999-01-01

    The present study examines the effects of neonatal isolation on hippocampal LTP in adult male rats. Changes in dentate granule cell population measures, i.e., EPSP slope and population spike amplitude (PSA), evoked by tetanization of the medial perforant pathway were used to assess the effects of neonatal isolation on LTP over a period of 96 h. Following tetanization significant group differences were obtained for input/output (I/O) response measures of EPSP slope and PSA, with isolated males showing consistently higher values than in the other two groups. Comparisons made at 1 h post-tetanization (establishment of LTP) indicated that isolated males showed significantly greater enhancement than any other group. At 96 h (maintenance of LTP), however, neonatally isolated males showed significantly greater enhancement than either non-isolated siblings or unhandled controls. Additionally, isolation resulted in prolonging the duration of enhancement obtained from males. Thus, males show different enhancement profiles with respect to both the magnitude and duration of LTP and neonatal isolation alters these profiles in profound manner.

  15. Effect of selenium on testicular damage induced by varicocele in adult male Wistar rats.

    PubMed

    Taghizadeh, Leila; Eidi, Akram; Mortazavi, Pejman; Rohani, Ali Haeri

    2017-12-01

    Varicocele is an abnormal tortuosity and distension of the veins of the pampiniform plexus in the spermatic cord. It is the most common surgically correctable cause of male infertility. Several studies have revealed the effects of increased oxidative stress on serum, semen, and testicular tissues in patients with varicocele or in animal models. The aim of this study was to investigate the effects of sodium selenite on testicular damage induced by experimental left varicocele in male Wistar rats. In the present study, the effects of oral administration of sodium selenite (at doses of 0.05, 0.1, 0.2, and 0.4mg/kg bw) were assessed in normal and varicocelized rats. The varicocelized control rats showed decrease in sperm quality parameters, decreased activity of testes CAT, GPX and SOD, increased levels of MDA, and damage in testicular architecture. Administration of sodium selenite significantly reduced these changes to nearly normal levels, but did not change these parameters in normal rats. Histopathological studies further confirmed the protective effects of sodium selenite on varicocele-induced testicular damage in rats. Administrations of sodium selenite did not change these parameters in normal rats. Taken together, the results of this study suggest that sodium selenite treatment may have beneficial effect on the testes of varicocelized rats. Copyright © 2017 Elsevier GmbH. All rights reserved.

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

    PubMed

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

    2016-12-01

    Vitamine D (VD) has important functions in the human brain and may play a role in affective-related disorders. VD receptors are expressed in multiple brain regions associated with depressive disorders. The aim of the preclinical study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0mg/kg/day,s.c., once daily, for 14days) on the depression-like behavior and corticosterone levels in the blood samples following ovariectomy in female rats. Cholecalciferol was administered to the ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol (17β-E2, 0.5μg/rat,s.c., once daily, for 14days). Depression-like behavior and spontaneous locomotor activity were assessed in the forced swimming test (FST) and the open field test (OFT), respectively. The corticosterone levels in the blood serum before and after FST were measured in all experimental groups. Treatment with cholecalciferol in high dose (5.0mg/kg/day,s.c.) significantly decreased the immobility time of OVX rats in the FST. Co-administration of cholecalciferol in high dose with 17β-E2 exerted a markedly synergistic antidepressant-like effect in the OVX rats on the same model of depression-like behavior testing. Cholecalciferol in high dose (5.0mg/kg/day,s.c.) administered alone or together with 17β-E2 significantly enhanced frequency of grooming for the OVX rats in the OFT. Moreover, cholecalciferol in high dose administered alone or together with 17β-E2 significantly decreased the elevated corticosterone levels in the blood serum of OVX rats following the FST. These results indicate that Cholecalciferol in high dose has a marked antidepressant-like effect in the adult female rats with low levels of estrogen.

  17. Transplantation of mesenchymal stem cells exerts anti-apoptotic effects in adult rats after spinal cord ischemia-reperfusion injury.

    PubMed

    Yin, Fei; Guo, Li; Meng, Chun-yang; Liu, Ya-juan; Lu, Ri-feng; Li, Peng; Zhou, Yu-bo

    2014-05-02

    It is unknown whether transplantation of bone marrow mesenchymal stem cells (BM-MSCs) can repair spinal cord ischemia-reperfusion injury (SCII) in a rat model through an anti-apoptotic effect. Adult rats were divided into untreated or sham-operated controls, untreated models of SCII (uSCII) and BM-MSC-transplanted models of SCII (tSCII; labeled with CM-Dill transplanted at 1 h and 24 h after reperfusion). According to evaluation of hind-limb motor function, the motor functions of tSCII rats were significantly better than those of uSCII rats by the seventh day. H&E and TUNEL staining showed that the spinal cords of uSCII rats contained damaged neural cells with nuclear pyknosis and congestion of blood vessels, with a high percentage of apoptotic neural cells, while the spinal cords of tSCII rats were nearly normal with significantly fewer apoptotic neural cells. Immunohistochemistry and double immunofluorescence staining revealed that in tSCII rats CASP3 and neurofilament-H (NF-H) levels were 14.57% and 174% those of uSCII rats, respectively, and in tSCII rats the ratio of BAX to BCL2 was reduced by nearly 50%. The differentiation of transplanted CM-Dil-labeled BM-MSCs into neurons and astrocytes was observed in the spinal cords of the tSCII rats under laser scanning confocal microscopy. These results showed that transplantation of BM-MSCs improved functional recovery after SCII via anti-apoptosis.

  18. The Effects of Monosodium Glutamate and Tannic Acid on Adult Rats

    PubMed Central

    Ugur Calis, Ibrahim; Turgut Cosan, Didem; Saydam, Faruk; Kerem Kolac, Umut; Soyocak, Ahu; Kurt, Hulyam; Veysi Gunes, Hasan; Sahinturk, Varol; Sahin Mutlu, Fezan; Ozdemir Koroglu, Zeynep; Degirmenci, Irfan

    2016-01-01

    Background Monosodium glutamate (MSG) is a widely-used flavor enhancer and stabilizer in ready-made or packaged foods. The excessive use of MSG has been shown to increase oxidative stress in different organ systems and causes glucose metabolism disorders, obesity, and coronary diseases. Objectives In this study, the antioxidant activity of tannic acid was investigated experimentally with respect to its protective effects against overdosed MSG-induced oxidative stress in rats. The study took place in Turkey in August 2013. Methods Four groups (n = 7) of three- to four-month-old Sprague-Dawley female rats were used in this study. The first group was the control, who were administered saline. The second group received tannic acid (50 mg/kg, 3 days) intraperitoneally (i.p.). The third group received MSG (2 g/kg, 7 days) i.p., and the fourth group received both tannic acid (50 mg/kg, 3 days, pretreatment) and MSG (2 g/kg, 7 days) i.p. The animals were euthanized ten days later. Blood was collected for determining the hematological values and blood glucose levels. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were determined in the brain, liver, and kidney homogenates, and in the erythrocyte hemolysate. Histopathological examination of the brain, liver, and kidneys was conducted through hematoxylin-eosin staining. Results The data showed that the tannic acid treatment statistically decreased the MDA levels in the brain tissues of the group administered MSG and tannic acid (P < 0.001) when compared to the corresponding values of the control group. The SOD activities in the blood hemolysates of the MSG and tannic acid group increased when compared to the corresponding values for the MSG group (P < 0.01). Additionally, we found that pretreatment with tannic acid reduced blood glucose levels in comparison to the levels of the MSG group (P = 0.029). The results of our study show that tannic acid pretreatment in adult rats decreased blood glucose levels and

  19. Effects of monomethylarsonic and monomethylarsonous acid on evoked synaptic potentials in hippocampal slices of adult and young rats

    SciTech Connect

    Krueger, Katharina Straub, Heidrun; Hirner, Alfred V.; Hippler, Joerg; Binding, Norbert; Musshoff, Ulrich

    2009-04-01

    Arsenite and its metabolites, dimethylarsinic or dimethylarsinous acid, have previously been shown to disturb synaptic transmission in hippocampal slices of rats (Krueger, K., Gruner, J., Madeja, M., Hartmann, L.M., Hirner, A.V., Binding, N., Mu{beta}hoff, U., 2006a. Blockade and enhancement of glutamate receptor responses in Xenopus oocytes by methylated arsenicals. Arch. Toxicol. 80, 492-501, Krueger, K., Straub, H., Binding, N., Mu{beta}hoff, U., 2006b. Effects of arsenite on long-term potentiation in hippocampal slices from adult and young rats. Toxicol. Lett. 165, 167-173, Krueger, K., Repges, H., Hippler, J., Hartmann, L.M., Hirner, A.V., Straub, H., Binding, N., Mu{beta}hoff, U., 2007. Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats. Toxicol. Appl. Pharmacol. 225, 40-46). The present experiments investigate, whether the important arsenic metabolites monomethylarsonic acid (MMA{sup V}) and monomethylarsonous acid (MMA{sup III}) also influence the synaptic functions of the hippocampus. In hippocampal slices of young (14-21 days-old) and adult (2-4 months-old) rats, evoked synaptic field potentials from the Schaffer collateral-CA1 synapse were measured under control conditions and during and after 30 and 60 min of application of the arsenic compounds. MMA{sup V} had no effect on the synapse functions neither in slices of adult nor in those from young rats. However, MMA{sup III} strongly influenced the synaptic transmission: it totally depressed the amplitudes of fEPSPs at concentrations of 50 {mu}mol/l (adult rats) and 25 {mu}mol/l (young rats) and LTP amplitudes at concentrations of 25 {mu}mol/l (adult rats) and 10 {mu}mol/l (young rats), respectively. In contrast, application of 1 {mu}mol/l MMA{sup III} led to an enhancement of the LTP amplitude in young rats, which is interpretable by an enhancing effect on NMDA receptors and a lack of the blocking effect on AMPA receptors at

  20. Effects of monomethylarsonic and monomethylarsonous acid on evoked synaptic potentials in hippocampal slices of adult and young rats.

    PubMed

    Krüger, Katharina; Straub, Heidrun; Hirner, Alfred V; Hippler, Jörg; Binding, Norbert; Musshoff, Ulrich

    2009-04-01

    Arsenite and its metabolites, dimethylarsinic or dimethylarsinous acid, have previously been shown to disturb synaptic transmission in hippocampal slices of rats (Krüger, K., Gruner, J., Madeja, M., Hartmann, L.M., Hirner, A.V., Binding, N., Mubetahoff, U., 2006a. Blockade and enhancement of glutamate receptor responses in Xenopus oocytes by methylated arsenicals. Arch. Toxicol. 80, 492-501, Krüger, K., Straub, H., Binding, N., Mubetahoff, U., 2006b. Effects of arsenite on long-term potentiation in hippocampal slices from adult and young rats. Toxicol. Lett. 165, 167-173, Krüger, K., Repges, H., Hippler, J., Hartmann, L.M., Hirner, A.V., Straub, H., Binding, N., Mubetahoff, U., 2007. Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats. Toxicol. Appl. Pharmacol. 225, 40-46). The present experiments investigate, whether the important arsenic metabolites monomethylarsonic acid (MMA(V)) and monomethylarsonous acid (MMA(III)) also influence the synaptic functions of the hippocampus. In hippocampal slices of young (14-21 days-old) and adult (2-4 months-old) rats, evoked synaptic field potentials from the Schaffer collateral-CA1 synapse were measured under control conditions and during and after 30 and 60 min of application of the arsenic compounds. MMA(V) had no effect on the synapse functions neither in slices of adult nor in those from young rats. However, MMA(III) strongly influenced the synaptic transmission: it totally depressed the amplitudes of fEPSPs at concentrations of 50 micromol/l (adult rats) and 25 micromol/l (young rats) and LTP amplitudes at concentrations of 25 micromol/l (adult rats) and 10 micromol/l (young rats), respectively. In contrast, application of 1 micromol/l MMA(III) led to an enhancement of the LTP amplitude in young rats, which is interpretable by an enhancing effect on NMDA receptors and a lack of the blocking effect on AMPA receptors at this concentration (Kr

  1. Neonatal serotonin reuptake inhibition reduces hypercaloric diet effects on fat mass and hypothalamic gene expression in adult rats.

    PubMed

    Galindo, Lígia Cristina Monteiro; Barros, Manuella da Luz Duarte; Pinheiro, Isabeli Lins; Santana, Ricardo Vinicius de Carvalho; de Matos, Rhowena Jane Barbosa; Leandro, Carol Góis; de Souza, Sandra Lopes; de Castro, Raul Manhães

    2015-11-01

    Serotonin (5-HT) is involved in nervous system ontogenesis, and is important for neurotransmission and behavior modulation after the developmental stage. Alterations in 5-HT levels during the early period of life may signal to feeding behavior and hypothalamic genic expression changes in adulthood. Investigate the effects of hypercaloric diet in adult rats submitted to neonatal serotonin reuptake inhibition on food intake, fat pad mass, plasmatic triglycerides/cholesterol and gene expression of hypothalamic peptides (POMC, NPY) and serotonin receptors (5-HT1B, 5-HT2C). In each litter, 8 pups were divided into two groups: control (C) and fluoxetine (F). From the 1(st) to the 21(st) postnatal day, C pups received sterile saline while F pups received fluoxetine (10mg/kg). From 180 to 215 days, a group of rats from C and F groups were fed hypercaloric diet (CH and FH, 421.4Kcal/100 g) while the rest of animals from C and F groups fed chow diet (CC and FC). The use of hypercaloric diet was associated with lower accumulation of white adipose tissue in adult rats subjected to neonatal serotonin reuptake inhibition. Adult rats of group FC showed decreased 5-HT2C and neuropeptide Y mRNA expression compared with control chow diet group (CC). After chronic use of a hypercaloric diet, the expression of 5-HT2C was higher in the FH group than the FC group and neuropeptide Y expression decreased in FH related to FC. These findings suggest that neonatal serotonin reuptake inhibition is associated with better adaptation to hypercaloric diet in adult rats. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Dose-dependent effect of Bisphenol-A on insulin signaling molecules in cardiac muscle of adult male rat.

    PubMed

    Sivashanmugam, Preethi; Mullainadhan, Vigneswari; Karundevi, Balasubramanian

    2017-03-25

    Environmental contaminant, Bisphenol-A (BPA) is a xenoestrogen, an essential component used for the production of two classes of polymers such as polycarbonate and epoxy resin which disrupts the normal endocrine function. BPA has intense effects on mice endocrine pancreas, an essential tissue involved in glucose metabolism. It disrupts pancreatic β-cell insulin content, induces hyperinsulinemia and insulin resistance in male rats. Cardiac muscle is an insulin responsive organ and insulin has direct effects on glucose transport. The present study was designed to assess the effect of BPA on insulin signaling molecules in the cardiac muscle of adult male Wistar rat. Adult male Wistar rats (200-250 g) were selected and divided into following groups: Group 1: Control (vehicle treated), Group 2: Rats treated with 10 mg BPA/kg b.wt./day for 30 days orally, Group 3: Rats treated with 100 mg BPA/kg b.wt./day for 30 days orally, Group 4: Rats treated with 400 mg BPA/kg b.wt./day for 30 days orally. IR (insulin receptor) and pIR(Tyr1162) proteins were significantly decreased in the high dose group (400 mg). There was no change in IRS1 (insulin receptor substrate-1) and Akt proteins. Whereas, a decrease in pIRS1(Tyr632) (100 mg and 400 mg), pAkt (Ser473) (400 mg) and GLUT4 (glucose transporter 4) (cytosolic and plasma membrane) proteins was observed which may affect the cardiovascular function. It is concluded that BPA exposure has adverse effect on cardiac insulin signal transduction which may affect its function.

  3. Effect of bisphenol A on morphology, apoptosis and proliferation in the resting mammary gland of the adult albino rat.

    PubMed

    Ibrahim, Marwa A A; Elbakry, Reda H; Bayomy, Naglaa A

    2016-02-01

    Bisphenol A (BPA) is a synthetic oestrogen that is extensively used in a wide range of daily used plastic products. This makes it one of the environmental chemicals that may have impact on human health. Due to its oestrogenic effect, BPA might affect the mammary gland. This study aimed to investigate the influence of BPA on the histological structure of the mammary gland of the adult female albino rat and its effect on epithelial cell proliferation and apoptosis status, in addition to its possible modulating effect on estrogen receptor expression. Thirty female adult albino rats were divided into control and experimental groups. The rats in the experimental group were gavaged with 5 mg/kg BPA daily for 8 weeks. The mammary glands were dissected and processed for histological and immunohistochemical stains for Ki-67, activated caspase-3 and estrogen receptor alpha (ER-α). BPA induced an increase in the number and size of the acini and ducts in the mammary gland of treated rats with hyperplasia of their lining epithelial cells. The collagen fibre content was significantly increased in the connective tissue stroma separating the ducts. Immunohistochemical results showed a significant increase in Ki-67 and caspase-3, but a non-significant increase in ER-α expression. Bisphenol A induced structural changes and affected the proliferation rate of mammary glands, so it might be one of the predisposing factors for breast cancer.

  4. Deficient social and play behavior in juvenile and adult rats after neonatal cortical lesion: effects of chronic pubertal cannabinoid treatment.

    PubMed

    Schneider, Miriam; Koch, Michael

    2005-05-01

    The aim of the present study was to investigate the effects of neonatal excitotoxic lesions of the medial prefrontal cortex (mPFC) on social play, social behavior unrelated to play, and self-grooming in juvenile and adult rats. We additionally examined the behavioral effects of chronic pubertal treatment with the cannabinoid agonist WIN 55,212-2 (WIN) in order to test the hypothesis that early lesions render the brain vulnerable to cannabinoid intake in later life. Neonatal mPFC lesions and pubertal WIN treatment disrupted social play, social behavior, and self-grooming in juvenile and adult rats. Additionally, we observed more social play behaviors during light cycle in WIN-treated than in vehicle-treated rats. Notably, the combination of surgery and WIN treatment disrupted social behavior in lesioned and sham-lesioned rats. The present data indicate that the mPFC is important for adequate juvenile response selection in the context of social play and might be involved in the development of adult social and nonsocial behavior. Moreover, our data add further evidence for an involvement of the cannabinoid system in anxiety and social behavior. Additive effects of neonatal surgery-induced stress or cortical lesions in combination with pubertal cannabinoid administration are also shown. The disturbances of social and nonsocial behavior in rats are comparable to symptoms of early frontal cortex damage, as well as neurodevelopmental disorders in humans, such as schizophrenia and autism. Therefore, we propose the combination of neonatal cortical lesions with chronic cannabinoid administration during puberty as an animal model for studying neuronal mechanisms of impaired social functioning in neuropsychiatric disorders.

  5. The effects of prenatal PCBs on adult social behavior in rats

    PubMed Central

    Reilly, Michael P.; Weeks, Connor D.; Topper, Viktoria Y.; Thompson, Lindsay M.; Crews, David; Gore, Andrea C.

    2015-01-01

    Endocrine disrupting chemical (EDC) exposures during critical periods of development may influence neuronal development and the manifestation of sexually dimorphic sociability and social novelty behaviors in adulthood. In this study, we assessed the effects of gestational exposure to PCBs on the social behavior of males and females later in adulthood. A weakly estrogenic PCB mixture, Aroclor 1221 (A1221, 0.5 or 1 mg/kg) was administered to pregnant Sprague-Dawley rat dams. Both a positive control (estradiol benzoate; EB, 50 μg/kg) and negative control (dimethylsulfoxide; DMSO in sesame oil vehicle) were similarly administered to separate sets of dams. The sexes responded differently in two tasks essential to sociality. Using a three-chamber apparatus that contained a caged, same-sex, gonadectomized stimulus animal and an empty stimulus cage, we found that both sexes showed a strong preference for affiliating with a stimulus animal (vs. an empty cage), an effect that was much more pronounced in the males. In the second task, a novel and a familiar stimulus animal were caged at opposite ends of the same apparatus. Females displayed a higher degree of novelty preference than the males. During both tests, females had significantly higher social approach behaviors while male engaged in significantly more interactive behaviors with the conspecific. Of particular interest, males born of dams that received prenatal A1221 (0.5 mg/kg) exhibited an overall decrease in nose-to-nose investigations. These behavioral data suggest that the males are more sensitive to A1221 treatment than are females. In addition to behavioral analysis, serum corticosterone was measured. Females born of dams treated with A1221 (0.5 mg/kg) had significantly higher concentrations of corticosterone than the DMSO female group; males were unaffected. Females also had significantly higher corticosterone concentrations than did males. Overall, our results suggest that the effects of gestational exposure

  6. Enduring behavioural and biochemical effects in the adult rat after prolonged postnatal administration of haloperidol.

    PubMed

    Cuomo, V; Cagiano, R; Coen, E; Mocchetti, I; Cattabeni, F; Racagni, G

    1981-01-01

    Rats were administered 0.5 mg/kg SC of haloperidol (H) or saline (S) daily from day 1 after birth until 20 days of age. At 60 days of age (40 days after the postnatal treatment with H or S was interrupted) the stereotyped behaviour and the effects on locomotor activity elicited by apomorphine in S- and H-pretreated rats were investigated. The intensity of apomorphine (0.5--1 mg/kg, SC)-induced stereotyped behaviour was significantly greater in the H-pretreated group than in S-pretreated animals and this was accompanied by a much more marked reduction of locomotor activity in H-pretreated than in S-pretreated rats. Finally, at 80 days of age (60 days after the postnatal treatment with H or S was interrupted) rats were subjected to a Differential Reinforcement of Low Rates schedule (DRL 15-s). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf less than or equal to 2.5) was significantly more rapid on S-pretreated rats than in H-pretreated ones. In parallel biochemical experiments, acute H produced smaller increases in dopamine turnover in chronic H-treated rats compared with S-treated controls. These data indicate that H treatment in neonatal rats induces behavioural and biochemical changes which can be observed up to 60 days after H withdrawal.

  7. Protective effect of vitamin E on methyl methanesulfonate-induced teratozoospermia in adult Sprague-Dawley rats.

    PubMed

    Tang, Zhian; Ding, Weiliang; Wang, Lun; Jiang, Wenchu; Zhang, Quanxiang; Chen, Hong; Zou, Hongnan; Dong, Yongkang; Shao, Jianwei; Ma, Tieliang

    2015-09-01

    The protective effect of vitamin E (VE, α-tocopherol) on methyl methanesulfonate (MMS)-induced teratozoospermia was investigated in adult rats. Rats (n=6 per group) were divided into three groups: i) Control group, treated with distilled water from days 1 to 5; ii) the MMS group, treated with MMS at a dose of 40 mg·kg(-1) from days 1‑5; or iii) the VE+MMS group, treated with MMS at a dose of 40 mg·kg(-1) from days 1‑5, followed by VE at a dose of 150 mg·kg(-1) from day 6 for 6 weeks. Sperm count, motility and morphology were examined following treatment with VE. The serum testosterone level and antioxidant enzyme activity were measured, and the localization of Vasa, promyelocytic leukemia zinc finger protein (Plzf) and synaptonemal complex protein 3 (Scp3) were also examined. MMS treatment decreased sperm count and motility, and the levels of immunoreactive serum testosterone and endogenous antioxidants. In addition, MMS increased the percentage of abnormal sperm and the levels of free radicals. After MMS and VE treatment, sperm count and motility were significantly higher in rats from the VE+MMS group than in the MMS group. In addition, the serum testosterone concentration, as well as the levels of Vasa and free radicals and the percentage of abnormal sperm, decreased. The results indicated that VE has protective effects against MMS-induced teratozoospermia in adult rats.

  8. Effects of moderate zinc deficiency on cognitive performance in young adult rats.

    PubMed

    Massaro, T F; Mohs, M; Fosmire, G

    1982-07-01

    Two experiments were conducted to establish a dietary zinc level which approximates a moderate deficiency in the young adult rat and to determine if a concurrent zinc deficiency affects cognitive performance. Male rats were fed varying levels of zinc in diet throughout a 17-day period. The lowest dietary level that depressed serum and bone zinc without influencing food consumption or body weight gains was observed to be 5.8 microgram Zn/g diet. Young adult rats maintained on either a zinc adequate (24.4 microgram Zn/g) or low-zinc (5.3 microgram Zn/g) diet were tested in a modified Skinner Box involving tests of visual, auditory, association, and discrimination learning. No differences were observed in the visual discrimination performance of the zinc deficient animals when compared with control counterparts. Deficits in the ability to transfer a learned association between visual and auditory stimuli were observed, however, in the deficient group during the transfer test phase. The latter performed better during the final auditory discrimination task in transferring a learned food-relevant cue.

  9. Attenuated effects of experimenter-administered heroin in adolescent vs. adult male rats: physical withdrawal and locomotor sensitization

    PubMed Central

    Doherty, James M.; Frantz, Kyle J.

    2012-01-01

    Objectives Early onset of heroin use during adolescence might increase chances of later drug addiction. Prior work from our laboratory suggests, however, that adolescent male rats are actually less sensitive than adults to some enduring effects of heroin self-administration. In the present study, we tested two likely correlates of sensitivity to behavioral reinforcement in rats: physical withdrawal and locomotor sensitization. Methods Adolescent (35 days old at start) and adult (79 days old) male Sprague-Dawley rats were administered escalating doses of heroin, increasing from 1.0 to 8.0 mg/kg (i.p.) every 12 hr, across 13 days. Somatic signs of spontaneous withdrawal were scored 12 and 24 hr after the last injection, then every 24 hr for 5 days; locomotion was recorded concurrently. Challenge injections of heroin (1 mg/kg i.p.) were given at 4 points: as the first of the escalating doses (day 1), at days 7 and 13 during the escalating regimen, and after 12 days of forced abstinence. Body mass and food intake were measured throughout experimentation. Results A heroin withdrawal syndrome was not observed among adolescents as it was among adults, including somatic signs as well as reduced locomotion, body mass, and food intake. On the other hand, heroin-induced locomotor sensitization did not differ across ages. Conclusion Reduced withdrawal is consistent with the attenuated reinforcing effects of heroin among adolescent male rats that we reported previously. Thus, it is possible that adolescent rats could reveal important neuroprotective factors for use in treatment of heroin dependence. PMID:22941050

  10. Attenuated effects of experimenter-administered heroin in adolescent vs. adult male rats: physical withdrawal and locomotor sensitization.

    PubMed

    Doherty, James M; Frantz, Kyle J

    2013-02-01

    Early onset of heroin use during adolescence might increase chances of later drug addiction. Prior work from our laboratory suggests, however, that adolescent male rats are actually less sensitive than adults to some enduring effects of heroin self-administration. In the present study, we tested two likely correlates of sensitivity to behavioral reinforcement in rats: physical withdrawal and locomotor sensitization. Adolescent (35 days old at start) and adult (79 days old) male Sprague-Dawley rats were administered escalating doses of heroin, increasing from 1.0 to 8.0 mg/kg (i.p.) every 12 h, across 13 days. Somatic signs of spontaneous withdrawal were scored 12 and 24 h after the last injection, and then every 24 h for 5 days; locomotion was recorded concurrently. Challenge injections of heroin (1 mg/kg i.p.) were given at four points: as the first of the escalating doses (day 1), at days 7 and 13 during the escalating regimen, and after 12 days of forced abstinence. Body mass and food intake were measured throughout experimentation. A heroin withdrawal syndrome was not observed among adolescents as it was among adults, including somatic signs as well as reduced locomotion, body mass, and food intake. On the other hand, heroin-induced locomotor sensitization did not differ across ages. Reduced withdrawal is consistent with the attenuated reinforcing effects of heroin among adolescent male rats that we reported previously. Thus, it is possible that adolescent rats could reveal important neuroprotective factors for use in treatment of heroin dependence.

  11. The effect of methylphenidate and rearing environment on behavioral inhibition in adult male rats

    PubMed Central

    Hill, Jade C.; Covarrubias, Pablo; Terry, Joel; Sanabria, Federico

    2012-01-01

    Rationale The ability to withhold reinforced responses—behavioral inhibition—is impaired in various psychiatric conditions including Attention Deficit Hyperactivity Disorder (ADHD). Methodological and analytical limitations have constrained our understanding of the effects of pharmacological and environmental factors on behavioral inhibition. Objectives To determine the effects of acute methylphenidate (MPH) administration and rearing conditions (isolated vs. pair-housed) on behavioral inhibition in adult rats. Methods Inhibitory capacity was evaluated using two response-withholding tasks, differential reinforcement of low rates (DRL) and fixed minimum interval (FMI) schedules of reinforcement. Both tasks made sugar pellets contingent on intervals longer than 6 s between consecutive responses. Inferences on inhibitory and timing capacities were drawn from the distribution of withholding times (interresponse times, or IRTs). Results MPH increased the number of intervals produced in both tasks. Estimates of behavioral inhibition increased with MPH dose in FMI and with social isolation in DRL. Nonetheless, burst responding in DRL and the divergence of DRL data relative to past studies, among other limitations, undermined the reliability of DRL data as the basis for inferences on behavioral inhibition. Conclusions Inhibitory capacity was more precisely estimated from FMI than from DRL performance. Based on FMI data, MPH, but not a socially enriched environment, appears to improve inhibitory capacity. The highest dose of MPH tested, 8 mg/kg, did not reduce inhibitory capacity but reduced the responsiveness to waiting contingencies. These results support the use of the FMI schedule, complemented with appropriate analytic techniques, for the assessment of behavioral inhibition in animal models. PMID:22057663

  12. Differential Effects of Controllable Stress Exposure on Subsequent Extinction Learning in Adult Rats.

    PubMed

    Hadad-Ophir, Osnat; Brande-Eilat, Noa; Richter-Levin, Gal

    2015-01-01

    Deficits in fear extinction are thought to be related to various anxiety disorders. While failure to extinguish conditioned fear may result in pathological anxiety levels, the ability to quickly and efficiently attenuate learned fear through extinction processes can be extremely beneficial for the individual. One of the factors that may affect the efficiency of the extinction process is prior experience of stressful situations. In the current study, we examined whether exposure to controllable stress, which is suggested to induce stress resilience, can affect subsequent fear extinction. Here, following prolonged two-way shuttle (TWS) avoidance training and a validation of acquired stress controllability, adult rats underwent either cued or contextual fear-conditioning (FC), followed by an extinction session. We further evaluated long lasting alterations of GABAergic targets in the medial pre-frontal cortex (mPFC), as these were implicated in FC and extinction and stress controllability. In cued, but not in contextual fear extinction, within-session extinction was enhanced following controllable stress compared to a control group. Interestingly, impaired extinction recall was detected in both extinction types following the stress procedure. Additionally, stress controllability-dependent alterations in GABAergic markers expression in infralimbic (IL), but not prelimbic (PL) cortex, were detected. These alterations are proposed to be related to the within-session effect, but not the recall impairment. The results emphasize the contribution of prior experience on coping with subsequent stressful experiences. Moreover, the results emphasize that exposure to controllable stress does not generally facilitate future stress coping as previously claimed, but its effects are dependent on specific features of the events taking place.

  13. Differential Effects of Controllable Stress Exposure on Subsequent Extinction Learning in Adult Rats

    PubMed Central

    Hadad-Ophir, Osnat; Brande-Eilat, Noa; Richter-Levin, Gal

    2016-01-01

    Deficits in fear extinction are thought to be related to various anxiety disorders. While failure to extinguish conditioned fear may result in pathological anxiety levels, the ability to quickly and efficiently attenuate learned fear through extinction processes can be extremely beneficial for the individual. One of the factors that may affect the efficiency of the extinction process is prior experience of stressful situations. In the current study, we examined whether exposure to controllable stress, which is suggested to induce stress resilience, can affect subsequent fear extinction. Here, following prolonged two-way shuttle (TWS) avoidance training and a validation of acquired stress controllability, adult rats underwent either cued or contextual fear-conditioning (FC), followed by an extinction session. We further evaluated long lasting alterations of GABAergic targets in the medial pre-frontal cortex (mPFC), as these were implicated in FC and extinction and stress controllability. In cued, but not in contextual fear extinction, within-session extinction was enhanced following controllable stress compared to a control group. Interestingly, impaired extinction recall was detected in both extinction types following the stress procedure. Additionally, stress controllability-dependent alterations in GABAergic markers expression in infralimbic (IL), but not prelimbic (PL) cortex, were detected. These alterations are proposed to be related to the within-session effect, but not the recall impairment. The results emphasize the contribution of prior experience on coping with subsequent stressful experiences. Moreover, the results emphasize that exposure to controllable stress does not generally facilitate future stress coping as previously claimed, but its effects are dependent on specific features of the events taking place. PMID:26793083

  14. Sex differences in the effects of delta9-tetrahydrocannabinol on spatial learning in adolescent and adult rats.

    PubMed

    Cha, Young May; Jones, Katherine H; Kuhn, Cynthia M; Wilson, Wilkie A; Swartzwelder, Harry Scott

    2007-09-01

    Like other recreational drugs, cannabinoids may produce different effects in men and women. In this study we measured the effects of delta9-tetrahydrocannabinol (THC) on spatial learning in two groups that are underrepresented in drug research--females and adolescents. In the first experiment, adolescent (postnatal day 30) and adult (postnatal day 70) rats of both sexes were treated subchronically with 5.0 mg/kg THC or vehicle for five consecutive days. Thirty minutes after each daily injection, they were tested on the spatial version of the Morris water maze task. In the second experiment, a separate group of adolescent and adult rats of both sexes was treated with 5.0 mg/kg THC or vehicle daily for 21 days and tested, 4 weeks later, on the spatial version of the water maze. Subchronic THC impaired spatial learning, and this effect was dependent upon both the age and sex of the animals tested. Prior exposure to chronic THC, however, did not cause any long-lasting spatial learning deficits. On the basis of our previous studies in male rats the third experiment assessed the dose-response relationship for the effects of THC on spatial learning and memory in female animals. We found that subchronic THC treatment (2.5, 5.0, or 10.0 mg/kg, intraperitoneally) disrupted learning in both adolescents and adults, but with greater effects at higher doses in adolescents compared with adults. The developmental sensitivity to subchronic THC confirms previous work carried out in our laboratory, and the sex-dependent effects highlight the importance of including females in drug abuse and addiction research.

  15. Homeostatic regulation of adult hippocampal neurogenesis in aging rats: long-term effects of early exercise

    PubMed Central

    Merkley, Christina M.; Jian, Charles; Mosa, Adam; Tan, Yao-Fang; Wojtowicz, J. Martin

    2014-01-01

    Adult neurogenesis is highly responsive to environmental and physiological factors. The majority of studies to date have examined short-term consequences of enhancing or blocking neurogenesis but long-term changes remain less well understood. Current evidence for age-related declines in neurogenesis warrant further investigation into these long-term changes. In this report we address the hypothesis that early life experience, such as a period of voluntary running in juvenile rats, can alter properties of adult neurogenesis for the remainder of the animal's life. The results indicate that the number of proliferating and differentiating neuronal precursors is not altered in runners beyond the initial weeks post-running, suggesting homeostatic regulation of these processes. However, the rate of neuronal maturation and survival during a 4 week period after cell division was enhanced up to 11 months of age (the end of the study period). This study is the first to show that a transient period of physical activity at a young age promotes changes in neurogenesis that persist over the long-term, which is important for our understanding of the modulation of neurogenesis by exercise with age. Functional integration of adult-born neurons within the hippocampus that resist homeostatic regulation with aging, rather than the absolute number of adult-born neurons, may be an essential feature of adult neurogenesis that promotes the maintenance of neural plasticity in old age. PMID:25071426

  16. EFFECTS OF IN VIVO DECALCIFICATION ON ULTRASTRUCTURE OF ADULT RAT LIVER

    PubMed Central

    Leeson, T. S.; Kalant, H.

    1961-01-01

    A method of in situ perfusion of rat liver via the portal vein is described, by which osmiumtetroxide fixative can be introduced rapidly and uniformly to all parts of the tissue. Previous perfusion with balanced physiological saline solution, under the conditions described, of itself causes minimal change in the liver cell and liver architecture. Perfusion with a chelating agent causes no further detectable alteration within the liver cell but results in separation of the cells, even to the extent of producing a free cell suspension. The separation of cells is not accompanied by any recognizable damage to the plasma membrane but there is a striking tendency to pseudopod formation on the newly exposed surface. These findings provide direct evidence to support the classical concept of the importance of calcium to the adhesiveness of the plasma membrane in the tissues of the adult rat. PMID:13760315

  17. The Effect of a Unilateral Orchiectomy before Gonadotoxic Treatment on the Contralateral Testis in Adult and Prepubertal Rats

    PubMed Central

    Rombaut, Charlotte; Faes, Katrien; Goossens, Ellen

    2016-01-01

    Purpose Previous studies have shown that the removal of one testis leads to a compensatory mechanism in the contralateral one, but this was species and age dependent. The aim of this study was to check whether this compensation would still occur after the combination of a unilateral orchiectomy and gonadotoxic treatment, since this resembles the clinical situation of patients who have to undergo highly toxic cancer treatment and therefore choose to cryopreserve a testicular biopsy for fertility restoration purposes. Materials & Methods Sprague Dawley rats underwent either unilateral orchiectomy, gonadotoxic busulfan treatment, the combination of both or served as fertile control. A comparison of the compensatory effects was made between adult and prepubertal treated rats. Mating experiments were performed, testosterone levels were followed-up, testicular weight was recorded and histology was analysed. Results Adult treated rats were able to restore fertility spontaneously in all treatment groups. On the other hand, 30% of the rats that underwent a unilateral orchiectomy and gonadotoxic treatment at prepubertal age showed hampered spermatogenesis, low testosterone levels, decreased testicular weights and were not able to reproduce. Conclusion This study emphasizes the need of fertility preservation strategies in prepubertal patients before gonadotoxic interventions. PMID:27768736

  18. Effects of dietary alpha- and gamma-linolenic acid on lipid metabolism in young and adult rats.

    PubMed

    Choi, Y S; Sugano, M

    1988-01-01

    The effect of age on lipid metabolism was studied in rats fed diets containing safflower oil (SFO, 78% linoleic acid), evening primrose oil (EPO, 9.4% gamma-linolenic acid and 70% linoleic acid) or the mixture of safflower and linseed oil (SLO, 10.2% alpha-linolenic acid and 68% linoleic acid). The activity of hepatic HMG-CoA reductase declined with age in all groups. In adult rats, the reductase activity was high in the EPO group and low in the SLO group. The activity of hepatic cholesterol 7 alpha-hydroxylase was independent of the diet or age. Hepatic delta 6-desaturase activity was low in adult rats fed EPO. In liver microsomal phospholipids, the percentage of 22:5 n-6 decreased while that of 22:6 n-3 increased with age. The ratio of linoleate metabolites to linoleate was high in the EPO group and low in the SLO group. Liver and serum cholesterol increased with age only in rats fed the SLO diet. Thus, the results indicated an enhanced susceptibility to dietary fats with age.

  19. Long-lasting effects of prenatal dietary choline availability on object recognition memory ability in adult rats.

    PubMed

    Moreno, Hayarelis C; de Brugada, Isabel; Carias, Diamela; Gallo, Milagros

    2013-11-01

    Choline is an essential nutrient required for early development. Previous studies have shown that prenatal choline availability influences adult memory abilities depending on the medial temporal lobe integrity. The relevance of prenatal choline availability on object recognition memory was assessed in adult Wistar rats. Three groups of pregnant Wistar rats were fed from E12 to E18 with choline-deficient (0 g/kg choline chloride), standard (1.1 g/kg choline chloride), or choline-supplemented (5 g/kg choline chloride) diets. The offspring was cross-fostered to rat dams fed a standard diet during pregnancy and tested at the age of 3 months in an object recognition memory task applying retention tests 24 and 48 hours after acquisition. Although no significant differences have been found in the performance of the three groups during the first retention test, the supplemented group exhibited improved memory compared with both the standard and the deficient group in the second retention test, 48 hours after acquisition. In addition, at the second retention test the deficient group did not differ from chance. Taken together, the results support the notion of a long-lasting beneficial effect of prenatal choline supplementation on object recognition memory which is evident when the rats reach adulthood. The results are discussed in terms of their relevance for improving the understanding of the cholinergic involvement in object recognition memory and the implications of the importance of maternal diet for lifelong cognitive abilities.

  20. Effects of maternal nicotine exposure on thyroid hormone metabolism and function in adult rat progeny.

    PubMed

    Lisboa, P C; de Oliveira, E; Manhães, A C; Santos-Silva, A P; Pinheiro, C R; Younes-Rapozo, V; Faustino, L C; Ortiga-Carvalho, T M; Moura, E G

    2015-03-01

    Postnatal nicotine exposure leads to obesity and hypothyroidism in adulthood. We studied the effects of maternal nicotine exposure during lactation on thyroid hormone (TH) metabolism and function in adult offspring. Lactating rats received implants of osmotic minipumps releasing nicotine (NIC, 6 mg/kg per day s.c.) or saline (control) from postnatal days 2 to 16. Offspring were killed at 180 days. We measured types 1 and 2 deiodinase activity and mRNA, mitochondrial α-glycerol-3-phosphate dehydrogenase (mGPD) activity, TH receptor (TR), uncoupling protein 1 (UCP1), hypothalamic TRH, pituitary TSH, and in vitro TRH-stimulated TSH secretion. Expression of deiodinase mRNAs followed the same profile as that of the enzymatic activity. NIC exposure caused lower 5'-D1 and mGPD activities; lower TRβ1 content in liver as well as lower 5'-D1 activity in muscle; and higher 5'-D2 activity in brown adipose tissue (BAT), heart, and testis, which are in accordance with hypothyroidism. Although deiodinase activities were not changed in the hypothalamus, pituitary, and thyroid of NIC offspring, UCP1 expression was lower in BAT. Levels of both TRH and TSH were lower in offspring exposed to NIC, which presented higher basal in vitro TSH secretion, which was not increased in response to TRH. Thus, the hypothyroidism in NIC offspring at adulthood was caused, in part, by in vivo TRH-TSH suppression and lower sensitivity to TRH. Despite the hypothyroid status of peripheral tissues, these animals seem to develop an adaptive mechanism to preserve thyroxine to triiodothyronine conversion in central tissues. © 2015 Society for Endocrinology.

  1. Effects of Anethum graveolens L. (dill) on Oocyte and Fertility of Adult Female Rats

    PubMed Central

    Monsefi, Malihezaman; Ghasemi, Aazam; Alaee, Sanaz; Aliabadi, Elham

    2015-01-01

    Background Our previous studies revealed Anethum graveolens L. caused some changes in female reproductive system that induced infertility. Therefore, in this study, oocyte changes as one of probable reasons of infertility were investigated. Methods In this study, 59 adult female rats were divided into 3 groups of control, low dose (0.5 g/kg) and high dose (5 g/kg) of dill seed aqueous extract (LDE and HDE) treated groups that were gavaged with 1 ml of each dose for 10 days (2 estrous cycles). Vaginal smears were prepared daily. Oocytes of superovulated animals were extracted and their morphometrical changes were measured (n = 5). Oocyte cell membrane glycoconjugates were stained with UEA, PNA, and DBA-FITC lectins (n = 5). Ultrastructural studies of oocytes were performed using TEM (n = 5). The number, weight, and crown-rump length of newborns were examined in three groups after mating with untreated males (n = 5). Data were analyzed using SPSS software. Results Results demonstrated that the duration of the estrous cycle, the diestrus phase and progesterone concentration in the experimental groups increased significantly compared to the control group (p < 0.05). Granulosa cells of corpus luteum in HDE-treated group were larger and clearer. The intensity reactions of galactose/Nacetylgalactoseamine terminal sugar of oocyte decreased insignificantly in experimental groups compared to the control group p > 0.05. Duration of mating to pregnancy increased and the weight and crown-rump length of newborns decreased in experimental groups significantly (p < 0.05). Conclusion Dill seed aqueous extract can induce infertility without any effect on oocyte structure. PMID:25717430

  2. Effects of Anethum graveolens L. (dill) on Oocyte and Fertility of Adult Female Rats.

    PubMed

    Monsefi, Malihezaman; Ghasemi, Aazam; Alaee, Sanaz; Aliabadi, Elham

    2015-01-01

    Our previous studies revealed Anethum graveolens L. caused some changes in female reproductive system that induced infertility. Therefore, in this study, oocyte changes as one of probable reasons of infertility were investigated. In this study, 59 adult female rats were divided into 3 groups of control, low dose (0.5 g/kg) and high dose (5 g/kg) of dill seed aqueous extract (LDE and HDE) treated groups that were gavaged with 1 ml of each dose for 10 days (2 estrous cycles). Vaginal smears were prepared daily. Oocytes of superovulated animals were extracted and their morphometrical changes were measured (n = 5). Oocyte cell membrane glycoconjugates were stained with UEA, PNA, and DBA-FITC lectins (n = 5). Ultrastructural studies of oocytes were performed using TEM (n = 5). The number, weight, and crown-rump length of newborns were examined in three groups after mating with untreated males (n = 5). Data were analyzed using SPSS software. Results demonstrated that the duration of the estrous cycle, the diestrus phase and progesterone concentration in the experimental groups increased significantly compared to the control group (p < 0.05). Granulosa cells of corpus luteum in HDE-treated group were larger and clearer. The intensity reactions of galactose/Nacetylgalactoseamine terminal sugar of oocyte decreased insignificantly in experimental groups compared to the control group p > 0.05. Duration of mating to pregnancy increased and the weight and crown-rump length of newborns decreased in experimental groups significantly (p < 0.05). Dill seed aqueous extract can induce infertility without any effect on oocyte structure.

  3. The effects of simvastatin on ischemia-reperfusion injury of sciatic nerve in adult rats.

    PubMed

    Gholami, Mohammad Reza; Abolhassani, Farid; Pasbakhsh, Parichehr; Akbari, Mohammad; Sobhani, Aligholi; Eshraghian, Mohammad Reza; Kamalian, Naser; Amoli, Fahimeh Asadi; Dehpour, Ahmad Reza; Dehpoor, Ahmad Reza; Sohrabi, Davood

    2008-08-20

    Severe ischemia to nerve results in fiber degeneration and reperfusion results in oxidative injury to endothelial cells and augments fiber degeneration. Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, the most widely used lipid-lowering drugs, have been demonstrated to play a neuroprotective role. So we evaluated the effectiveness of simvastatin in protecting sciatic nerve from ischemia-reperfusion injury using the model of experimental nerve ischemia. Sixty adult male Sprague-Dawley rats weighing 250-300 g were used. They were divided into ten groups (N=6 per group). We used ischemia model in these groups by occluding the femoral artery and vein with a silk suture 6-0 using slipknot technique. All ischemia groups were rendered in ischemic for 3 h reperfused for various times of zero (0 h), 3 h (3 hour reperfusion), 7 days (7 day reperfusion), 14 days (14 day reperfusion). Half of the groups had experimental simvastatin (1 mg/kg) i.v. injection treatment via tail vein 1 h before ischemia. The other half experienced only ischemia-reperfusion as control groups. After euthanasia, histological samples were taken from distal part of the sciatic nerve. Sections were cut at 5 microm and then were stained with H and E and modified trichrome. We used H and E stain for edema and trichrome gomori for ischemic fiber degeneration. Samples were observed to assess their fiber degeneration and edema changes. By observation the level of fiber degeneration and endoneurial edema were also decreased in these recent groups (in both ischemia and reperfusion duration). In conclusion, pre-ischemic administration of simvastatin exhibits neuroprotective properties in ischemia-reperfusion nerve injury.

  4. Early maternal separation has mild effects on cardiac autonomic balance and heart structure in adult male rats.

    PubMed

    Trombini, M; Hulshof, H J; Graiani, G; Carnevali, L; Meerlo, P; Quaini, F; Sgoifo, A

    2012-07-01

    Early life adverse experiences have long-term physiologic and behavioral effects and enhance stress sensitivity. This study examined the effects of maternal separation (MS) on cardiac stress responsivity and structure in adulthood. Male Wistar rats were separated from the dams for 3 h per day from postnatal days 2 through 15. When exposed to 5-day intermittent restraint stress (IRS) as adults, MS, and control rats showed similar acute modifications of cardiac sympathovagal balance, quantified via heart rate variability analysis. In addition, MS had no effect on cardiac pacemaker intrinsic activity (as revealed by autonomic blockade with scopolamine and atenolol) and did not affect the circadian rhythmicity of heart rate, neither before nor after IRS. However, MS differed from control rats in cardiac parasympathetic drive following IRS, which was heightened in the latter but remained unchanged in the former, both during the light and dark phases of the daily rhythm. The evaluation of adult cardiac structure indicated that stress experienced during a crucial developmental period induced only modest changes, involving cardiomyocyte hypertrophy, increased density of vascular structures, and myocardial fibrosis. The mildness of these functional-structural effects questions the validity of MS as a model for early stress-induced cardiac disease in humans.

  5. Effects and Interactions of Tachykinins and Dynorphin on FSH and LH Secretion in Developing and Adult Rats

    PubMed Central

    Ruiz-Pino, F.; Garcia-Galiano, D.; Manfredi-Lozano, M.; Leon, S.; Sánchez-Garrido, M. A.; Roa, J.; Pinilla, L.

    2015-01-01

    Kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which coexpress kisspeptins (Kps), neurokinin B (NKB), and dynorphin (Dyn), regulate gonadotropin secretion. The KNDy model proposes that NKB (a stimulator, through NK3R) and Dyn (an inhibitor, through κ-opioid receptor) shape Kp secretion onto GnRH neurons. However, some aspects of this paradigm remain ill defined. Here we aimed to characterize the following: 1) the effects of NKB signaling on FSH secretion and 2) the role of Dyn in gonadotropin secretion after NK3R activation; 3) additionally, we explored the roles of other tachykinin receptors, NK1R and NK2R, on gonadotropin release. Thus, the effects of the NK3R agonist, senktide, on FSH release were explored across postnatal development in male and female rats; gonadotropin responses to agonists of NK1R substance P and NK2R [neurokinin A (NKA)] were also monitored. Moreover, the effects of senktide on gonadotropin secretion were assessed after antagonizing Dyn actions by nor-binaltorphimine didydrochloride. Before puberty, rats of both sexes showed increased FSH secretion to senktide (and Kp-10). Conversely, adult female rats were irresponsive to senktide in terms of FSH, despite proven LH responses, whereas the adult males did not display FSH or LH responses to senktide, even at high doses. In turn, substance P and NKA stimulated gonadotropin secretion in prepubertal rats, whereas in adults modest gonadotropin responses to NKA were detected. By pretreatment with a Dyn antagonist, adult males became responsive to senktide in terms of LH secretion and displayed elevated basal LH and FSH levels; nor-binaltorphimine didydrochloride treatment uncovered FSH responses to senktide in adult females. Furthermore, the expression of Pdyn and Opkr1 (encoding Dyn and κ-opioid receptor, respectively) in the mediobasal hypothalamus was greater in males than in females at prepubertal ages. Overall, our data contribute to refining our understanding on how the elements of the

  6. Effects and interactions of tachykinins and dynorphin on FSH and LH secretion in developing and adult rats.

    PubMed

    Ruiz-Pino, F; Garcia-Galiano, D; Manfredi-Lozano, M; Leon, S; Sánchez-Garrido, M A; Roa, J; Pinilla, L; Navarro, V M; Tena-Sempere, M

    2015-02-01

    Kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which coexpress kisspeptins (Kps), neurokinin B (NKB), and dynorphin (Dyn), regulate gonadotropin secretion. The KNDy model proposes that NKB (a stimulator, through NK3R) and Dyn (an inhibitor, through κ-opioid receptor) shape Kp secretion onto GnRH neurons. However, some aspects of this paradigm remain ill defined. Here we aimed to characterize the following: 1) the effects of NKB signaling on FSH secretion and 2) the role of Dyn in gonadotropin secretion after NK3R activation; 3) additionally, we explored the roles of other tachykinin receptors, NK1R and NK2R, on gonadotropin release. Thus, the effects of the NK3R agonist, senktide, on FSH release were explored across postnatal development in male and female rats; gonadotropin responses to agonists of NK1R substance P and NK2R [neurokinin A (NKA)] were also monitored. Moreover, the effects of senktide on gonadotropin secretion were assessed after antagonizing Dyn actions by nor-binaltorphimine didydrochloride. Before puberty, rats of both sexes showed increased FSH secretion to senktide (and Kp-10). Conversely, adult female rats were irresponsive to senktide in terms of FSH, despite proven LH responses, whereas the adult males did not display FSH or LH responses to senktide, even at high doses. In turn, substance P and NKA stimulated gonadotropin secretion in prepubertal rats, whereas in adults modest gonadotropin responses to NKA were detected. By pretreatment with a Dyn antagonist, adult males became responsive to senktide in terms of LH secretion and displayed elevated basal LH and FSH levels; nor-binaltorphimine didydrochloride treatment uncovered FSH responses to senktide in adult females. Furthermore, the expression of Pdyn and Opkr1 (encoding Dyn and κ-opioid receptor, respectively) in the mediobasal hypothalamus was greater in males than in females at prepubertal ages. Overall, our data contribute to refining our understanding on how the elements of the

  7. Effect of serotonergic drugs on footshock-induced ultrasonic vocalization in adult male rats.

    PubMed

    Sánchez, C.

    1993-06-01

    Modulation of ultrasonic vocalization (20-30kHz) emitted by adult rats under stressful conditions such as unavoidable foot-shock has been evaluated as a model of anxiety. The effects of 5-HT(1A) receptor agonists with different intrinsic activities and the role of other 5-HT(1) receptor subtypes, and of 5-HT(2) and 5-HT(3) receptors, in mediation of ultrasonic vocalization were studied, as were the effects of increasing serotonergic activity by administration of the 5-HT releaser fenfluramine or the 5-HT precursor 1-5 HTP. The time spent vocalizing 1-6min after four increascapable (1.0mA) footshocks was recorded. Drugs with affinity for 5-HT(1A) receptors (i.e. 8-OHDPAT, flesinoxan, ipsapirone, buspirone, gepirone, NAN-190) abolished the vocalization irrespective of their efficacy. The mixed 5-HT(1) receptor and beta-adrenoceptor antagonists (-)-alprenolol and pindolol inhibited foot-shock-induced ultrasonic vocalization, whereas (-) penbutolol was ineffective. The beta(1)-adrenoceptor antagonist metoprolol and the beta(2)-adrenoceptor antagonist ICI 118.551 were without effect. This suggests that (-)-alprenolol and pindolol act as partial 5-HT(1) agonists in the test model. The non-selective 5-HT(1) receptor agonists eltoprazine, m-CPP and 5-MeODMT and the 5-HT(2) receptor agonists DO1 and d-LSD also abolished the vocalization, whereas the 5-HT(2) receptor antagonist ritanserin and the 5-HT(3) receptor antagonists ondansetron, ICS 205-930 and zacopride were without effect. (-)-Penbutolol reversed 8-OHDPAT-induced inhibition. Ritanserin reversed DOI-induced inhibition of ultrasonic vocalization, but not 8-OHDPAT-induced inhibition. This suggests that there is no functional interaction between 5-HT(1A) and 5-HT(2) receptors in this model. Fenfluramine and 1-5-HTP dose-dependently inhibited footshock-induced ultrasonic vocalization. These findings indicate that the effect most likely is mediated by postsynaptic 5-HT receptors, although contribution by presynaptic 5

  8. Evaluation of possible toxic effects of spearmint (Mentha spicata) on the reproductive system, fertility and number of offspring in adult male rats.

    PubMed

    Nozhat, Fatemeh; Alaee, Sanaz; Behzadi, Khodabakhsh; Azadi Chegini, Najmeh

    2014-11-01

    In this study we investigated the effects of spearmint (Mentha spicata Labiatae) on the reproductive system, fertility and number of offspring in adult male rats. Adult Wistar male rats in one control (C) and three experimental groups (I, II and III) received 0, 10, 20 and 40 mg/kg spearmint extract orally for 45 days, respectively. Following this treatment, the animals' weights, and the standard weight of reproductive tissues, sperm count, sperm motility and serum testosterone concentration were measured, and reproductive tissues were examined histopathologically. To evaluate the effects of spearmint on fertility of male rats and growth of their offspring, male rats of the control and experimental groups mated with untreated female rats. RESULTS showed that spearmint did not affect the rats' body and reproductive tissue weights. The sperm count, fast and slow progressive motility of sperm and serum testosterone concentration decreased while number of non-progressive sperm and immotile sperm increased in the experimental groups compared to the control group, but none of these changes were statistically significant. Histopathological studies showed no severe changes in reproductive tissues between control and experimental groups. Number and growth of offspring born from mating of male rats with untreated female rats showed no difference. We concluded that spearmint has no significant toxic effect on the reproductive system, fertility and number of offspring in adult male rats at the above mentioned dose levels. However high levels of this extract may have adverse effects on male fertility.

  9. Antinociceptive Effects of Spinal Manipulative Therapy on Nociceptive Behavior of Adult Rats during the Formalin Test

    PubMed Central

    Onifer, Stephen M.; Reed, William R.; Sozio, Randall S.; Long, Cynthia R.

    2015-01-01

    Optimizing pain relief resulting from spinal manipulative therapies, including low velocity variable amplitude spinal manipulation (LVVA-SM), requires determining their mechanisms. Pain models that incorporate simulated spinal manipulative therapy treatments are needed for these studies. The antinociceptive effects of a single LVVA-SM treatment on rat nociceptive behavior during the commonly used formalin test were investigated. Dilute formalin was injected subcutaneously into a plantar hindpaw. Licking behavior was video-recorded for 5 minutes. Ten minutes of LVVA-SM at 20° flexion was administered with a custom-made device at the lumbar (L5) vertebra of isoflurane-anesthetized experimental rats (n = 12) beginning 10 minutes after formalin injection. Hindpaw licking was video-recorded for 60 minutes beginning 5 minutes after LVVA-SM. Control rats (n = 12) underwent the same methods except for LVVA-SM. The mean times spent licking the formalin-injected hindpaw of both groups 1–5 minutes after injection were not different. The mean licking time during the first 20 minutes post-LVVA-SM of experimental rats was significantly less than that of control rats (P < 0.001). The mean licking times of both groups during the second and third 20 minutes post-LVVA-SM were not different. Administration of LVVA-SM had a short-term, remote antinociceptive effect similar to clinical findings. Therefore, mechanistic investigations using this experimental approach are warranted. PMID:26693243

  10. The effect of treadmill training on motor recovery after a partial spinal cord compression-injury in the adult rat.

    PubMed

    Multon, Sylvie; Franzen, Rachelle; Poirrier, Anne-Lise; Scholtes, Felix; Schoenen, Jean

    2003-08-01

    Locomotor training on a treadmill is a therapeutic strategy used for several years in human paraplegics in whom it was shown to improve functional recovery mainly after incomplete spinal cord lesions. The precise mechanisms underlying its effects are not known. Experimental studies in adult animals were chiefly performed after complete spinal transections. The objective of this experiment was to assess the effects of early treadmill training on recovery of spontaneous walking capacity after a partial spinal cord lesion in adult rats. Following a compression-injury by a subdurally inflated microballoon, seven rats were trained daily on a treadmill with a body weight support system, whereas six other animals were used as controls and only handled. Spontaneous walking ability in an open field was compared weekly between both groups by two blinded observers, using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. Mean BBB score during 12 weeks was globally significantly greater in the treadmill-trained animals than in the control group, the benefit of training appearing as early as the 2nd week. At week 7, locomotor recovery reached a plateau in both animal groups, but remained superior in trained rats. Daily treadmill training started early after a partial spinal cord lesion in adult rats, which accelerates recovery of locomotion and produces a long-term benefit. These findings in an animal model mimicking the closed spinal cord injury occurring in most human paraplegics are useful for future studies of optimal locomotor training programs, their neurobiologic mechanisms, and their combination with other treatment strategies.

  11. Effects of chronic treatment with methylphenidate on oxidative stress and inflammation in hippocampus of adult rats.

    PubMed

    Motaghinejad, Majid; Motevalian, Manijeh; Shabab, Behnaz

    2016-04-21

    Methylphenidate (MPH) is a central stimulant, prescribed for the treatment of attention deficit/hyperactivity disorder. The long-term behavioral consequences of MPH treatment are unknown. In this study, the oxidative stress and neuroinflammation induced by various doses of MPH were investigated. Forty adult male rats were divided into 5 groups; and treated with different doses of MPH for 21 days. Twenty four hours after drug treatment, Open Field Test (OFT) was performed in all animals. At the end of the study, blood cortisol level (BCL) was measured and hippocampus was isolated and oxidative stress and inflammation parameters and histological changes were analyzed. Chronic MPH at all doses decreased central square entries, number of rearing, ambulation distance and time spent in central square in OFT. BCL increased in doses 10 and 20mg/kg of MPH. Furthermore, MPH in all doses markedly increased lipid peroxidation, mitochondrial oxidized glutathione (GSSG) level, Interleukin 1β (IL-1β) and Tumor Necrosis Factor α (TNF-α) in isolated hippocampus. MPH (10 and 20mg/kg) treated groups had decreased mitochondrial reduced glutathione (GSH) content, and reduced superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRx) activities. 10 and 20mg/kg of MPH change cell density and morphology of cells in Dentate Gyrus (DG) and CA1 areas of hippocampus. Chronic treatment with high doses of MPH can cause oxidative stress, neuroinflammation and neurodegeneration in hippocampus of adult rats.

  12. The effect of gestational ethanol exposure on voluntary ethanol intake in early postnatal and adult rats.

    PubMed

    Youngentob, Steven L; Molina, Juan C; Spear, Norman E; Youngentob, Lisa M

    2007-12-01

    Clinical and epidemiological studies provide strong data for a relationship between prenatal ethanol exposure and the risk for abuse in adolescent and young adult humans. However, drug-acceptance results in response to fetal exposure have differed by study, age at evaluation, and experimental animal. In the present study, the authors tested whether voluntary ethanol intake was enhanced in both the infantile and adult rat (15 and 90 days of age, respectively), as a consequence of chronic fetal drug experience. Experimental rats were exposed in utero by administering ethanol to a pregnant dam in a liquid diet during gestational Days 6-20. Compared with those for isocaloric pair-fed and ad lib chow control animals, the results for experimental animals demonstrated that fetal exposure significantly increased infantile affinity for ethanol ingestion without affecting intake patterns of an alternative fluid (water). Heightened affinity for ethanol was absent in adulthood. Moreover, the results argue against malnutrition as a principal factor underlying the infantile phenomenon. These data add to a growing literature indicative of heightened early postnatal acceptance patterns resulting from maternal use or abuse of ethanol during pregnancy.

  13. No effect of hypergravity on adult rat ventral horn neuron size or SDH activity

    NASA Technical Reports Server (NTRS)

    Roy, R. R.; Ishihara, A.; Moran, M. M.; Wade, C. E.; Edgerton, V. R.

    2001-01-01

    BACKGROUND: Spaceflights of short duration (approximately 2 wk) result in adaptations in the size and/or metabolic properties of a select population of motoneurons located in the lumbosacral region of the rat spinal cord. A decrease in succinate dehydrogenase (SDH, an oxidative marker enzyme) activity of moderately sized (500-800 microm2) motoneurons in the retrodorsolateral region of the spinal cord (L6) has been observed after a 14-d flight. HYPOTHESIS: Our hypothesis was that exposure to short-term hypergravity would result in adaptations in the opposite direction, reflecting a continuum of morphological and biochemical responses in the spinal motoneurons from zero gravity to hypergravity. METHODS: Young, male rats were centrifuged at either 1.5 or 2.0 G for 2 wk. The size and SDH activity of a population of motoneurons in the retrodorsolateral region of the spinal cord (L5) were determined and compared with age-matched rats maintained at 1.0 G. The absolute and relative (to body weight) masses of the soleus, gastrocnemius, adductor longus and tibialis anterior muscles were compared among the three groups. RESULTS: There were no effects of either hypergravity intervention on the motoneuron properties. Rats maintained under hypergravity conditions gained less body mass than rats kept at 1.0 G. For the 1.5 and 2.0 G groups, the muscle absolute mass was smaller and relative mass similar to that observed in the 1.0 G rats, except for the adductor longus. The adductor longus absolute mass was similar to and the relative mass larger in both hypergravity groups than in the 1.0 G group. CONCLUSIONS: Our hypothesis was rejected. The findings suggest that rat motoneurons are more responsive to short-term chronic exposure to spaceflight than to hypergravity conditions.

  14. Effects of isoflurane anesthesia on F-waves in the sciatic nerve of the adult rat.

    PubMed

    Nowicki, Marcin; Baum, Petra; Kosacka, Joanna; Stockinger, Maximilian; Klöting, Nora; Blüher, Matthias; Bechmann, Ingo; Toyka, Klaus V

    2014-08-01

    Nerve conduction studies provide insights into the functional consequences of axonal and myelin pathology in peripheral neuropathies. We investigated whether isoflurane inhalation anesthesia alters F-wave latencies and F-persistence in the sciatic nerve of adult rats. Ten rats were investigated at 3 different isoflurane concentrations followed by ketamine-xylazine injection anesthesia. To assess F-wave latencies, a stimulation paradigm was chosen to minimize H-reflex masking of F-waves. F-wave persistence rates were reduced with 3.5% isoflurane concentration at 4 and 10 Hz supramaximal stimulation and marginally reduced with 2.5% isoflurane when compared with ketamine-xylazine. F-wave amplitudes decreased progressively with rising stimulus frequency in all types of anesthesia and most at 3.5% isoflurane concentration. The type of anesthesia and the stimulus repetition rate have an impact on some F-wave parameters. Higher isoflurane concentrations and repetition rates are not recommended in experimental studies using rat neuropathy models where F-waves are of interest. Copyright © 2013 Wiley Periodicals, Inc.

  15. Gender-Dependent Effects of Enriched Environment and Social Isolation in Ischemic Retinal Lesion in Adult Rats

    PubMed Central

    Kiss, Peter; Szabadfi, Krisztina; Horvath, Gabor; Tamas, Andrea; Farkas, Jozsef; Gabriel, Robert; Reglodi, Dora

    2013-01-01

    Exposure to an enriched environment has been shown to have many positive effects on brain structure and function. Numerous studies have proven that enriched environment can reduce the lesion induced by toxic and traumatic injuries. Impoverished environment, on the other hand, can have deleterious effects on the outcome of neuronal injuries. We have previously shown that enriched conditions have protective effects in retinal injury in newborn rats. It is well-known that the efficacy of neuroprotective strategies can depend on age and gender. The aim of the present study, therefore, was to examine the effects of environmental enrichment and social isolation in retinal ischemia. We used bilateral common carotid artery occlusion to induce retinal hypoperfusion in adult Wistar rats of both genders. Groups were housed in standard, enriched or impoverished conditions. Impoverished environment was induced by social isolation. Retinas were processed for histological analysis after two weeks of survival. In the present study, we show that (1) enriched environment has protective effects in adult ischemic retinal lesion, while (2) impoverished environment further increases the degree of ischemic injury, and (3) that these environmental effects are gender-dependent: females are less responsive to the positive effects of environmental enrichment and more vulnerable to retinal ischemia in social isolation. In summary, our present study shows that the effects of both positive and negative environmental stimuli are gender-dependent in ischemic retinal lesions. PMID:23921682

  16. Effects of testosterone on spatial learning and memory in adult male rats

    PubMed Central

    Spritzer, Mark D.; Daviau, Emily D.; Coneeny, Meagan K.; Engelman, Shannon M.; Prince, W. Tyler; Rodriguez-Wisdom, Karlye N.

    2011-01-01

    A male advantage over females for spatial tasks has been well documented in both humans and rodents, but it remains unclear how the activational effects of testosterone influence spatial ability in males. In a series of experiments, we tested how injections of testosterone influenced the spatial working and reference memory of castrated male rats. In the eight-arm radial maze, testosterone injections (0.500 mg/rat) reduced the number of working memory errors during the early blocks of testing but had no effect on the number of reference memory errors relative to the castrated control group. In a reference memory version of the Morris water maze, injections of a wide range of testosterone doses (0.0625-1.000 mg/rat) reduced path lengths to the hidden platform, indicative of improved spatial learning. This improved learning was independent of testosterone dose, with all treatment groups showing better performance than the castrated control males. Furthermore, this effect was only observed when rats were given testosterone injections starting seven days prior to water maze testing and not when injections were given only on the testing days. We also observed that certain doses of testosterone (0.250 and 1.000 mg/rat) increased perseverative behavior in a reversal-learning task. Finally, testosterone did not have a clear effect on spatial working memory in the Morris water maze, although intermediate doses seemed to optimize performance. Overall, the results indicate that testosterone can have positive activational effects on spatial learning and memory, but the duration of testosterone replacement and the nature of the spatial task modify these effects. PMID:21295035

  17. Nephroprotective effect of date fruit extract against dichloroacetic acid exposure in adult rats.

    PubMed

    El Arem, Amira; Thouri, Amira; Zekri, Mouna; Saafi, Emna Behija; Ghrairi, Fatma; Zakhama, Abdelfattah; Achour, Lotfi

    2014-03-01

    The aim of this study was to investigate the protective effects of aqueous date extract (ADE) on dichloroacetic acid (DCA)-induced nephrotoxicity. In vitro, total phenolic content estimated in the ADE were 417.71mg gallic acid equivalents/100g fresh weights (FW), while total flavonoid and tannins contents were 285.23 and 73.65mg catechin equivalents/100g FW, respectively. The ADE has strong scavenging activity. Ferulic, caffeic and p-coumaric acids are the major's compounds. Nephrotoxicity was induced in male Wistar rats by the administration of 0.5 and 2g/L DCA as drinking water. Some of these rats received also by gavage ADE (4mL/kg) before the administration of DCA. After two months of experiment, DCA administration caused elevated levels of renal MDA, significant depletion of GSH levels, altered the antioxidant enzyme activities and deteriorated the renal functions as assessed by the increased plasma urea, uric acid and creatinine levels compared to control rats. The treatment with the ADE significantly normalized the increased plasma levels of creatinine, urea and uric acid, reduced the elevated MDA levels, significantly normalized the antioxidant enzyme activities and GSH level and restored the altered kidney histology in rats treated with DCA. Therefore, it was speculated that ADE protects rats from kidney damage through its antioxidant capacity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Effects of chronic adult dietary restriction on spatial learning in the aged F344 x BN hybrid F1 rat.

    PubMed

    Fitting, Sylvia; Booze, Rosemarie M; Gilbert, Candace A; Mactutus, Charles F

    2008-02-27

    Dietary restriction (DR) has been shown to increase life span and reduce disease incidence across a variety of species. Recent research suggests that chronic adult DR may also alter age-related cognitive decline. The purpose of this study was twofold: (1) to examine the potential deficits in spatial learning ability in the aged F344 x BN hybrid F1 rat with specific attention to the contributory effects of motoric impairments and (2) to determine the influence of chronic adult DR on any such impairments. The Morris water maze (MWM) task was employed with a 1.8 m diameter tank, 10 cm2 escape platform, 28 degrees C water, and an automated collapsing central starting platform. Spatial learning impairments in the aged rats were evident on all dependent measures during training and the probe test. Motoric function, as reflected in measures of strength and locomotion demonstrated profound age-related performance impairments that were attenuated by chronic adult DR. The present data also replicate previous reports, indicating that DR attenuates the age-related impairments of performance in the MWM as indexed by the latency measure in acquisition, but critically was dissociated from any DR effect on measures of preference and, more critically, accuracy in the probe test. Collectively, the most parsimonious interpretation of DR effects on MWM performance would appear to be the preservation of motoric, and not cognitive, function.

  19. The effects of chronic alcohol consumption and exercise on the skeleton of adult male rats

    NASA Technical Reports Server (NTRS)

    Reed, Adam H.; McCarty, Heidi L.; Evans, Glenda L.; Turner, Russell T.; Westerlind, Kim C.

    2002-01-01

    BACKGROUND: Lifestyle factors are known to affect skeletal development and integrity. Specifically, running has been reported to increase risk of fatigue fractures, whereas chronic alcohol consumption has been shown to reduce bone formation and bone mass. The combined effect of exercise and alcohol on the skeleton has yet to be explored, although alcohol consumption is common among certain physically active populations (e.g., military recruits, college athletes). It was hypothesized that chronic alcohol consumption would accentuate the inherent risk associated with endurance running exercise. METHODS: Six-month-old male Sprague Dawley rats were assigned to one of five groups: baseline, exercise-alcohol diet, exercise-normal diet, sham-alcohol diet, and sham-normal diet. Alcohol-fed rats (35% caloric intake) received a liquid diet ad libitum. Normal animals were pair-fed the identical diet with a maltose dextrin caloric substitute. Exercise was conducted on a motorized treadmill 5 days/wk for 16 weeks. Sham rats were placed on a stationary treadmill for matching time periods. Fluorochrome labels were administered 3 days before baseline and at 10 and 2 days before animals were killed. Heart, soleus, and rectus femoris muscles were wet weighed to assess the effects of training. Tibiae were collected for static and dynamic histomorphometric measurements on cancellous and cortical bone. RESULTS: Muscle weights were larger in the exercised rats versus the sham rats. Alcohol had no significant effect on skeletal muscle weight but did result in larger heart weights in both alcohol-treated groups. Cancellous and periosteal bone formation rates were significantly decreased in the alcohol-fed rats versus rats on the normal diet and were associated with a significant reduction in trabecular thickness in the tibial metaphysis. Cortical and cross-sectional areas were also significantly lower in the alcohol-fed groups compared with the non-alcohol-fed groups. Exercise had no

  20. The effects of chronic alcohol consumption and exercise on the skeleton of adult male rats

    NASA Technical Reports Server (NTRS)

    Reed, Adam H.; McCarty, Heidi L.; Evans, Glenda L.; Turner, Russell T.; Westerlind, Kim C.

    2002-01-01

    BACKGROUND: Lifestyle factors are known to affect skeletal development and integrity. Specifically, running has been reported to increase risk of fatigue fractures, whereas chronic alcohol consumption has been shown to reduce bone formation and bone mass. The combined effect of exercise and alcohol on the skeleton has yet to be explored, although alcohol consumption is common among certain physically active populations (e.g., military recruits, college athletes). It was hypothesized that chronic alcohol consumption would accentuate the inherent risk associated with endurance running exercise. METHODS: Six-month-old male Sprague Dawley rats were assigned to one of five groups: baseline, exercise-alcohol diet, exercise-normal diet, sham-alcohol diet, and sham-normal diet. Alcohol-fed rats (35% caloric intake) received a liquid diet ad libitum. Normal animals were pair-fed the identical diet with a maltose dextrin caloric substitute. Exercise was conducted on a motorized treadmill 5 days/wk for 16 weeks. Sham rats were placed on a stationary treadmill for matching time periods. Fluorochrome labels were administered 3 days before baseline and at 10 and 2 days before animals were killed. Heart, soleus, and rectus femoris muscles were wet weighed to assess the effects of training. Tibiae were collected for static and dynamic histomorphometric measurements on cancellous and cortical bone. RESULTS: Muscle weights were larger in the exercised rats versus the sham rats. Alcohol had no significant effect on skeletal muscle weight but did result in larger heart weights in both alcohol-treated groups. Cancellous and periosteal bone formation rates were significantly decreased in the alcohol-fed rats versus rats on the normal diet and were associated with a significant reduction in trabecular thickness in the tibial metaphysis. Cortical and cross-sectional areas were also significantly lower in the alcohol-fed groups compared with the non-alcohol-fed groups. Exercise had no

  1. Effect of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis in adult rat hippocampus and spatial learning.

    PubMed

    Ueda, S; Sakakibara, S; Yoshimoto, K

    2005-01-01

    The dentate gyrus of the hippocampal formation produces new neurons throughout adulthood in mammalian species. Several experimental statuses and factors regulating to neurogenesis have been identified in the adult dentate gyrus. For example, exposure to an enriched environment enhances neurogenesis in the dentate gyrus and improves hippocampus-dependent spatial learning. Furthermore, serotonin is known to influence adult neurogenesis, and learning and memory. However, the effects of long-lasting depletion of serotonin over the developing period on neurogenesis have not been investigated. Thus, we examined the influence of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis and spatial memory performance. As reported previously, environmental enrichment significantly increased new neurons in the dentate gyrus. However, there was no improvement of the spatial learning test in adult rats in standard and in environmental enrichment housings. Intracisternal administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine, on postnatal day 3 apparently reduced serotonin content in the adult hippocampus without regeneration. This experimental depletion of serotonin in the hippocampus of rats housed in an enriched environment had no effect on spatial memory performance, but produced significant decreases in the number of bromodeoxyuridine-labeled new cells in the dentate gyrus. These findings indicate that newly generated cells stimulated by environmental enrichment are not critical for improvements in hippocampus-dependent learning. Furthermore, numbers of bromodeoxyuridine-labeled cells in the dentate gyrus of 5,7-dihydroxytryptamine-injected rats did not differ between 1 day and 4 weeks after bromodeoxyuridine injection. These data suggest that survival of newly generated dentate gyrus cells remains relatively constant under long-lasting serotonin depletion.

  2. Differential effects of long-term exposure to Aroclor 1254 on lipid secretion by primary cultures of adult rat hepatocytes

    SciTech Connect

    Mendoza-Figueroa, T.; Hernandez, A.; Lopez, L.

    1992-06-01

    PCBs produce hepatic triglyceride (TG) accumulation (fatty liver) in experimental animals and humans exposed accidentally and occupationally. It has been suggested that this effect could be due to a block in TG secretion. On the other hand, increased levels of plasmatic TG and cholesterol have been described in rats after dietary exposure to Aroclor 1254 (Aro) and other PCBs; hypertriglyceridemia and hypertension have been also described in humans exposed for long periods to low concentrations of PCBs. Since the study of hepatic lipid metabolism and its alteration by toxic chemicals is complicated in the whole animal, short term cultures of adult rat hepatocytes have been used. We have described a system for the long term culture of adult rat hepatocytes which for several weeks maintain differentiated functions, like fatty acid and TG synthesis and their export to the culture medium. In this paper we used this culture system to study the effect of long-term exposure to micromolar concentrations of Aro on the secretion of lipids by cultured hepatocytes. 27 refs., 4 figs., 1 tab.

  3. Effects of fasting and/or oxidizing and reducing agents on absorption of neptunium from the gastrointestinal tract of mice and adult or neonatal rats.

    PubMed

    Sullivan, M F; Ruemmler, P S; Ryan, J L

    1984-12-01

    Neptunium-237(V) nitrate was administered by gavage to groups of fed or fasted adult and 5-day-old rats. Some groups also received the oxidants quinhydrone or ferric iron, and others received the reducing agent ferrous iron. Adult mice received ferric or ferrous iron and 235Np. When the adult rats were killed at 7 days after gavage, measurements showed that, compared with rats that were fed, a 24-hr fast caused a fivefold increase in 237Np absorption and retention. Both quinhydrone and ferric iron caused an even greater increase in absorption in both fed and fasted rats. Ferrous iron, on the other hand, decreased absorption in fasted rats to values lower than those obtained in fed rats. Similar results were obtained in mice treated with 235Np and either ferric or ferrous iron. The highest absorption obtained after gavage of ferric iron to fasted rats and mice was about two orders of magnitude higher than the value obtained in animals that were fed before gavage. The effects of ferric and ferrous iron on neptunium absorption by neonatal rats were similar to their effects on adult animals but of lesser magnitude. These results are consistent with the hypothesis that Np(V), when given in small mass quantities to fed animals, is reduced in the gastrointestinal tract to Np(IV), which is less well absorbed than Np(V).

  4. The behavioral effects of chronic sugar and/or caffeine consumption in adult and adolescent rats.

    PubMed

    Franklin, Jane L; Wearne, Travis A; Homewood, Judi; Cornish, Jennifer L

    2017-08-01

    Caffeine is a psychostimulant frequently consumed by adults and children, often in combination with high levels of sugar. Chronic pretreatment with either substance can amplify both amphetamine and cocaine-induced hyperactivity in rodents. The present study sought to elucidate whether age at the time of exposure to sugar and/or caffeine alters sensitivity to an acute illicit psychostimulant (methamphetamine, [METH]) challenge in adulthood. Adult and adolescent (Postnatal Day 35 on first day of treatment) male Sprague-Dawley rats were treated for 26 days with water, caffeine (0.6 g/L), 10% sucrose or their combination. Locomotor behavior was measured on the first and last day of treatment. Following 9-days treatment free, animals were challenged with saline (1 ml/kg, i.p.) or METH (1 mg/kg, i.p.) and locomotor activity was measured. During the treatment period, adolescent rats maintained a higher caffeine (mg/kg) dose than their adult counterparts. Adding sugar to caffeine increased adolescent consumption and the highest caffeine dose consumed was measured in these animals. Drinking sugar-sweetened caffeinated water or combination did not produce cross-sensitization to METH administration in either age group. Nevertheless, the finding that regular exposure through adolescence to caffeinated sugar-sweetened beverages could increase consumption of caffeine and sugar later in life is important, as there is a large body of evidence that has linked excess consumption of sugar-sweetened beverages to a broad range of other negative physical and mental health outcomes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. Histological effects of long term consumption of nutmeg on the medial geniculate body of adult Wistar rats

    PubMed Central

    Adjene, Josiah Obaghwarhievwo; Nwose, Ezekiel Uba

    2010-01-01

    Background: Nutmeg is commonly used as a spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol. The effect of chronic consumption of nutmeg on the medial geniculate body of adult Wistar rats was carefully studied. Aim: The objective is to observe any possible histological changes. Materials and Methods: Rats of both sexes (n = 24), with average weight of 200g were equally and randomly assigned into two treatment groups [A] and [B]; and untreated Control group [C] of (n = 8) per group. The rats in the treatment groups [A] and [B] were respectively given 1g and 2g of nutmeg thoroughly mixed with the feeds on a daily basis for thirty-two days. The control group received equal amount of feeds daily without nutmeg added for the thirty-two days period. All rats were fed with grower's mash and given water liberally. The rats were sacrificed by cervical dislocation method on day thirty-three of the experiment, medial geniculate body was carefully dissected out from the brain and quickly fixed in 10% formol-saline for histological study. Results: The findings indicate that rats in the treated groups (A & B) showed some cellular degenerative changes like hypertrophy, sparse cellular population, pyknotic nuclei with some microcystic changes, and vacuolation in the stroma of the treated medial geniculate body relative to those in the control group. Conclusion: Long term consumption of nutmeg may have adverse effect on microanatomy of medial geniculate body, which could negatively impact on the auditory sensibilities. Further research, including human observational studies, aimed at corroborating these observations is recommended. PMID:22624127

  6. The effect of high-fat--high-fructose diet on skeletal muscle mitochondrial energetics in adult rats.

    PubMed

    Crescenzo, Raffaella; Bianco, Francesca; Coppola, Paola; Mazzoli, Arianna; Cigliano, Luisa; Liverini, Giovanna; Iossa, Susanna

    2015-03-01

    To study the effect of isoenergetic administration to adult rats of high-fat or high-fat--high-fructose diet for 2 weeks on skeletal muscle mitochondrial energetic. Body and skeletal muscle composition, energy balance, plasma lipid profile and glucose tolerance were measured, together with mitochondrial functionality, oxidative stress and antioxidant defense. Rats fed high-fat--high-fructose diet exhibited significantly higher plasma triglycerides and non-esterified fatty acids, together with significantly higher plasma glucose and insulin response to glucose load. Skeletal muscle triglycerides and ceramide were significantly higher in rats fed high-fat--high-fructose diet. Skeletal muscle mitochondrial energetic efficiency and uncoupling protein 3 content were significantly higher, while adenine nucleotide translocase content was significantly lower, in rats fed high-fat or high-fat--high-fructose diet. The results suggest that a high-fat--high-fructose diet even without hyperphagia is able to increase lipid flow to skeletal muscle and mitochondrial energetic efficiency, with two detrimental effects: (a) energy sparing that contributes to the early onset of obesity and (b) reduced oxidation of fatty acids and lipid accumulation in skeletal muscle, which could generate insulin resistance.

  7. Evaluation of possible toxic effects of spearmint (Mentha spicata) on the reproductive system, fertility and number of offspring in adult male rats

    PubMed Central

    Nozhat, Fatemeh; Alaee, Sanaz; Behzadi, Khodabakhsh; Azadi Chegini, Najmeh

    2014-01-01

    Objective: In this study we investigated the effects of spearmint (Mentha spicata Labiatae) on the reproductive system, fertility and number of offspring in adult male rats. Materials and Methods: Adult Wistar male rats in one control (C) and three experimental groups (I, II and III) received 0, 10, 20 and 40 mg/kg spearmint extract orally for 45 days, respectively. Following this treatment, the animals’ weights, and the standard weight of reproductive tissues, sperm count, sperm motility and serum testosterone concentration were measured, and reproductive tissues were examined histopathologically. To evaluate the effects of spearmint on fertility of male rats and growth of their offspring, male rats of the control and experimental groups mated with untreated female rats. Results: Results showed that spearmint did not affect the rats’ body and reproductive tissue weights. The sperm count, fast and slow progressive motility of sperm and serum testosterone concentration decreased while number of non-progressive sperm and immotile sperm increased in the experimental groups compared to the control group, but none of these changes were statistically significant. Histopathological studies showed no severe changes in reproductive tissues between control and experimental groups. Number and growth of offspring born from mating of male rats with untreated female rats showed no difference. Conclusion: We concluded that spearmint has no significant toxic effect on the reproductive system, fertility and number of offspring in adult male rats at the above mentioned dose levels. However high levels of this extract may have adverse effects on male fertility. PMID:25386406

  8. Effects of space flight on the histological characteristics of the aortic depressor nerve in the adult rat: electron microscopic analysis.

    PubMed

    Yamasaki, Masao; Shimizu, Tsuyoshi; Miyake, Masao; Miyamoto, Yukako; Katsuda, Shin-Ichiro; O-Ishi, Hirotaka; Nagayama, Tadanori; Waki, Hidefumi; Katahira, Kiyoaki; Wago, Haruyuki; Okouchi, Toshiyasu; Nagaoka, Shunji; Mukai, Chiaki

    2004-06-01

    The effects of microgravity on the histological characteristics of the aortic depressor nerve, which is the afferent of the aortic baroreflex arc, were determined in 10 female adult rats. The rats were assigned for nursing neonates in the Space Shuttle Columbia or in the animal facility on the ground (NASA Neurolab, STS-90), and were housed for 16 days under microgravity in space (microg, n=5) or under one force of gravity on Earth (one-g, n=5). In the Schwann cell unit in which the axons of unmyelinated fibers are surrounded by one Schwann cell, the average number of axons per unit in the microg group was 2.1 +/- 1.6 (mean +/- SD, n=312) and significantly less than that in the one-g group (3.0 +/- 2.9, n=397, p<0.05). The proportion of unmyelinated fibers in the aortic depressor nerve in the microg group was 64.5 +/- 4.4% and significantly less than that in the one-g group (74.0 +/- 7.3%, p<0.05). These results show that there is a decrease in the number of high-threshold unmyelinated fibers in the aortic depressor nerve in adult rats flown on the Shuttle Orbiter, suggesting that the aortic baroreflex is depressed under microgravity during space flight.

  9. [Effects of TiO₂ nanoparticles on antioxidant function and element content of liver and kidney tissues in young and adult rats].

    PubMed

    Wang, Yun; Chen, Zhang-jian; Ba, Te; Pu, Ji; Cui, Xiao-xing; Jia, Guang

    2014-06-18

    To compare the effect of TiO₂ nanoparticles on antioxidant function and element content of liver and kidney tissues in young and adult rats. Forty-eight SD male rats, half in 4-week (youth) old and half in 9-week (adult) old rats, were randomly divided into 8 groups, which were exposed to TiO₂ nanoparticles [(75 ± 15) nm, anatase] through intragastric administration at 0, 10, 50 and 200 mg/kg body weight every day for 30 days. The liver and kidney tissues were collected for antioxidant function and element content analysis. 200 mg/kg TiO₂ nanoparticles exposure significantly increased the liver total superoxide dismutase (T-SOD) activity and the kidney reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios in young rats, and significantly decreased the liver Mo, Co, Mn and P contents and the kidney Rb and Na contents in young rats. 200 mg/kg TiO₂ nanoparticles exposure significantly increased GSH/GSSG ratios and Rb contents and decreased Na contents in the liver of adult rats. No significantly difference was found in antioxidant indexes and elements content in the kidney of adult rats between three experimental groups and control group. TiO₂ nanoparticles can enhance the antioxidant capacity and decrease the elements content in rat liver and kidney tissues. The liver is the more sensitive target organ and the young animals are more susceptible to TiO₂ nanoparticles toxicity by the oral routes.

  10. Effects of ethanol administration on corticosterone levels in adolescent and adult rats.

    PubMed

    Willey, Amanda Rachel; Anderson, Rachel Ivy; Morales, Melissa; Ramirez, Ruby Liane; Spear, Linda Patia

    2012-02-01

    Adolescent humans and rodents have been shown to consume more alcohol than their adult counterparts. Given that corticosterone (CORT) has been shown to be related to the intake of several drugs of abuse, this study assessed the ontogenetic effects of low-moderate doses of ethanol on CORT increases and recovery. Despite no significant differences in baseline (home cage) CORT levels, CORT responses to ethanol were greater in females than in males and in adult females than in adolescent females; males, however, showed less marked age differences in CORT levels after ethanol consumption. Adolescent blood ethanol concentrations (BECs) were lower than those of adults, although these BEC differences appear insufficient to account for the ontogenetic differences in CORT levels. Collectively, these findings suggest that it is unlikely that age differences in CORT elevations provide a major contribution to the ontogenetic differences in alcohol intake seen between adolescents and adults.

  11. High neuronal/astroglial differentiation plasticity of adult rat hippocampal neural stem/progenitor cells in response to the effects of embryonic and adult cerebrospinal fluids

    PubMed Central

    Peirouvi, T.; Yekani, F.; Azarnia, M.; Massumi, M.

    2015-01-01

    Hippocampal neural stem/progenitor cells (hipp-NS/PCs) of the adult mammalian brain are important sources of neuronal and gial cell production. In this study, the main goal is to investigate the plasticity of these cells in neuronal/astroglial differentiations. To this end, the differentiation of the hipp-NS/PCs isolated from 3-month-old Wistar rats was investigated in response to the embryonic cerebrospinal fluid (E-CSF) including E13.5, E17-CSF and the adult cerebrospinal fluid (A-CSF), all extracted from rats. CSF samples were selected based on their effects on cell behavioral parameters. Primary cell culture was performed in the presence of either normal or high levels of KCL in a culture medium. High levels of KCL cause cell depolarization, and thus the activation of quiescent NSCs. Results from immunocytochemistry (ICC) and semi-quantitative RT-PCR (sRT-PCR) techniques showed that in E-CSF-treated groups, neuronal differentiation increased (E17>E13.5). In contrast, A-CSF decreased and increased neuronal and astroglial differentiations, respectively. Cell survivability and/or proliferation (S/P), evaluated by an MTT assay, increased by E13.5 CSF, but decreased by both E17 CSF and A-CSF. Based on the results, it is finally concluded that adult rat hippocampal proliferative cells are not restricted progenitors but rather show high plasticity in neuronal/astroglial differentiation according to the effects of CSF samples. In addition, using high concentrations of KCL in the primary cell culture led to an increase in the number of NSCs, which in turn resulted in the increase in neuronal or astroglial differentiations after CSF treatment. PMID:27175157

  12. High neuronal/astroglial differentiation plasticity of adult rat hippocampal neural stem/progenitor cells in response to the effects of embryonic and adult cerebrospinal fluids.

    PubMed

    Peirouvi, T; Yekani, F; Azarnia, M; Massumi, M

    2015-01-01

    Hippocampal neural stem/progenitor cells (hipp-NS/PCs) of the adult mammalian brain are important sources of neuronal and gial cell production. In this study, the main goal is to investigate the plasticity of these cells in neuronal/astroglial differentiations. To this end, the differentiation of the hipp-NS/PCs isolated from 3-month-old Wistar rats was investigated in response to the embryonic cerebrospinal fluid (E-CSF) including E13.5, E17-CSF and the adult cerebrospinal fluid (A-CSF), all extracted from rats. CSF samples were selected based on their effects on cell behavioral parameters. Primary cell culture was performed in the presence of either normal or high levels of KCL in a culture medium. High levels of KCL cause cell depolarization, and thus the activation of quiescent NSCs. Results from immunocytochemistry (ICC) and semi-quantitative RT-PCR (sRT-PCR) techniques showed that in E-CSF-treated groups, neuronal differentiation increased (E17>E13.5). In contrast, A-CSF decreased and increased neuronal and astroglial differentiations, respectively. Cell survivability and/or proliferation (S/P), evaluated by an MTT assay, increased by E13.5 CSF, but decreased by both E17 CSF and A-CSF. Based on the results, it is finally concluded that adult rat hippocampal proliferative cells are not restricted progenitors but rather show high plasticity in neuronal/astroglial differentiation according to the effects of CSF samples. In addition, using high concentrations of KCL in the primary cell culture led to an increase in the number of NSCs, which in turn resulted in the increase in neuronal or astroglial differentiations after CSF treatment.

  13. [Effect of the hypothyroidism-castration association on bone and parathyroids from adult female rats].

    PubMed

    Ribeiro, Ana Flávia de C; Serakides, Rogéria; Ocarino, Natália de Melo; Nunes, Vera Alvarenga

    2004-08-01

    The effect of hypothyroidism on bone metabolism and the parathyroids in states of deficiency or sufficiency of sex steroids was studied in 32 two-months-old female Wistar rats distributed in 4 groups of 8 animals each: intact euthyroid (IE), castrated euthyroid (CE), intact hypothyroid (IH) and castrated hypothyroid (CH). After 120 days of treatment, animals were sacrificed and plasma taken to assess free T4. Hyperplasia or hypertrophy of all parathyroids were evident only in IH and CE groups. Of all groups, IH rats presented the most extensive osteopenia, reaching lumbar vertebrae, dental alveolae (jaw and mandible) and long bones. In this group osteopenia resulted from the reduced bone growth, inhibition of bone apposition and return of bone resorption. Although osteopenia in the CH group was almost always more intense in relation to osteopenia presented by CE rats, its intensity was variable when compared to IH rats and dependent on the region studied. Even though it also caused necrosis of higher metabolism bones, the association hypothyroidism-castration did not potentialize the resultant osteopenia of the isolated action of hypothyroidism or castration until 120 days of treatment.

  14. The effects of pomegranate extract on normal adult rat kidney: A stereological study

    PubMed Central

    Mansouri, Esrafil; Basgen, John; Saremy, Sadegh

    2016-01-01

    Pomegranate (Punica granatum L.) has been used widely in the traditional medicine of various civilizations for more than 5000 years. The pomegranate tree has several parts; each part has useful medicinal effects. Previous studies have demonstrated the antibacterial, antioxidant, and anti-inflammatory properties of pomegranate. The aim of the present study was to determine whether administration of pomegranate extract could result in morphometric changes in the kidneys of rats. Eighteen male rats (180-200 g) were divided into three groups that received either: G1, distilled water; G2, 250 mg kg-1 pomegranate extract; and G3, 500 mg kg-1 pomegranate extract via oral gavages daily for eight weeks. At the end of eight weeks, the rats were euthanized and their kidneys were removed and processed for morphometric analyses. In rats received pomegranate extract, the kidney weight, kidney weight/body weight ratio, cortex v/lume and glomerular volume were increased (p < 0.05), while, medulla volume and the number of glomeruli per kidney did not change. No pathological lesions were observed in the kidney. Therefore, pomegranate hydro-alcoholic extract at doses of 250 and 500 (mg kg-1) increased the volume of some parts of the kidney; however, it did not cause any pathological changes in the kidney. PMID:27226880

  15. Comparative effects of X irradiation on the testes of adult Sprague-Dawley and Wistar rats.

    PubMed

    Delic, J I; Schlappack, O K; Harwood, J R; Stanley, J A

    1987-10-01

    The response of the testes of two strains of adult rats (Sprague-Dawley and Wistar) to graded single doses and split doses of 230 kVp X rays has been investigated. A marked difference was noted between the strains in the response of the clonogenic spermatogonia to irradiation, as measured histologically by the repopulation index. Single-dose response curves derived for these cells in the Sprague-Dawley strain had a much larger shoulder (up to about 4-5 Gy) than for the Wistar (less than 2 Gy). Split-dose studies revealed that this difference may partly be explained by a greater repair capacity in the cells of the Sprague-Dawley strain. Changes in serum FSH concentrations mirrored the changes in clonogenic spermatogonial survival following split doses of radiation.

  16. Ethanol-induced effects on opioid peptides in adult male Wistar rats are dependent on early environmental factors.

    PubMed

    Gustafsson, L; Zhou, Q; Nylander, I

    2007-05-25

    The vulnerability to develop alcoholism is dependent on both genetic and environmental factors. The neurobiological mechanisms underlying these factors are not fully understood but individual divergence in the endogenous opioid peptide system may contribute. We have previously reported that early-life experiences can affect endogenous opioids and also adult voluntary ethanol intake. In the present study, this line of research was continued and the effects of long-term voluntary ethanol drinking on the opioid system are described in animals reared in different environmental settings. Rat pups were subjected to 15 min (MS15) or 360 min (MS360) of daily maternal separation during postnatal days 1-21. At 10 weeks of age, male rats were exposed to voluntary ethanol drinking in a four-bottle paradigm with 5%, 10% and 20% ethanol solution in addition to water for 2 months. Age-matched controls received water during the same period. Immunoreactive (ir) Met-enkephalin-Arg6Phe7 (MEAP) and dynorphin B (DYNB) peptide levels were thereafter measured in the pituitary gland and several brain areas. In water-drinking animals, lower ir MEAP levels were observed in the MS360 rats in the hypothalamus, medial prefrontal cortex, striatum and the periaqueductal gray, whereas no differences were seen in ir DYNB levels. Long-term ethanol drinking induced lower ir MEAP levels in MS15 rats in the medial prefrontal cortex and the periaqueductal gray, whereas higher levels were detected in MS360 rats in the hypothalamus, striatum and the substantia nigra. Chronic voluntary drinking affected ir DYNB levels in the pituitary gland, hypothalamus and the substantia nigra, with minor differences between MS15 and MS360. In conclusion, manipulation of the early environment caused changes in the opioid system and a subsequent altered response to ethanol. The altered sensitivity of the opioid peptides to ethanol may contribute to the previously reported differences in ethanol intake between MS15 and MS

  17. Effects of alcohol on pulsatile luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion in the adult male rat

    SciTech Connect

    Badger, T.M.; Abdallah, M.M.; Hayden, J.B. )

    1989-02-09

    To determine possible hypothalamic actions of alcohol on hormone secretion, the effects of acute intragastric alcohol on plasma LH and FSH pulsations were studied. One jugular and one intragastric cannula were surgically implanted into adult male Sprague Dawley rats. Eight days later, rats were bilaterally castrated at 1400 h and infused intragastrically with either saline or 3 g/kg ethanol between 0700 h 0800 h the next days. Blood samples (300 microliters) were collected every 5 min for 3 h (starting at 0800 h), centrifuged and the plasma was frozen for LH and FSH radioimmunoassay. The blood cells were resuspended in saline and returned to the animal immediately following the next sample collection. While the mean plasma LH or FSH concentration did not vary significantly between the alcohol-treated and saline-treated rats, the mean LH (but not FSH) pulse frequency was lower in ethanol-treated rats (3.3 {plus minus} 0.25 pulses/3 h) than saline-treated controls (7.2 {plus minus} 0.3 pulses/3 h). In addition, mean area under the OH pulses were significantly greater in ethanol-treated than saline controls. These data suggest that: (1) ethanol acts to reduce the frequency of LHRH release for the hypothalamus and increase the area under each LH pulse; and (2) LH and FSH secretion are differentially regulated.

  18. Long-term effects of perinatal exposure to low doses of cadmium on the prostate of adult male rats.

    PubMed

    Santana, Viviane P; Salles, Évila S; Correa, Deborah E; Gonçalves, Bianca F; Campos, Silvana G; Justulin, Luiz A; Godinho, Antonio F; Scarano, Wellerson R

    2016-08-01

    Developmental toxicity caused by environmental exposure to heavy metals during the perinatal period has raised questions about offspring health. Cadmium (Cd) is an endocrine-disrupting chemical with the potential to interfere with morphogenesis and susceptibility to diseases in reproductive organs. Taking into account that in the rat prostate morphogenesis occurs during the perinatal period, and that pregnant females absorb and retain more dietary Cd than their non-pregnant counterparts, it is important to understand the effects of perinatal Cd exposure on the adult rat prostate. Therefore this study investigated the effects of gestational and lactational Cd exposure on adult offspring rat prostate histopathology. Pregnant rats (n = 20) were divided into two groups: Control (treated with aqueous solution of sodium acetate 10 mg/l) and treated (treated with aqueous solution of cadmium acetate 10 mg/l) administered in the drinking water. After weaning, male offspring from different litters (n = 10) received food and water 'ad libitum'. The animals were euthanized at postnatal day 90 (PND90), the ventral prostates (VPs) were removed, weighed and examined histopathologically. Blood was collected for the measurement of testosterone (T) levels. Immunohistochemistry for androgen receptor (AR) and Ki67, and a TUNEL assay were performed. There were no differences in T levels, cell proliferation and apoptosis indexes, or AR immunostaining between the experimental groups. Stromal inflammatory foci and multifocal inflammation increased significantly in the treated group. These changes were associated with inflammatory reactive epithelial atypia and stromal fibrillar rearrangement. In conclusion, VP was permanently affected by perinatal Cd exposition, with increased incidence of inflammatory disorders with ageing. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  19. Effects of prolonged alcohol exposure on somatotrophs and corticotrophs in adult rats: Stereological and hormonal study.

    PubMed

    Trifunović, Svetlana; Manojlović-Stojanoski, Milica; Ristić, Nataša; Jurijević, Branka Šošić; Balind, Snežana Raus; Brajković, Gordana; Perčinić-Popovska, Florina; Milošević, Verica

    2016-05-01

    Exposure to alcohol alters many physiological processes, including endocrine status. The present study examined whether prolonged alcohol (A) exposure could modulate selected stereological and hormonal aspects of pituitary somatotrophs (growth hormone-GH cells) and corticotrophs (adrenocorticotropic hormone-ACTH cells) in adult rats. Changes in pituitary gland volume; the volume density, total number and volume of GH and ACTH cells following alcohol exposure were evaluated using a stereological system (newCAST), while peripheral GH and ACTH levels were determined biochemically. Our results demonstrated the reduction (p<0.05) of the volume density (37%) and volume of GH cells (29%) in the group A. Also, there was a tendency for the total number of GH cells to be smaller in the group A. Serum GH level was significantly decreased (p<0.05; 70%) in the group A when compared to control values. Moreover, prolonged alcohol exposure induced declines (p<0.05) in volume density (24%) and volume of ACTH cells (29%). The total number of ACTH cells and ACTH level were higher (p<0.05; 42%) in the group A than in control rats. Collectively, these results indicate that prolonged alcohol exposure leads not only to changes in GH and ACTH hormone levels, but also to alterations of the morphological aspects of GH and ACTH cells within the pituitary.

  20. Distinct effects of repeated restraint stress on basolateral amygdala neuronal membrane properties in resilient adolescent and adult rats.

    PubMed

    Hetzel, Andrea; Rosenkranz, J Amiel

    2014-08-01

    Severe and repeated stress has damaging effects on health, including initiation of depression and anxiety. Stress that occurs during development has long-lasting and particularly damaging effects on emotion. The basolateral amygdala (BLA) plays a key role in many affective behaviors, and repeated stress causes different forms of BLA hyperactivity in adolescent and adult rats. However, the mechanism is not known. Furthermore, not every individual is susceptible to the negative consequences of stress. Differences in the effects of stress on the BLA might contribute to determine whether an individual will be vulnerable or resilient to the effects of stress on emotion. The purpose of this study is to test the cellular underpinnings for age dependency of BLA hyperactivity after stress, and whether protective changes occur in resilient individuals. To test this, the effects of repeated stress on membrane excitability and other membrane properties of BLA principal neurons were compared between adult and adolescent rats, and between vulnerable and resilient rats, using in vitro whole-cell recordings. Vulnerability was defined by adrenal gland weight, and verified by body weight gain after repeated restraint stress, and fecal pellet production during repeated restraint sessions. We found that repeated stress increased the excitability of BLA neurons, but in a manner that depended on age and BLA subnucleus. Furthermore, stress resilience was associated with an opposite pattern of change, with increased slow afterhyperpolarization (AHP) potential, whereas vulnerability was associated with decreased medium AHP. The opposite outcomes in these two populations were further distinguished by differences of anxiety-like behavior in the elevated plus maze that were correlated with BLA neuronal excitability and AHP. These results demonstrate a substrate for BLA hyperactivity after repeated stress, with distinct membrane properties to target, as well as age-dependent factors that

  1. Distinct Effects of Repeated Restraint Stress on Basolateral Amygdala Neuronal Membrane Properties in Resilient Adolescent and Adult Rats

    PubMed Central

    Hetzel, Andrea; Rosenkranz, J Amiel

    2014-01-01

    Severe and repeated stress has damaging effects on health, including initiation of depression and anxiety. Stress that occurs during development has long-lasting and particularly damaging effects on emotion. The basolateral amygdala (BLA) plays a key role in many affective behaviors, and repeated stress causes different forms of BLA hyperactivity in adolescent and adult rats. However, the mechanism is not known. Furthermore, not every individual is susceptible to the negative consequences of stress. Differences in the effects of stress on the BLA might contribute to determine whether an individual will be vulnerable or resilient to the effects of stress on emotion. The purpose of this study is to test the cellular underpinnings for age dependency of BLA hyperactivity after stress, and whether protective changes occur in resilient individuals. To test this, the effects of repeated stress on membrane excitability and other membrane properties of BLA principal neurons were compared between adult and adolescent rats, and between vulnerable and resilient rats, using in vitro whole-cell recordings. Vulnerability was defined by adrenal gland weight, and verified by body weight gain after repeated restraint stress, and fecal pellet production during repeated restraint sessions. We found that repeated stress increased the excitability of BLA neurons, but in a manner that depended on age and BLA subnucleus. Furthermore, stress resilience was associated with an opposite pattern of change, with increased slow afterhyperpolarization (AHP) potential, whereas vulnerability was associated with decreased medium AHP. The opposite outcomes in these two populations were further distinguished by differences of anxiety-like behavior in the elevated plus maze that were correlated with BLA neuronal excitability and AHP. These results demonstrate a substrate for BLA hyperactivity after repeated stress, with distinct membrane properties to target, as well as age-dependent factors that

  2. Effects of metoclopramide on mRNA levels of steroid 5α-reductase isozymes in prostate of adult rats.

    PubMed

    Sánchez, Pilar; Torres, Jesús M; Castro, Beatriz; Frías, José F; Ortega, Esperanza

    2013-03-01

    The rising incidence of prostate cancer and benign prostatic hypertrophy in the Western world is a cause of increasing public health concern. The most active androgen in the prostate is 5α-dihydrotestosterone obtained from testosterone (T) by the enzyme 5α-reductase (5α-R), expressed in the prostate as two isozymes, 5α-R1 and 5α-R2. These isozymes are involved in the growth and development of normal prostate and in the onset and progression of prostate disease. Besides androgens, prolactin (PRL) may also play a role, although it is not clear whether its effects on the prostate are in synergism with or independent of those of androgens. We previously demonstrated that sulpiride, an inductor of hyperprolactinemia, increased mRNA levels of 5α-R isozymes in prostate of adult rat. We hypothesized a possible interrelationship between PRL levels and 5α-R, although the effects of sulpiride per se cannot be ruled out. In the present study, one-step quantitative reverse transcription polymerase chain reaction coupled with laser-induced fluorescence capillary electrophoresis was used to quantify mRNA levels of both 5α-R isozymes in prostate of adult rat after administration of metoclopramide (MTC), another inductor of PRL secretion. With the administration regimens studied, MTC produced an increase in prostate weight and mRNA levels of 5α-R1 and 5α-R2 in adult rats. Given our finding that MTC per se or MTC-induced hyperprolactinemia modifies prostate disease-related parameters in animals with reduced plasma T levels, further investigation is warranted into the possibility that MTC use by aging males may increase their risk of prostate disease.

  3. The protective effect of omega-3 oil against the hepatotoxicity of cadmium chloride in adult and weanling rats

    NASA Astrophysics Data System (ADS)

    Ismail, Treefa F.; Aziz, Falah M.

    2017-09-01

    The purpose of the present study was to investigate the protective role of omega-3 oil against the toxic effect of cadmium as cadmium chloride (CdCl2) on the liver of male, dams and weanling rats from the histological, ultrastructural and immunohistochemical points of view. Thirty adult male and thirty adult female rats (dams) were used in the present work, divided randomly into five groups, six rats for each group and ten weanling male rats were chosen from each dam group. First group was considered as control group and given only standard diet and drinking water, second group was given (40 mg/ L) of CdCl2 in drinking water. The third group was given (60 mg/ L) of CdCl2 in drinking water. The fourth group was given (40 mg/L) of CdCl2 in drinking water plus omega-3 oil (4 gm/ kg diet) and the fifth group was given (60 mg/L) of CdCl2 in drinking water plus omega-3 oil (4 gm/ kg diet). All the above groups were left for 30 days for males and 42 days for the females) i.e. at the 21th day of the weanling rats birth). Both doses of CdCl2 have caused a lot of histological and ultrastructural alterations in the liver including high degeneration of hepatocytes. Electron microscope images showed thickening of mitochondrial membrane, variation in the size and shape of the mitochondria of the above cells and deposition of Cd particles in the lining of blood sinusoids. The hepatocytes of the weanling rats showed more ultrastructural changes especially the accumulation of lipid droplets. The immunohistochemical images of the mother liver showed a positive P53 reaction in the cells of the liver of CdCl2 treated rats especially those around the portal area. These reactions disappeared in the omega-3 plus CdCl2 groups. The present results suggested a protective role of omega-3 against the cadmium induced hepatotoxicity.

  4. Chronic Δ9-Tetrahydrocannabinol during Adolescence Differentially Modulates Striatal CB1 Receptor Expression and the Acute and Chronic Effects on Learning in Adult Rats.

    PubMed

    Weed, Peter F; Filipeanu, Catalin M; Ketchum, Myles J; Winsauer, Peter J

    2016-01-01

    The purpose of this study was to determine whether chronic administration of Δ(9)-tetrahydrocannabinol (THC) during adolescence would (1) modify any sex-specific effects of THC on learning and (2) affect the development of tolerance to THC as an adult. Male and female rats received daily injections of saline or 5.6 mg/kg of THC from postnatal day 35-75, yielding four groups (female/saline, female/THC, male/saline, and male/THC). Rats were then trained on a procedure that assayed both learning and performance behavior and administered 0.32-18 mg/kg of THC acutely as adults (experiment 1). THC produced rate-decreasing and error-increasing effects in both sexes; however, female rats were more sensitive than male rats were to the rate-decreasing effects. Rats were then chronically administered 10 mg/kg of THC (experiment 2). Rats that received THC during adolescence developed tolerance to the rate-decreasing effects more slowly and less completely than did rats that received saline; in addition, females developed tolerance to the error-increasing effects of THC slower than males did. Western blot analysis of brain tissue indicated long-term changes in hippocampal and striatal cannabinoid type-1 receptor (CB1R) levels despite levels that were indistinguishable immediately after chronic treatment during adolescence. Striatal CB1R levels were increased in adult rats that received THC during adolescence; hippocampal CB1R levels varied by sex. In summary, female rats were more sensitive than male rats were to the acute and chronic effects of THC, and chronic administration of THC during adolescence produced long-term changes in CB1R levels that correlated with decreased tolerance development to the rate-decreasing effects of THC.

  5. Assessment of the effects of sex and sex hormones on spatial cognition in adult rats using the Barnes maze.

    PubMed

    Locklear, M N; Kritzer, M F

    2014-07-01

    Although sex differences and hormone effects on spatial cognition are observed in humans and animals, consensus has not been reached regarding exact impact on spatial working or reference memory. Recent studies in rats suggest that stress and/or reward, which are often different in tasks used to assess spatial cognition, can contribute to the inconsistencies in the literature. To minimize the impact of these sex- and sex hormone-sensitive factors, we used the Barnes maze to compare spatial working memory, spatial reference memory and spatial learning strategy in adult male, female, gonadectomized (GDX) male, and GDX male rats supplemented with 17β-estradiol (E) or testosterone propionate (TP). Rats received four acquisition trials, four trials 24h later, and a single retention trial one week after. Males and females acquired the task during the first four trials and retained the task thereafter. In contrast, GDX rats took longer to acquire the task and showed retention deficits at 1week. All deficits were attenuated similarly by TP and E. Assessment of search patterns also showed that strategies in the males transitioned from random to spatially focused and eventually direct approaches to the goal. However, this transition was faster in control and GDX-TP than in GDX and GDX-E rats. In contrast, the females almost invariantly followed the maze edge in thigmotactic, serial searches. Thus, while Barnes maze reveals activational, in part estrogenic effects on spatial cognition in males, its amenability to animals' use of multiple strategies may limit its ability to resolve mnemonic differences across sex. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Assessment of the effects of sex and sex hormones on spatial cognition in adult rats using the Barnes maze

    PubMed Central

    Locklear, MN; Kritzer, MF

    2014-01-01

    Although sex differences and hormone effects on spatial cognition are observed in humans and animals, consensus has not been reached regarding exact impact on spatial working or reference memory. Recent studies in rats suggest that stress and/or reward, which are often different in tasks used to assess spatial cognition, can contribute to the inconsistencies in the literature. To minimize the impact of these sex- and sex hormone-sensitive factors, we used the Barnes maze to compare spatial working memory, spatial reference memory and spatial learning strategy in adult male, female, gonadectomized (GDX) male, and GDX male rats supplemented with 17β-estradiol (E) or testosterone propionate (TP). Rats received four acquisition trials, four trials 24 h later, and a single retention trial one week after. Males and females acquired the task during the first four trials and retained the task thereafter. In contrast, GDX rats took longer to acquire the task and showed retention deficits at 1 week. All deficits were attenuated similarly by TP and E. Assessment of search patterns also showed that strategies in the males transitioned from random to spatially focused and eventually direct approaches to the goal. However, this transition was faster in control and GDX-TP than in GDX and GDX-E rats. In contrast, the females almost invariantly followed the maze edge in thigmotactic, serial searches. Thus, while Barnes maze reveals activational, in part estrogenic effects on spatial cognition in males, its amenability to animals' use of multiple strategies may limit its ability to resolve mnemonic differences across sex. PMID:24937438

  7. EFFECTS ON BIRTH WEIGHT AND ADULT HEALTH IN RATS PRENATALLY EXPOSED TO TOXICANTS OR UNDERNUTRITION

    EPA Science Inventory

    Low fetal weight is a sensitive indicator of developmental toxicity in animal studies. While low birth weight may be permanent or transitory, the long-term effects of low birth weight on adult health have not been elucidated. Previous research has shown in humans an inverse rela...

  8. EFFECTS ON BIRTH WEIGHT AND ADULT HEALTH IN RATS PRENATALLY EXPOSED TO TOXICANTS OR UNDERNUTRITION

    EPA Science Inventory

    Low fetal weight is a sensitive indicator of developmental toxicity in animal studies. While low birth weight may be permanent or transitory, the long-term effects of low birth weight on adult health have not been elucidated. Previous research has shown in humans an inverse rela...

  9. Effects of caloric restriction on nitrogen and carbon stable isotope ratios in adult rat bone.

    PubMed

    Robertson, Kimberly L; Rowland, Neil E; Krigbaum, John

    2014-10-15

    Stable isotope analysis is a valuable technique for dietary estimation in ecological and archaeological research, yet many variables can potentially affect tissue stable isotope signatures. Controlled feeding studies across a range of species have consistently demonstrated impacts of caloric restriction on tissue stable isotope ratios, but most have focused on juvenile, fasting, and/or starving individuals, and most have utilized soft tissues despite the importance of bone for paleodietary analyses. The goal of this study was to determine whether temporally defined, moderate food restriction could affect stable carbon and/or nitrogen isotope ratios in adult mammalian bone - a tissue that arguably reflects long-term dietary signals. Adult rats fed a standard laboratory diet were restricted to 45% of ad libitum intakes for 3 or 6 months. Relevant anatomical and physiological parameters were measured to confirm that the restriction protocol resulted in significant nutritional stress and to provide independent data to facilitate interpretation of stable isotope ratios. Femoral bone δ(13)Ccollagen, δ(15)Ncollagen, and δ(13)Capatite values were determined by isotope ratio mass spectrometry. Calorie-restricted animals exhibited a small, yet significant enrichment in (15)Ncollagen compared with control animals, reflecting protein-calorie stress. While the δ(13)Ccollagen values did not differ, the δ(13)Capatite values revealed less enrichment in (13)C than in controls, reflecting catabolism of body fat. Independent anatomical and physiological data from these same individuals support these interpretations. Results indicate that moderate caloric restriction does not appreciably undermine broad interpretations of dietary signals in adult mammalian bone. Significant variability among individuals or groups, however, is best explained by marked differences in energy intake over variable timescales. An inverse relationship between the δ(13)Capatite and δ(15)Ncollagen

  10. Effects of long-term malnutrition and rehabilitation on the hippocampal formation of the adult rat. A morphometric study.

    PubMed Central

    Andrade, J P; Madeira, M D; Paula-Barbosa, M M

    1995-01-01

    We have previously shown that the numerical density of dentate granule and CA3 pyramidal cells of adult rats is reduced after lengthy periods of low-protein diet. In this study, the total number of these neurons was estimated, together with those for the hilar and CA1 pyramidal cells in order to obtain a complete and unbiased insight into the effects of malnutrition and rehabilitation from malnutrition on the structure of the hippocampal formation. Groups of 2-month-old rats were fed a low protein diet (8% casein) for 6, 12 and 18 months and compared with age-matched control and recovery rats. The recovery group was fed a low protein diet for 6 months and then switched to normal diet during the same period. Total numbers of neurons of each hippocampal region were calculated from their numerical density, estimated with the physical disector, and from the volume of the respective cell layers, after correction for the tissue shrinkage factor. The total number of granule, hilar, CA1 and CA3 pyramidal cells was reduced in all groups of malnourished rats including the recovery group. No differences were found between malnourished and recovery groups. These findings indicate that a prolonged low protein diet, started in adult life, leads to a deficit in neuronal numbers in the hippocampal formation, and that it may also disrupt the normal process of cell acquisition in the dentate gyrus. Moreover, our data support the view that the morphological alterations induced by a low protein intake are irreversible. Images Fig. 1 Fig. 2 Fig. 3 PMID:7592001

  11. Differential effects of stress on fear learning and activation of the amygdala in pre-adolescent and adult male rats.

    PubMed

    Barbayannis, Georgia; Franco, Daly; Wong, Solange; Galdamez, Josselyn; Romeo, Russell D; Bauer, Elizabeth P

    2017-09-30

    Adolescence is accompanied by the maturation of several stress-responsive areas of the brain including the amygdala, a key region for the acquisition and expression of conditioned fear. These changes may contribute to the development of stress-related disorders in adolescence, such as anxiety and depression, and increase the susceptibility to these psychopathologies later in life. Here, we assessed the effects of acute restraint stress on fear learning and amygdala activation in pre-adolescent and adult male rats. Pre-adolescents exposed to stress prior to fear conditioning showed greater resistance to the extinction of fear memories than adults. At the cellular level, the combination of stress and fear conditioning resulted in a greater number of FOS-positive cells in the basolateral nucleus of the amygdala (BLA) than fear conditioning alone, and this increase was greater in pre-adolescents than in adults. Despite age-dependent differences, we found no changes in glucocorticoid receptor (GR) levels in the amygdala of either pre-adolescent or adult males. Overall, our data indicate that stress prior to fear conditioning leads to extinction-resistant fear responses in pre-adolescent animals, and that the BLA may be one neural locus mediating these age-dependent effects of stress on fear learning. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Effect of neonatal handling on adult rat spatial learning and memory following acute stress.

    PubMed

    Stamatakis, A; Pondiki, S; Kitraki, E; Diamantopoulou, A; Panagiotaropoulos, T; Raftogianni, A; Stylianopoulou, F

    2008-03-01

    Brief neonatal handling permanently alters hypothalamic-pituitary-adrenal axis function resulting in increased ability to cope with stress. Since stress is known to affect cognitive abilities, in the present study we investigated the effect of brief (15 min) handling on learning and memory in the Morris water maze, following exposure to an acute restraint stress either before training or recall. Exposure of non-handled rats to the acute stress prior to training resulted in quicker learning of the task, than in the absence of the stressor. When acute stress preceded acquisition, male handled rats showed an overall better learning performance, and both sexes of handled animals were less impaired in the subsequent memory trial, compared to the respective non-handled. In addition, the number of neurons immunoreactive for GR was higher in all areas of Ammon's horn of the handled rats during the recall. In contrast, the number of neurons immunoreactive for MR was higher in the CA1 and CA2 areas of the non-handled males. When the acute restraint stress was applied prior to the memory test, neonatal handling was not effective in preventing mnemonic impairment, as all animal groups showed a similar deficit in recall. In this case, no difference between handled and non-handled rats was observed in the number of GR positive neurons in the CA2 and CA3 hippocampal areas during the memory test. These results indicate that early experience interacts with sex and acute stress exposure in adulthood to affect performance in the water maze. Hippocampal corticosterone receptors may play a role in determining the final outcome.

  13. Effects of chronic exercise and treatment with the antipsychotic drug olanzapine on hippocampal volume in adult female rats.

    PubMed

    Barr, A M; Wu, C H; Wong, C; Hercher, C; Töpfer, E; Boyda, H N; Procyshyn, R M; Honer, W G; Beasley, C L

    2013-01-01

    Numerous studies have reported that the hippocampus in schizophrenia patients is reduced in volume compared to the normal population. Antipsychotic medications have had mixed benefits in maintaining hippocampal volume or reversing volume loss. Recent evidence indicates that routine aerobic exercise represents a promising intervention for reversing hippocampal loss and cognitive deficits. In the present study, we measured the effects of chronic treatment with olanzapine and daily exercise on the hippocampal volumes of rats. Adult female rats were treated during the week with either olanzapine (10mg/kg) or vehicle for 9 consecutive weeks. Subgroups of animals were provided access to exercise running wheels for 1 or 3h per day during the same period, or were sedentary. Metabolic indices, including glucose tolerance, were measured on a weekly basis. At the conclusion of the study, brains were perfused and hippocampal sections were Nissl stained. Total hippocampal volume was measured using the Cavalieri estimator. Treatment with olanzapine caused a significant decrease in hippocampal volume in sedentary rats. However, exercise was able to reverse most of this volume loss. The hippocampal sub-regions of the dentate gyrus and CA1 were most strongly affected by olanzapine and exercise. Of interest, there was a strong and highly significant negative correlation between glucose intolerance and hippocampal volume, whereby greater glucose intolerance was associated with a smaller hippocampal volume. These findings indicate that exercise may have beneficial effects on the hippocampus when antipsychotic medication can contribute to changes in volume.

  14. Effect of gibberellic acid on the quality of sperm and in vitro fertilization outcome in adult male rats.

    PubMed

    Hosseinchi, Mohammadreza; Soltanalinejad, Farhad; Najafi, Gholamreza; Roshangar, Leila

    2013-01-01

    Gibberellic acid (GA3) is a group of plant hormones identified in various plants. The aim of this study was to determine the effects of GA3 on sperm parameters and in vitro fertilization (IVF). Fifty six adult male rats were divided into seven groups as, control, treatment and sham. Following 15, 30 and 45 days of GA3 and methanol alcohol (MA) administration, rats were euthanized and epididymis tail was transferred to human tubular fluid (HTF) medium containing 4 mg mL(-1) bovine serum albumin (BSA) .Total number of sperms, the percentage of live sperms, immature sperms and sperms with damaged chromatin and IVF were examined. The oocytes were obtained from immature rats after the injection of pregnant mare's serum (PMSG) and human chorionic gonadotropin (HCG) hormones. Human tubular fluid was used as the fertilization medium and zygotes transferred to fresh 1-cell rat embryos culture medium (mR1ECM) to reach the blastocyst stage. This study showed that GA3 could decrease the number of total sperms on days 30 and 45 in treated group comparison with the control and sham groups. Additionally, GA3 increased the immature sperms and sperms with damaged chromatin. The percentage of fertilization, two-cell embryos and blastocyst resulting from the treatment group on days 30 and 45 also decreased and showed significant differences with the control and sham groups (p < 0.05). The results obtained from this study indicated that the oral use of GA3 could reduce the fertility in rats by influencing the sperm number and the quality of sperm's chromatins.

  15. Effect of gibberellic acid on the quality of sperm and in vitro fertilization outcome in adult male rats

    PubMed Central

    Hosseinchi, Mohammadreza; Soltanalinejad, Farhad; Najafi, Gholamreza; Roshangar, Leila

    2013-01-01

    Gibberellic acid (GA3) is a group of plant hormones identified in various plants. The aim of this study was to determine the effects of GA3 on sperm parameters and in vitro fertilization (IVF). Fifty six adult male rats were divided into seven groups as, control, treatment and sham. Following 15, 30 and 45 days of GA3 and methanol alcohol (MA) administration, rats were euthanized and epididymis tail was transferred to human tubular fluid (HTF) medium containing 4 mg mL-1 bovine serum albumin (BSA) .Total number of sperms, the percentage of live sperms, immature sperms and sperms with damaged chromatin and IVF were examined. The oocytes were obtained from immature rats after the injection of pregnant mare's serum (PMSG) and human chorionic gonadotropin (HCG) hormones. Human tubular fluid was used as the fertilization medium and zygotes transferred to fresh 1-cell rat embryos culture medium (mR1ECM) to reach the blastocyst stage. This study showed that GA3 could decrease the number of total sperms on days 30 and 45 in treated group comparison with the control and sham groups. Additionally, GA3 increased the immature sperms and sperms with damaged chromatin. The percentage of fertilization, two-cell embryos and blastocyst resulting from the treatment group on days 30 and 45 also decreased and showed significant differences with the control and sham groups (p < 0.05). The results obtained from this study indicated that the oral use of GA3 could reduce the fertility in rats by influencing the sperm number and the quality of sperm’s chromatins. PMID:25568681

  16. Effects of neonatal and peripubertal ethanol treatment on various aspects of adult rat behavior and brain anatomy.

    PubMed

    Röskam, Stephan; Koch, Michael

    2009-05-01

    Exposure to ethanol during critical stages of brain development and maturation has adverse effects on behavioral and cognitive functions. So far, most animal models focused on the effects of either pre- or early postnatal ethanol treatment on behavior. We here used a multiple crossover design to investigate the effects of neonatal (postnatal day 7) ethanol treatment (2.5 g/kg b.i.d., dissolved in saline), subchronic peripubertal (postnatal days 40-65) ethanol treatment (1.0 g/kg, dissolved in saline) and the combination of both on the performance of adult Wistar rats in a variety of behavioral tasks. We also assessed anatomical changes in limbic and cortical brain areas. No effects of either single or combined neonatal and pubertal ethanol treatment was found on prepulse inhibition of startle (PPI, a measure of sensorimotor gating), or on the acoustic startle response in the absence of prepulses. Peripubertal ethanol treatment reduced the explorative behavior in the open field. The breakpoint in a progressive ratio operant response task was increased in those rats that had received both neonatal and pubertal ethanol treatment, while the preference for palatable food used as reinforcer in this task was not affected. No treatment effects were found on object recognition memory. No treatment effects on anxiety-related behavior in the elevated plus maze were found, however, the anxiolytic effect of the prototypical benzodiazepine diazepam was enhanced in rats that had received peripubertal ethanol treatment. Additive effects of neonatal and pubertal ethanol treatments were found on behaviors related to spontaneous locomotor activity. Combined neonatal and pubertal ethanol treatment lead to a reduction of myelin sheaths in the prefrontal cortex, and the neonatal ethanol treatment lead to a reduced number of parvalbumine-immunoreactive cells in the dorsal hippocampus. These findings suggest that neonatal ethanol exposure increases the risk of some but not all adverse

  17. Effect of chromium supplementation on the diabetes induced-oxidative stress in liver and brain of adult rats.

    PubMed

    Refaie, Fawzia M; Esmat, Amr Y; Mohamed, Aly F; Aboul Nour, Wael H

    2009-12-01

    This study was designed to investigate the susceptibility of liver and brain tissues, as insulinin-dependent tissues, of normal adult male rats to the oxidative challenge of subchronic supplementation with chromium picolinate (CrPic) at low (human equivalent) and high doses (2.90 and 13.20 μg Cr kg(-1) day(-1), respectively). Also, the modulative effect of CrPic administration on the enhanced oxidative stress in the liver and brain tissues of alloxan-diabetic rats was studied. Fasting serum glucose level was not modified in normal rats but significantly reduced in diabetic rats that had received CrPic supplement. A mild oxidative stress was observed in the liver and brain of CrPic-supplemented normal rats confirmed by the dose-dependent reductions in the levels of hepatic and cerebral free fatty acids, superoxide dismutase and glutathione peroxidase activities, and in contrast increased tissue malondialdehyde concentration. On the other hand, hepatic and cerebral catalase activity was reduced in the high dose group only. CrPic supplementation did not act as a peroxisome proliferator confirmed by the significant reductions in liver and brain peroxisomal palmitoyl CoA oxidase activity. The non significant alterations in liver protein/DNA and RNA/DNA ratios indicate that CrPic did not affect protein synthesis per cell, and that mild elevations in hepatic total protein and RNA concentrations might be due to block or decrease in the export rate of synthesized proteins from the liver to the plasma. In diabetic rats, elevated levels of hepatic and cerebral free fatty acids and malondialdehyde, and in contrast the overwhelmed antioxidant enzymes, were significantly modulated in the low dose group and near-normalized in the high dose group. The significant increases observed in liver total protein and RNA concentrations, as well as protein/DNA and RNA/ DNA ratios in diabetic rats supplemented with the high dose of Cr, compared to untreated diabetics, may be related to the

  18. Adult exercise effects on oxidative stress and reproductive programming in male offspring of obese rats.

    PubMed

    Santos, Mery; Rodríguez-González, Guadalupe L; Ibáñez, Carlos; Vega, Claudia C; Nathanielsz, Peter W; Zambrano, Elena

    2015-02-01

    Exercise improves health but few data are available regarding benefits of exercise in offspring exposed to developmental programming. There is currently a worldwide epidemic of obesity. Obesity in pregnant women predisposes offspring to obesity. Maternal obesity has well documented effects on offspring reproduction. Few studies address ability of offspring exercise to reduce adverse outcomes. We observed increased oxidative stress and impaired sperm function in rat offspring of obese mothers. We hypothesized that regular offspring exercise reverses adverse effects of maternal obesity on offspring sperm quality and fertility. Female Wistar rats ate chow (C) or high-energy, obesogenic diet (MO) from weaning through lactation, bred at postnatal day (PND) 120, and ate their pregnancy diet until weaning. All offspring ate C diet from weaning. Five male offspring (different litters) ran on a wheel for 15 min, 5 times/week from PND 330 to 450 and were euthanized at PND 450. Average distance run per session was lower in MO offspring who had higher body weight, adiposity index, and gonadal fat and showed increases in testicular oxidative stress biomarkers. Sperm from MO offspring had reduced antioxidant enzyme activity, lower sperm quality, and fertility. Exercise in MO offspring decreased testicular oxidative stress, increased sperm antioxidant activity and sperm quality, and improved fertility. Exercise intervention has beneficial effects on adiposity index, gonadal fat, oxidative stress markers, sperm quality, and fertility. Thus regular physical exercise in male MO offspring recuperates key male reproductive functions even at advanced age: it's never too late. Copyright © 2015 the American Physiological Society.

  19. The beneficial effects of olibanum on memory deficit induced by hypothyroidism in adult rats tested in Morris water maze.

    PubMed

    Hosseini, Mahmoud; Hadjzadeh, Mosa Al-Reza; Derakhshan, Mohammad; Havakhah, Shahrzad; Rassouli, Fatemeh Behnam; Rakhshandeh, Hassan; Saffarzadeh, Fatema

    2010-03-01

    Functional consequences of hypothyroidism include impaired learning and memory and inability to produce long-term potentiation (LTP) in hippocampus. Olibanum has been used for variety of therapeutic purposes. In traditional medicine, oilbanum is used to enhance learning and memory. In the present study the effect of olibanum on memory deficit in hypothyroid rats was investigated. Male wistar rats were divided into four groups and treated for 180 days. Group 1 received tap drinking water while in group 2, 0.03% methimazol was added to drinking water. Group 3 and 4 were treated with 0.03% methimazole as well as 100 and 500 mg/kg olibanum respectively. The animals were tested in Morris water maze. The swimming speed was significantly lower and the distance and time latency were higher in group 2 compared with group 1. In groups 3 and 4 the swimming speed was significantly higher while, the length of the swim path and time latency were significantly lower in comparison with group 2. It is concluded that methimazole-induced hypothyroidism impairs learning and memory in adult rats which could be prevented by using olibanum.

  20. The effects of cyclosporin-A on functional outcome and axonal regrowth following spinal cord injury in adult rats.

    PubMed

    Roozbehi, Amrollah; Joghataie, Mohammad Taghi; Mehdizadeh, Mehdi; Mirzaei, Ali; Delaviz, Hamdollah

    2012-01-01

    It has been shown that the immunophilin ligands have the special advantage in spinal cord repair. In this study, the effects of cyclosporine A (CsA) on functional recovery and histological outcome were evaluated following spinal cord injury in rats. After spinal cord hemisection in thirty six adult female Sprague-Dawley rats (200- 250 g), treatment groups received CsA (2.5 mg/kg i.p.) at 15min and 24h after lesion (CsA 15min group and CsA 24h group) daily, for 8 weeks. Control and sham groups received normal saline and in sham operated animals the spinal cord was exposed in the same manner as treatment groups, but was not hemisected. Hindlimb motor function was assessed in 1, 3, 5 and 7 weeks after lesion, using locomotive rating scale developed by Basso, Bresnahan and Beattie (BBB). Motor neurons were counted within the lamina IX of ventral horn and lesion size was measured in 5 mm of spinal lumbar segment with the epicenter of the lesion site. The mean number of motor neurons and the mean BBB scale in 3, 5 and 7 weeks in CsA 15min groups significantly increased compared to the control group. Although, the lesion size reduced in rats with CsA treatment compared to the control group, no significant difference was observed. Thus, it can be concluded that CsA can improve locomotor function and histological outcome in the partial spinal cord injury.

  1. Effects of enriched housing on functional recovery after spinal cord contusive injury in the adult rat.

    PubMed

    Lankhorst, A J; ter Laak, M P; van Laar, T J; van Meeteren, N L; de Groot, J C; Schrama, L H; Hamers, F P; Gispen, W H

    2001-02-01

    To date, most research performed in the area of spinal cord injury focuses on treatments designed to either prevent spreading lesion (secondary injury) or to enhance outgrowth of long descending and ascending fiber tracts around or through the lesion. In the last decade, however, several authors have shown that it is possible to enhance locomotor function after spinal cord injury in both animals and patients using specific training paradigms. As a first step towards combining such training paradigms with pharmacotherapy, we evaluated recovery of function in adult rats sustaining a spinal cord contusion injury (MASCIS device, 12.5 mm at T8), either housed in an enriched environment or in standard cages (n = 15 in both groups). The animals in the enriched environment were stimulated to increase their locomotor activity by placing water and food on opposite sides of the cage. As extra stimuli, a running wheel and several other objects were added to the cage. We show that exposure to the enriched environment improves gross and fine locomotor recovery as measured by the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, the BBB subscale, the Gridwalk, and the Thoracolumbar height test. However, no group differences were found on our electrophysiological parameters nor on the amount of spared white matter. These data justify further studies on enriched housing and more controlled exercise training, with their use as potential additive to pharmacological intervention.

  2. Chronic intermittent ethanol exposure in adolescent and adult male rats: Effects on tolerance, social behavior and ethanol intake

    PubMed Central

    Broadwater, Margaret; Varlinskaya, Elena I.; Spear, Linda P.

    2010-01-01

    Background Given the prevalence of alcohol use in adolescence, it is important to understand the consequences of chronic ethanol exposure during this critical period in development. The purpose of the present study was to assess possible age-related differences in susceptibility to tolerance development to ethanol-induced sedation and withdrawal-related anxiety, as well as voluntary ethanol intake after chronic exposure to relatively high doses of ethanol during adolescence or adulthood. Methods Adolescent and adult male Sprague-Dawley rats were assigned to one of five 10 day exposure conditions: chronic ethanol (4 g/kg every 48 hours), chronic saline (equivalent volume every 24 hours), chronic saline/acutely challenged with ethanol (4 g/kg on day 10), non-manipulated/acutely challenged with ethanol (4 g/kg on day 10) or non-manipulated. For assessment of tolerance development, loss of righting reflex was tested on the first and last ethanol exposure days in the chronic ethanol group, with both saline and non-manipulated animals likewise challenged on the last exposure day. Withdrawal-induced anxiety was indexed in a social interaction test 24 hrs after the last ethanol exposure, with ethanol-naïve chronic saline and non-manipulated animals serving as controls. Voluntary intake was assessed 48 hours after the chronic exposure period in chronic ethanol, chronic saline and non-manipulated animals using an 8 day 2 bottle choice, limited access ethanol intake procedure. Results Adolescents were less sensitive to the sedative effects of ethanol than adults. Adults, but not adolescents, developed chronic tolerance to the sedative effects of ethanol, tolerance that appeared to be metabolic in nature. Social deficits were observed after chronic ethanol in both adolescents and adults. Adolescents drank significantly more ethanol than adults on a g/kg basis, with intake uninfluenced by prior ethanol exposure at both ages. Conclusion Adolescents and adults may differ in

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

    PubMed

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

    2013-03-01

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

  4. Mutagenic effect of Bisphenol A on adult rat male germ cells and their fertility.

    PubMed

    Tiwari, Dinesh; Vanage, Geeta

    2013-09-01

    The present study investigates the effects of Bisphenol A on the induction of dominant lethal mutation and male reproductive functions. The male rats were gavaged with BPA (10 μg, and 5.0 mg/kg/bw) over a period of six days and control group with vehicle. Each male was cohabited with untreated females sequentially over the period of eight weeks. The mated females were sacrificed on 15th day of gestation. The results revealed a significant increase in dominant lethal mutation rate during fourth and sixth week of mating intervals at 5.0mg/kgbw dose of BPA. These findings demonstrate that mid-spermatids and spermatocytes are more sensitive to BPA exposure. The male rats sacrificed at the end of mating study showed an increase in the sperm DNA damage, and decrease in motility at higher dose. However, significant reductions in sperm production effects were observed at both lower and higher doses of BPA. These preliminary results indicate that BPA may be a weak male germ cell mutagen.

  5. Effect of continuous gamma-radiation on the stem and differentiating spermatogonia of the adult rat.

    PubMed

    Erickson, B H

    1978-10-01

    Sprague-Dawley rats were irradiated continuously (60Co, gamma) at a dose-rate of either 1 (0.0007 rad/min), 3 or 6 rad/23-h day for monthly intervals of 1 to 6. At one month after irradiation, counts of differentiating spermatogonia (A1 and A4) were reduced to a level that remained essentially unchanged during the succeeding 5 months of irradiation. The magnitude of the irradiation effect was greatest at stage 1 of the spermatogenic cycle where numbers of differentiating spermatogonia were reduced to 50% of control by 1 rad/day and to 30 and 20% of control by 3 and 6 rad/day, respectively. Number of stem spermatogonia was not significantly affected by 1 rad/day (P greater than 0.10). At 3 and 6 rad, however, number of stem cells declined from 80% of control at 1 month to 60 and 40% of control at 6 months, respectively. At a dose-rate of 1 rad/day there was neither a reduction in number of A1 spermatogonia per clone nor significant evidence of necrosis among either stem or differentiating spermatogonia; therefore, a reduction of stem-cell mitotic activity appears to be the principal effect of continuous low-level irradiation on spermatogenesis in the rat.

  6. Gender difference in the effect of intrauterine malnutrition on the central anorexigenic action of insulin in adult rats.

    PubMed

    Sardinha, Fátima L C; Telles, Mônica M; Albuquerque, Kelse T; Oyama, Lila M; Guimarães, Paulo A M P; Santos, Oscar F P; Ribeiro, Eliane B

    2006-01-01

    We evaluated whether insulin hypophagia and hypothalamic signaling are affected in adult rats exposed to intrauterine undernutrition. Pregnant rats ate ad libitum throughout pregnancy and lactation (control, C) or 50% of control intake in the first 2 wk of pregnancy (restricted, R). Four-month-old C and R progeny received insulin or vehicle intracerebroventricular injections for evaluation of 24-h food intake, hypothalamic insulin receptor (IR), and IR substrate-1 (IRS-1) protein content and tyrosine phosphorylation, pp185 phosphorylation, and IRS-1 association with phosphatidylinositol 3-kinase (PI3-K). With respect to males, R males had normal body composition and insulin-induced hypophagia. IR protein levels were lower but IR phosphorylation was higher in R than in C males. IRS-1 levels and phosphorylation were similar between C and R males, insulin stimulated an IRS-1/PI3-K association in C but not in R males, and pp185 phosphorylation was higher in R than in C males. For females, body fat and serum leptin were elevated in R females. Insulin inhibited food intake in C but not in R females. Insulin-induced IR phosphorylation and protein levels of IR and IRS-1 were higher in R than in C females. However, IRS-1 and pp185 phosphorylation and IRS-1/PI3-K association were significantly stimulated by insulin in C but not in R females. Female adult rats exposed to intrauterine undernutrition had increased adiposity, marked impairment of hypothalamic insulin signaling, and loss of insulin-induced hypophagia. These disturbances were less severe or even absent in male progeny. The findings show that female progeny are more susceptible than their male siblings to the effects of maternal malnutrition.

  7. Effect of High Fructose Corn Syrup (HFCS) Intake on the Female Reproductive Organs and Lipid Accumulation in Adult Rats

    PubMed Central

    Ko, Eun-Ah; Kim, Hye-Ri; Kim, Yong-Bin; Kim, Hee-Su; Lee, Sung-Ho

    2017-01-01

    ABSTRACT High-fructose corn syrup (HFCS) is widely used as sweetener, and its overconsumption is become a major health problem. In the present study, we used adult female rats and applied a 28 days HFCS feeding model to monitor the estrous cycle and changes in tissue weights and histology. Adult female rats were divided into three groups. Animals were fed with ad libitum normal chow and (1) 24 hours tap water (Control group), (2) 12 hours HFCS access during dark period and 12 hours tap water (12H group), and (3) 24 hours HFCS only access (24H group). Total exposure period was 28 days. There is no significant change in body weight between control and HFCS-fed animals. Both absolute and relative weights of ovary in 24H animals were significantly heavier than those in control or 12H animals. The absolute and relative weights of the kidney and liver in 24H groups were significantly heavier than those in control or 12H animals. The estrous cycles of the 24H animals were significantly longer. Histological analyses revealed that 24H ovaries were relatively bigger and possessed more corpus lutea than control ovaries. Uterine sections of 12H and 24H animals showed a well-developed stratum vasculare between inner and outer myometrial layers. The number of endometrial glands were decreased in 12H uteri, and recovered in 24H uteri compared to control. Numbers of convoluted tubule in distal region increased in 12H and 24H kidney samples. Liver specimens of 12H and 24H showed the increased number of fat containing vacuoles. In conclusion, our study demonstrated that HFCS treatment for 28 days could induce (1) changes in length of estrous cycle with extended estrous and diestrous stages, (2) altered ovarian and uterine histology, and (3) liver and renal lipid accumulation. These findings reveal the adverse effects of HFCS drinking on the reproductive function and lipid metabolism of female rats. PMID:28785736

  8. Effect of High Fructose Corn Syrup (HFCS) Intake on the Female Reproductive Organs and Lipid Accumulation in Adult Rats.

    PubMed

    Ko, Eun-Ah; Kim, Hye-Ri; Kim, Yong-Bin; Kim, Hee-Su; Lee, Sung-Ho

    2017-06-01

    High-fructose corn syrup (HFCS) is widely used as sweetener, and its overconsumption is become a major health problem. In the present study, we used adult female rats and applied a 28 days HFCS feeding model to monitor the estrous cycle and changes in tissue weights and histology. Adult female rats were divided into three groups. Animals were fed with ad libitum normal chow and (1) 24 hours tap water (Control group), (2) 12 hours HFCS access during dark period and 12 hours tap water (12H group), and (3) 24 hours HFCS only access (24H group). Total exposure period was 28 days. There is no significant change in body weight between control and HFCS-fed animals. Both absolute and relative weights of ovary in 24H animals were significantly heavier than those in control or 12H animals. The absolute and relative weights of the kidney and liver in 24H groups were significantly heavier than those in control or 12H animals. The estrous cycles of the 24H animals were significantly longer. Histological analyses revealed that 24H ovaries were relatively bigger and possessed more corpus lutea than control ovaries. Uterine sections of 12H and 24H animals showed a well-developed stratum vasculare between inner and outer myometrial layers. The number of endometrial glands were decreased in 12H uteri, and recovered in 24H uteri compared to control. Numbers of convoluted tubule in distal region increased in 12H and 24H kidney samples. Liver specimens of 12H and 24H showed the increased number of fat containing vacuoles. In conclusion, our study demonstrated that HFCS treatment for 28 days could induce (1) changes in length of estrous cycle with extended estrous and diestrous stages, (2) altered ovarian and uterine histology, and (3) liver and renal lipid accumulation. These findings reveal the adverse effects of HFCS drinking on the reproductive function and lipid metabolism of female rats.

  9. Alcohol Exposure During Late Adolescence Increases Drinking in Adult Wistar Rats, an Effect that is not Reduced by Finasteride

    PubMed Central

    Milivojevic, Verica; Covault, Jonathan

    2013-01-01

    Aims: We tested whether an exposure to alcohol in late adolescence, an age of rapid increase in neuroactive steroid precursors, would increase voluntary alcohol consumption in adult rats and whether this effect would be modulated by finasteride, an inhibitor of neuroactive steroid synthesis. Methods: In Experiment 1, we exposed male Wistar rats to 8% alcohol during the dark cycle for 1 week during late adolescence [postnatal days (PNDs) 51–58], and then measured voluntary alcohol consumption 1 month later in adulthood (PNDs 91–104). In Experiment 2, finasteride was administered during the forced alcohol exposure in late adolescence and, in Experiment 3, during voluntary alcohol consumption in adulthood. Plasma was collected at the end of each finasteride treatment to confirm the reduction of plasma neuroactive steroid levels. Results: We found that a daily 12-h exposure to alcohol for 7 days in late adolescence significantly increased voluntary alcohol consumption (4-fold) a month later during adulthood. Finasteride administration in late adolescence increased group alcohol intake in late adolescence but did not block the effect of adolescent alcohol exposure on increasing alcohol preference in adulthood. There was no effect of finasteride treatment in adulthood on alcohol preference. Conclusions: A daily 12-h exposure to alcohol for 7 days in late adolescence was sufficient to induce chronically increased alcohol preference in adulthood, indicating that this age may be sensitive to the effects of alcohol. PMID:22997410

  10. Episodic ozone exposure in adult and senescent Brown Norway rats: acute and delayed effect on heart rate, core temperature and motor activity.

    PubMed

    Gordon, C J; Johnstone, A F; Aydin, C; Phillips, P M; MacPhail, R C; Kodavanti, U P; Ledbetter, A D; Jarema, K A

    2014-06-01

    Setting exposure standards for environmental pollutants may consider the aged as a susceptible population but the few published studies assessing susceptibility of the aged to air pollutants are inconsistent. Episodic ozone (O₃) is more reflective of potential exposures occurring in human populations and could be more harmful to the aged. This study used radiotelemetry to monitor heart rate (HR), core temperature (T(c)) and motor activity (MA) in adult (9-12 months) and senescent (20-24 months) male, Brown Norway rats exposed to episodic O₃ (6 h/day of 1 ppm O₃ for 2 consecutive days/week for 13 weeks). Acute O₃ initially led to marked drops in HR and T(c). As exposures progressed each week, there was diminution in the hypothermic and bradycardic effects of O₃. Senescent rats were less affected than adults. Acute responses were exacerbated on the second day of O₃ exposure with adults exhibiting greater sensitivity. During recovery following 2 d of O₃, adult and senescent rats exhibited an elevated T(c) and HR during the day but not at night, an effect that persisted for at least 48 h after O₃ exposure. MA was elevated in adults but not senescent rats during recovery from O₃. Overall, acute effects of O₃, including reductions in HR and T(c), were attenuated in senescent rats. Autonomic responses during recovery, included an elevation in T(c) with a pattern akin to that of a fever and rise in HR that were independent of age. An attenuated inflammatory response to O₃ in senescent rats may explain the relatively heightened physiological response to O₃ in younger rats.

  11. Effects of ceftriaxone on the acquisition and maintenance of ethanol drinking in peri-adolescent and adult female alcohol-preferring (P) rats

    PubMed Central

    Sari, Youssef; Franklin, Kelle M.; Alazizi, Adnan; Rao, P.S.S.; Bell, Richard L.

    2013-01-01

    Increased glutamatergic neurotransmission appears to mediate the reinforcing properties of drugs of abuse, including ethanol (EtOH). We recently reported that the administration of ceftriaxone (CEF), a β-lactam antibiotic known to upregulate glutamate transporter 1 (GLT1) levels/activity, decreased the maintenance of EtOH intake in adult male alcohol-preferring (P) rats. In the present study, we tested whether CEF administration would reduce the acquisition and maintenance of EtOH drinking in adolescent and adult female P rats. The rats were treated with saline or 200 mg/kg ceftriaxone for 7 days (starting at 35 or 75 days old, respectively) followed by the EtOH acquisition test. Five weeks later the effects of CEF were examined regarding the maintenance of EtOH intake. For the maintenance test, half of the animals that received CEF during acquisition received CEF for 7 days and the other half received saline for 7 days. Saline-treated acquisition animals were treated similarly. The results indicated that pretreatment with ceftriaxone reduced the maintenance of EtOH intake in both animals that started as adolescents and those that started as adults. However, the beneficial effect of CEF was more pronounced in rats pretreated with CEF as adults compared with rats pretreated as adolescents. Reductions in EtOH intake by ceftriaxone were paralleled by an upregulation of GLT1 protein levels in both the nucleus accumbens (µ25% in rats starting at both ages) and prefrontal cortex (µ50% in rats starting as peri-adolescents and µ65% in those starting as adults). These findings provide further support for GLT1-associated mechanisms in high alcohol consuming behavior, and hold promise for the development of effective treatments targeting alcohol abuse and dependence. PMID:23537837

  12. Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.

    PubMed

    Gonçalves, Cinara L; Rezin, Gislaine T; Ferreira, Gabriela K; Jeremias, Isabela C; Cardoso, Mariane R; Valvassori, Samira S; Munhoz, Bruna J P; Borges, Gabriela D; Bristot, Bruno N; Leffa, Daniela D; Andrade, Vanessa M; Quevedo, João; Streck, Emilio L

    2013-08-01

    Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage.

  13. Effects of ciprofloxacin and zinc chloride in adult albino rat and pre-natal conceptus.

    PubMed

    Channa, Muhammad Aslam; Ashfaq, Muhammad; Jokhio, Abdul Lateef; Khan, Muhammad Zaheer; Sahito, Mir Muhammad

    2012-01-01

    Administration of quinolone therapy is controversial during growing age as stated by earlier authors. The flouroquinolones are currently not indicated for young children because of arthropathy and adverse effect as new born shown by studies. However the effects of ciprofloxacin and ZnCl2 on prenatal conceptus have remained undocumented. The present study was designed to compare the effects on conceptus after maternal ingestion of ciprofloxacin and ZnCl2 using Wastar albino rats. Ciprofloxacin and ZnCl2 was administrated to pregnant female albino rats. Ciprofloxacin with a dose of 20 mg/Kg bodyweight and ZnCl2 120 microg/100 gm bodyweight two times therapeutic dose for 10 days (from day 8-18 of pregnancy). Each animal was weighted on day 1, day 8 and day 18 of pregnancy. Abortion resulted on day 18th of pregnancy. Each group of pregnant animals were sacrificed on day 18 of gestation by over dose of either anaesthesia, abdomen opened, uterus and both cornua containing conceptus identified, removed, there weight recorded, crown rump length was measured and was compared with similar value of control animals. The results were statistically analysed to find out the significance. The ciprofloxacin induces a mordanting effect as obviated by increased basophilia. Our study reveals that ciprofloxacin administered in maternal, decreased maternal body weight to 38.4 +/- 0.9 gm. However simultaneous ZnCl2 maintained the body weight to 41.4 +/- 0.7 gm, while ZnCl2 increased the body weight to 46.5 +/- 2.25 gm. The body weight and Crown Rump length (CR Length) in conceptus decreased by 4.52 +/- 0.10 gm and 3.06 +/- 0.09 Cm respectively. That ciprofloxacin and ZnCl2 administration maintained the body weight and CR length by 5.46 +/- 0.09 gm and 3.79 +/- 0.13 Cm respectively. That ZnCl2 administration increased the body weight and CR length by 6.71 +/- 0.05 gm and 4.15 +/- 0.08 Cm respectively. Prenatal administration of Ciprofloxacin caused reduction in growth rate and CR length

  14. Effect of chromium on vertebrae, femur and calvaria of adult male rats.

    PubMed

    Sankaramanivel, S; Jeyapriya, R; Hemalatha, D; Djody, S; Arunakaran, J; Srinivasan, N

    2006-06-01

    Alloys of chromium have a long history of success in the surgical treatment of many orthopaedic defects. Nonetheless, prostheses loosening are commonly found around arthoplasties due to corrosion of metals. On this basis, it is hypothesized that chromium accumulation interferes with remodeling of bone. The present study aims to analyse the toxic effects of chromium on bone phosphatases in various regions of the bone in rats. Rats were treated with chromium intraperitoneally (0.5 mg/kg) in the form of potassium dichromate for 5 days. The accumulation of chromium is approximately 5.2-fold in the vertebrae, 8.9-fold in the femur and 8.7-fold in the calvaria, when compared to control. Chromium administration significantly reduced the activity of enzymes, eg, alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP). The study revealed a significant increase in the concentration of calcium, altered bone formation rate and bone morphology in the femur, vertebrae and calvaria. The interesting findings of the current study suggest altered bone turnover.

  15. Effects of selenium on chromium (VI)-induced hepatotoxicity in adult rats.

    PubMed

    Soudani, Nejla; Ben Amara, Ibtissem; Sefi, Mediha; Boudawara, Tahia; Zeghal, Najiba

    2011-09-01

    Chromium, a major environmental pollutant, is known for its wide toxic manifestations. The present experiment pertains to the protective role of selenium (Se) against K(2)Cr(2)O(7)-induced hepatotoxicity. Female Wistar rats were divided into four groups of six each: group I served as controls which received standard diet; group II received in drinking water K(2)Cr(2)O(7) alone (700 ppm); group III received both K(2)Cr(2)O(7) and Se (0.5 Na(2)SeO(3) mg/kg of diet); group IV received Se (0.5 mg/kg of diet) for 3 weeks. Exposure of rats to chromium promoted oxidative stress with an increase in malondialdehyde (MDA) and a decrease in glutathione (GSH) levels. A decrease in glutathione peroxidase (GPx) and an increase in superoxide dismutase (SOD) and catalase (CAT) activities were observed. Se supplementation to the diet of group III improved all the parameters cited above. Yet, plasma transaminases (AST and ALT), lactate dehydrogenase (LDH) activities, cholesterol, triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) levels increased, while high density lipoprotein-cholesterol (HDL-C) decreased. Co-administration of Se to the diet of group III restored hepatic markers to near-normal values. The biochemical results confirmed the histopathological findings. Therefore, our investigation revealed that Se was effective in preventing K(2)Cr(2)O(7)-induced hepatotoxicity. Copyright © 2010 Elsevier GmbH. All rights reserved.

  16. Effects of Rapid or Slow Body Mass Reduction on Body Composition in Adult Rats

    PubMed Central

    Tai, Shinji; Tsurumi, Yasukimi; Yokota, Yukari; Masuhara, Mitsuhiko; Okamura, Koji

    2009-01-01

    Whether the speed of body mass (BM) reduction influences the body composition is uncertain. To investigate the effects of rapid vs slow body mass reduction on body composition, rats were divided into three groups; fed ad libitum for 16-day (Control, C); received restricted food intake during 16-day to decrease BM slowly (Slow, S); or fed ad libitum for 13-days and fasted for the last 3 days to rapidly reach a BM comparable to that of S (Rapid, R). Drinking water was restricted for R on day 16 to rapidly decrease their BM. All rats trained during the study. Final BM and adipose tissues mass were similar for R and S, and both were lesser than C. The skeletal muscle mass did not decrease in R and S. The liver mass was lower in R and S than C, and the decrease tended to be greater in R than S. Both the stomach and small intestine masses were significantly lower in R than C, but did not differ between S and C. In conclusion, differences of the speed of BM reduction affect the splanchnic tissues, and the decrease in splanchnic tissue mass was greater with rapid than slow BM reduction. PMID:19794927

  17. Hepatoprotective effect of Arctium lappa root extract on cadmium toxicity in adult Wistar rats.

    PubMed

    de Souza Predes, Fabricia; da Silva Diamante, Maria Aparecida; Foglio, Mary Ann; Camargo, Camila de Andrade; Camargo, Camila Almeida; Aoyama, Hiroshi; Miranda, Silvio Cesar; Cruz, Bread; Gomes Marcondes, Maria Cristina Cintra; Dolder, Heidi

    2014-08-01

    This study was performed to determine the effects of Arctium lappa (Al) to protect against cadmium damage in the rat liver. Male rats received a single i.p. dose of CdCl2 (1.2 mg/kg body weight (BW)) with or without Al extract administered daily by gavage (300 mg/kg BW) for 7 or 56 days. After 7 days, Al caused plasma transaminase activity to diminish in groups Al (glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT)) and CdAl (GPT). After 56 days, GOT and GPT plasma activities were reduced in the Cd group. No alteration in plasma levels of creatinine, total bilirubin, and total protein were observed. GOT liver activity increased in the Cd group. No alteration was observed in superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and malondialdehyde (MDA) dosage. In the Cd group, hepatocyte proportion decreased and sinusoid capillary proportion increased. In the Al and CdAl groups, the nuclear proportion increased and the cytoplasmic proportion decreased. The hepatocyte nucleus density reduced in Cd and increased in the Al group. After 56 days, there was no alteration in the Cd group. In Al and CdAl groups, the nuclear proportion increased without cytoplasmic proportion variation, but the sinusoid capillary proportion was reduced. The hepatocyte nucleus density decreased in the Cd group and increased in the Al and CdAl groups. In conclusion, the liver function indicators showed that A. lappa protected the liver against cadmium toxicity damage.

  18. The effects of neurochemical lesioning of dopaminergic terminals in early ontogenesis on behavior in adult rats.

    PubMed

    Shabanov, P D; Lebedev, A A; Meshcherov, Sh K; Strel'tsov, V F

    2005-06-01

    6-Hydroxydopamine, which induces selective degeneration of the dopaminergic system of the brain, was given intraamniotically to rats on days 13 and 17 of intrauterine development at a dose of 75 microg/fetus. Similar experiments were performed with 6-hydroxydopamine on days 4 and 10 of neonatal life. Rats were subsequently reared and motor and emotional (dopamine-dependent) types of behavior were studied in adulthood, addressing behavior in the open field test, rotatory behavior, anxiety in an elevated cross maze, a place-preference conditioned response, acquisition of the ability to differentiate new and old arms in a Y maze, aggressivity in the "foreigner-resident" test, and self-stimulation in a Skinner box. Prenatal exposure, to a lesser extent than postnatal exposure, initiated rotatory and stereotypical behavior, decreased the level of anxiety (fear) in the elevated maze, and reinforced the effects of phenamine in the conditioned place-preference test, impaired the differentiation of old and new Y-maze arms, impaired aggressivity in the "foreigner-resident" test, and impaired self-stimulation of the lateral hypothalamus. It is concluded that the early postnatal period of development is more sensitive to the action of this neurotoxin than the prenatal period. This is associated with the critical periods of the formation of the dopaminergic system during ontogenesis, which depend on synaptogenesis.

  19. Projection neurons in the cortex and hippocampus: differential effects of chronic khat and ethanol exposure in adult male rats

    PubMed Central

    Alele, Paul E; Matovu, Daniel; Imanirampa, Lawrence; Ajayi, Abayomi M; Kasule, Gyaviira T

    2016-01-01

    Background Recent evidence suggests that many individuals who chew khat recreationally also drink ethanol to offset the stimulating effect of khat. The objective of this study was to describe the separate and interactive effects of chronic ethanol and khat exposure on key projection neurons in the cortex and hippocampus of young adult male rats. Methods Young adult male Sprague Dawley rats were divided into six treatment groups: 2 g/kg khat, 4 g/kg khat, 4 g/kg ethanol, combined khat and ethanol (4 g/kg each), a normal saline control, and an untreated group. Treatments were administered orally for 28 continuous days; brains were then harvested, sectioned, and routine hematoxylin–eosin staining was done. Following photomicrography, ImageJ® software captured data regarding neuron number and size. Results No differences occurred in counts of both granular and pyramidal projection neurons in the motor cortex and all four subfields of the hippocampal formation. Khat dose-dependently increased pyramidal neuron size in the motor cortex and the CA3 region, but had different effects on granular neuron size in the dentate gyrus and the motor cortex. Mean pyramidal neuron size for the ethanol-only treatment was larger than that for the 2 g/kg khat group, and the saline control group, in CA3 and in the motor cortex. Concomitant khat and ethanol increased granular neuron size in the motor cortex, compared to the 2 g/kg khat group, the 4 g/kg khat group, and the 4 g/kg ethanol group. In the CA3 region, the 4 g/kg ethanol group showed a larger mean pyramidal neuron size than the combined khat and ethanol group. Conclusion These results suggest that concomitant khat and ethanol exposure changes granular and pyramidal projection neuron sizes differentially in the motor cortex and hippocampus, compared to the effects of chronic exposure to these two drugs separately. PMID:27785113

  20. The effect of red wine consumption on hormonal reproductive parameters and total antioxidant status in young adult male rats.

    PubMed

    Oczkowski, Michał; Średnicka-Tober, Dominika; Stachoń, Małgorzata; Kołota, Aleksandra; Wolińska-Witort, Ewa; Malik, Agnieszka; Hallmann, Ewelina; Rusaczonek, Anna; Gromadzka-Ostrowska, Joanna

    2014-09-01

    Very little is known about the effects of red wine consumption on male reproductive functions. Here we report the effect of regular drinking of different types of red wine on hormonal reproductive parameters and total antioxidant status in young adult male rats. Dry red wine (D-RW) exerted higher antioxidant activity and was characterized by higher concentration of phenolic compounds compared to semi-dry (SD-RW), sweet (S-RW) and semi-sweet (SS-RW) wines. No differences in total antioxidant status of rat plasma after six weeks of drinking of the wines were detected. Increased plasma follicle-stimulating hormone levels in S-RW versus control and D-RW (5.26 vs. 3.06 and 3.21 ng mL(-1)) groups were found. The plasma testosterone concentration was lower in D-RW compared to control, SD-RW, S-RW and SS-RW groups (0.25 vs. 1.12, 1.09, 1.54 and 1.25 ng mL(-1)). Higher plasma 17β-estradiol level in S-RW versus SD-RW and SS-RW (10.94 vs. 7.18 and 6.72 pg mL(-1)) group was stated. The prolactin level was higher in plasma of S-RW versus D-RW and SS-RW (17.35 vs. 9.74 and 8.59 ng mL(-1)) rats. The effects of red wine drinking on the hormonal regulation of the male reproductive system depend on the type and the dose of red wine. Chemical compounds naturally occurring in red wines (i.e. phenolics) may modulate the effects of ethyl alcohol, but also directly affect the male reproduction.

  1. Effects of Fluoxetine and Visual Experience on Glutamatergic and GABAergic Synaptic Proteins in Adult Rat Visual Cortex123

    PubMed Central

    Beshara, Simon; Beston, Brett R.; Pinto, Joshua G. A.

    2015-01-01

    Abstract Fluoxetine has emerged as a novel treatment for persistent amblyopia because in adult animals it reinstates critical period-like ocular dominance plasticity and promotes recovery of visual acuity. Translation of these results from animal models to the clinic, however, has been challenging because of the lack of understanding of how this selective serotonin reuptake inhibitor affects glutamatergic and GABAergic synaptic mechanisms that are essential for experience-dependent plasticity. An appealing hypothesis is that fluoxetine recreates a critical period (CP)-like state by shifting synaptic mechanisms to be more juvenile. To test this we studied the effect of fluoxetine treatment in adult rats, alone or in combination with visual deprivation [monocular deprivation (MD)], on a set of highly conserved presynaptic and postsynaptic proteins (synapsin, synaptophysin, VGLUT1, VGAT, PSD-95, gephyrin, GluN1, GluA2, GluN2B, GluN2A, GABAAα1, GABAAα3). We did not find evidence that fluoxetine shifted the protein amounts or balances to a CP-like state. Instead, it drove the balances in favor of the more mature subunits (GluN2A, GABAAα1). In addition, when fluoxetine was paired with MD it created a neuroprotective-like environment by normalizing the glutamatergic gain found in adult MDs. Together, our results suggest that fluoxetine treatment creates a novel synaptic environment dominated by GluN2A- and GABAAα1-dependent plasticity. PMID:26730408

  2. Effects of Fluoxetine and Visual Experience on Glutamatergic and GABAergic Synaptic Proteins in Adult Rat Visual Cortex.

    PubMed

    Beshara, Simon; Beston, Brett R; Pinto, Joshua G A; Murphy, Kathryn M

    2015-01-01

    Fluoxetine has emerged as a novel treatment for persistent amblyopia because in adult animals it reinstates critical period-like ocular dominance plasticity and promotes recovery of visual acuity. Translation of these results from animal models to the clinic, however, has been challenging because of the lack of understanding of how this selective serotonin reuptake inhibitor affects glutamatergic and GABAergic synaptic mechanisms that are essential for experience-dependent plasticity. An appealing hypothesis is that fluoxetine recreates a critical period (CP)-like state by shifting synaptic mechanisms to be more juvenile. To test this we studied the effect of fluoxetine treatment in adult rats, alone or in combination with visual deprivation [monocular deprivation (MD)], on a set of highly conserved presynaptic and postsynaptic proteins (synapsin, synaptophysin, VGLUT1, VGAT, PSD-95, gephyrin, GluN1, GluA2, GluN2B, GluN2A, GABAAα1, GABAAα3). We did not find evidence that fluoxetine shifted the protein amounts or balances to a CP-like state. Instead, it drove the balances in favor of the more mature subunits (GluN2A, GABAAα1). In addition, when fluoxetine was paired with MD it created a neuroprotective-like environment by normalizing the glutamatergic gain found in adult MDs. Together, our results suggest that fluoxetine treatment creates a novel synaptic environment dominated by GluN2A- and GABAAα1-dependent plasticity.

  3. Effects of peripheral nerve injury on parvalbumin expression in adult rat dorsal root ganglion neurons.

    PubMed

    Medici, Tom; Shortland, Peter J

    2015-12-16

    Parvalbumin (PV) is a calcium binding protein that identifies a subpopulation of proprioceptive dorsal root ganglion (DRG) neurons. Calcitonin gene-related peptide (CGRP) is also expressed in a high proportion of muscle afferents but its relationship to PV is unclear. Little is known of the phenotypic responses of muscle afferents to nerve injury. Sciatic nerve axotomy or L5 spinal nerve ligation and section (SNL) lesions were used to explore these issues in adult rats using immunocytochemistry. In naive animals, the mean PV expression was 25 % of L4 or L5 dorsal root ganglion (DRG) neurons, and this was unchanged 2 weeks after sciatic nerve axotomy. Colocalization studies with the injury marker activating transcription factor 3 (ATF3) showed that approximately 24 % of PV neurons expressed ATF3 after sciatic nerve axotomy suggesting that PV may show a phenotypic switch from injured to uninjured neurons. This possibility was further assessed using the spinal nerve ligation (SNL) injury model where injured and uninjured neurons are located in different DRGs. Two weeks after L5 SNL there was no change in total PV staining and essentially all L5 PV neurons expressed ATF3. Additionally, there was no increase in PV-ir in the adjacent uninjured L4 DRG cells. Co-labelling of DRG neurons revealed that less than 2 % of PV neurons normally expressed CGRP and no colocalization was seen after injury. These experiments clearly show that axotomy does not produce down regulation of PV protein in the DRG. Moreover, this lack of change is not due to a phenotypic switch in PV immunoreactive (ir) neurons, or de novo expression of PV-ir in uninjured neurons after nerve injury. These results further illustrate differences that occur when muscle afferents are injured as compared to cutaneous afferents.

  4. Effects of Acupuncture, RU-486 on the Hypothalamic-Pituitary-Adrenal Axis in Chronically Stressed Adult Male Rats.

    PubMed

    Eshkevari, Ladan; Mulroney, Susan E; Egan, Rupert; Lao, Lixing

    2015-10-01

    We have recently reported that pretreatment with electroacupuncture (EA) at stomach meridian point 36 (St36) prevents the chronic cold-stress increase in the hypothalamus-pituitary-adrenal axis (HPA), an action that may be under central control. Given that treatment for stress-related symptoms usually begins after onset of the stress responses, the objectives of the present study were to determine the efficacy of EA St36 on HPA hormones when EA St36 is given after stress was initiated, if the results are long lasting, and if blocking the glucocorticoid receptor (GR) using RU-486 had the same effects as EA St36. Adult male rats were placed in 4 groups of animals, 3 of which were exposed to cold and 1 of which was a nontreatment control group. After exposure to the cold stress, 2 groups were treated with either EA St36 or sham-EA, repeated over 10 days. The increase in ACTH and corticosterone observed in stress-only rats was prevented in EA St36 animals, and the effects remained intact 4 days after withdrawal of EA but continuation of cold stress. When the GR was blocked with RU-486, the efficacy of EA St36 remained unchanged. GR blockade did significantly elevate ACTH, which is not seen with EA St36, suggesting that EA St36 does act centrally. The elevated HPA hormones in stress-only rats were associated with a significant increase in depressive and anxious behavior; this was not observed in the stressed EA St36 animals. The results indicate that EA specifically at St36 vs sham-EA is effective in treating chronic poststress exposure.

  5. Effect of a high or low ambient perinatal temperature on adult obesity in Osborne-Mendel and S5B/Pl rats.

    PubMed

    White, Christy L; Braymer, H Doug; York, David A; Bray, George A

    2005-05-01

    Perinatal environment is an important determinant of health status of adults. We tested the hypothesis that perinatal ambient temperature alters sympathetic activity and affects body composition in adult life and that this effect differs between S5B/Pl (S5B) and Osborne-Mendel (OM) strains of rat that were resistant (S5B) or susceptible (OM) to dietary obesity. From 1 wk before birth, rat litters were raised at either 18 or 30 degrees C until 2 mo of age while consuming a chow diet. Rats were then housed at normal housing temperature (22 degrees C) and provided either high-fat or low-fat diet. OM rats initially reared at 18 degrees C gained more weight on both diets than those reared at 30 degrees C. Perinatal temperature had no effect on body weight gain of the S5B rats on either diet. At 12 wk of age, OM and S5B rats reared at 18 degrees C had higher intakes of the high-fat diet than those reared at 30 degrees C but lower beta3-adrenergic receptor (beta3-AR) and uncoupling protein-1 (UCP1) mRNA levels in brown adipose tissue (BAT). The increase in metabolic rate in response to the beta3-agonist CL-316243, was greater in both OM and S5B rats reared at 18 degrees C than in those reared at 30 degrees C. Perinatal temperature differentially affects body weight in OM and S5B rats while having similar effects on food intake, response to a beta3-agonist, and BAT beta3-AR and UCP-1. The data suggest that OM rats are more susceptible to epigenetic programming than S5B rats.

  6. Differential effects of alprazolam and clonazepam on the immune system and blood vessels of non-stressed and stressed adult male albino rats

    PubMed Central

    Elmesallamy, Ghada E.; Abass, Marwa A.; Ahmed Refat, Nahla A.G.; Atta, Amal H.

    2011-01-01

    Benzodiazepines belongs to one of the most commonly used anxiolytic and anticonvulsant drugs in the world. Full description of toxic effects on different organs is lacking for nearly all the current benzodiazepines. The aim of the current work was to study the immunologic and vascular changes induced by sub-chronic administration of alprazolam and clonazepam in non-stressed and stressed adult male albino rats. Forty-two adult male albino rats were divided into 6 groups (I): (Ia) Negative control rats, (Ib): Positive control rats received distilled water, (II): Stressed rats, (III): Non-stressed rats received daily oral dose of clonazepam (0.5 mg/kg), (IV): Stressed rats received daily oral dose of clonazepam (0.5 mg/kg), (V): Non-stressed rats received daily oral dose of alprazolam (0.3 mg/kg). (VI): Stressed rats received daily oral dose of alprazolam (0.3 mg/kg). At the end of the 4th week, total leukocyte count (WBCs) and differential count were determined, anti-sheep RBC antibody (Anti-SRBC) titer and interleukin-2 (IL-2) level were assessed, thymus glands, lymph nodes, spleens and abdominal aortae were submitted to histopathological examination. Alprazolam was found to induce a significant increase in neutrophil count and a significant decrease in lymphocytes, anti-SRBC titer and IL-2 level with severe depletion of the splenic, thymal and nodal lymphocytes, accompanied by congestion and eosinophilic vasculitis of all organs tested in comparison to clonazepam treated rats. Stress enhanced the toxic effects. It was concluded that the immune system and blood vessels can be adversely affected to a greater extent by short-term chronic administration of alprazolam than by clonazepam, and these toxic effects are aggravated by stress. PMID:22058654

  7. Adolescent exposure to nicotine alters the aversive effects of cocaine in adult rats.

    PubMed

    Hutchison, Mary Anne; Riley, Anthony L

    2008-01-01

    Nicotine is one of the most commonly used drugs in adolescence and has been shown to alter the rewarding effects of cocaine when administered in adulthood. Although the abuse potential of a drug has been suggested to be a balance between its rewarding and aversive effects, the long-term effects of nicotine on the aversive properties of other drugs had not been studied. To that end, in the present study rats exposed to nicotine (0.4 mg/kg) during adolescence (postnatal days 35-44) were tested for the acquisition and extinction of a cocaine-induced conditioned taste aversion (10, 18 or 32 mg/kg) in adulthood. Conditioning consisted of four saccharin-drug pairings followed by six extinction trials. Although cocaine-induced aversions at all doses, no effect of nicotine preexposure was seen during acquisition. During extinction, the nicotine-preexposed groups conditioned with 10 and 18 mg/kg cocaine displayed a decreased rate of extinction compared to their respective controls. These results suggest that while adolescent nicotine exposure does not appear to directly alter the aversive properties of cocaine it may affect other processes related to the response to drugs given in adulthood.

  8. The ameliorative effect of thymol against hydrocortisone-induced hepatic oxidative stress injury in adult male rats.

    PubMed

    Aboelwafa, Hanaa R; Yousef, Hany N

    2015-08-01

    The aim of the present study was to investigate whether hydrocortisone induces oxidative stress in hepatocytes and to evaluate the possible ameliorative effect of thymol against such hepatic injury. Twenty-four adult male rats were divided into control, thymol, hydrocortisone, and hydrocortisone+thymol groups. The 4 groups were treated daily for 15 days. Hydrocortisone significantly induced oxidative stress in the liver tissues, marked by increased serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total oxidative capacity (TOC), and tumor necrosis factor-alpha (TNF-α) accompanied by marked decline of serum levels of total protein, albumin, and total antioxidant capacity (TAC). Also, marked elevation in the levels of the thiobarbituric acid reactive substances (TBARS) and TNF-α, beside significant decrease in the level of glutathione (GSH) in hepatic tissues were recorded. These biochemical alterations were accompanied by histopathological changes marked by destruction of the normal hepatic architecture, in addition to ultrastructural alterations represented by degenerative features covering almost all the cytoplasmic organelles of the hepatocytes. Supplementation of hydrocortisone-treated rats with thymol reversed most of the biochemical, histological, and ultrastructural alterations. The results of our study confirm that thymol has strong ameliorative effect against hydrocortisone-induced oxidative stress injury in hepatic tissues.

  9. Effects of perinatal bisphenol A exposure during early development on radial arm maze behavior in adult male and female rats

    PubMed Central

    Sadowski, Renee N.; Park, Pul; Neese, Steven L.; Ferguson, Duncan C.; Schantz, Susan L.; Juraska, Janice M.

    2014-01-01

    Previous work has shown that exposure to bisphenol A (BPA) can affect anxiety behavior. However, no studies have examined whether administration of this endocrine disruptor during the perinatal period has the potential to induce alterations in cognitive behavior in both adult males and females as assessed in an appetitive task. The goal of the current study was to determine whether exposure to different doses of BPA during early development alters performance on the 17-arm radial maze in adulthood in Long-Evans rats. Oral administration of corn oil (vehicle), 4 μg/kg, 40 μg/kg, or 400 μg/kg BPA to the dams occurred daily throughout pregnancy, and the pups received direct oral administration of BPA between postnatal days 1-9. Blood was collected from offspring at weaning age to determine levels of several hormones (thyroxine, thyroid stimulating hormone, follicle stimulating hormone, luteinizing hormone). One male and one female from each litter were evaluated on the 17-arm radial maze, a working/reference memory task, in adulthood. Results indicated that after exposure to BPA at both 4 and 400 μg/kg/day, rats of both sexes had decreased levels of FSH at weaning. There were no significant effects of BPA on performance on the radial arm maze in males or females. In conclusion, exposure to BPA during early development had modest effects on circulating hormones but did not affect a spatial learning and memory task. PMID:24440629

  10. Effects of maternal high-fat diet and sedentary lifestyle on susceptibility of adult offspring to ozone exposure in rats.

    PubMed

    Gordon, C J; Phillips, P M; Johnstone, A F M; Schmid, J; Schladweiler, M C; Ledbetter, A; Snow, S J; Kodavanti, U P

    2017-05-01

    Epidemiological and experimental data suggest that obesity exacerbates the health effects of air pollutants such as ozone (O3). Maternal inactivity and calorically rich diets lead to offspring that show signs of obesity. Exacerbated O3 susceptibility of offspring could thus be manifested by maternal obesity. Thirty-day-old female Long-Evans rats were fed a control (CD) or high-fat (HF) (60% calories) diet for 6 wks and then bred. GD1 rats were then housed with a running wheel (RW) or without a wheel (SED) until parturition, creating four groups of offspring: CD-SED, CD-RW, HF-SED and HF-RW. HF diet was terminated at PND 35 and all offspring were placed on CD. Body weight and %fat of dams were greatest in order; HF-SED > HF-RW > CD-SED > CD-RW. Adult offspring were exposed to O3 for two consecutive days (0.8 ppm, 4 h/day). Glucose tolerance tests (GTT), ventilatory parameters (plethysmography), and bronchoalveolar fluid (BALF) cell counts and protein biomarkers were performed to assess response to O3. Exercise and diet altered body weight and %fat of young offspring. GTT, ventilation and BALF cell counts were exacerbated by O3 with responses markedly exacerbated in males. HF diet and O3 led to significant exacerbation of several BALF parameters: total cell count, neutrophils and lymphocytes were increased in male HF-SED versus CD-SED. Males were hyperglycemic after O3 exposure and exhibited exacerbated GTT responses. Ventilatory dysfunction was also exacerbated in males. Maternal exercise had minimal effects on O3 response. The results of this exploratory study suggest a link between maternal obesity and susceptibility to O3 in their adult offspring in a sex-specific manner.

  11. PERINATAL EXPOSURE TO ESTROGENIC COMPOUNDS AND THE SUBSEQUENT EFFECTS ON THE PROSTRATE OF THE ADULT RAT: EVALUATION OF INFLAMMATION IN THE VENTRAL AND LATERAL LOBES

    EPA Science Inventory

    Perinatal exposure to estrogenic compounds and the subsequent effects on the prostate of the adult rat: evaluation of inflammation in the ventral and lateral lobes.

    Stoker TE, Robinette CL, Cooper RL.

    Endocrinology Branch, Reproductive Toxicology Division, National ...

  12. PERINATAL EXPOSURE TO ESTROGENIC COMPOUNDS AND THE SUBSEQUENT EFFECTS ON THE PROSTRATE OF THE ADULT RAT: EVALUATION OF INFLAMMATION IN THE VENTRAL AND LATERAL LOBES

    EPA Science Inventory

    Perinatal exposure to estrogenic compounds and the subsequent effects on the prostate of the adult rat: evaluation of inflammation in the ventral and lateral lobes.

    Stoker TE, Robinette CL, Cooper RL.

    Endocrinology Branch, Reproductive Toxicology Division, National ...

  13. Neurite regeneration in adult rat retinas exposed to advanced glycation end-products and regenerative effects of neurotrophin-4.

    PubMed

    Bikbova, Guzel; Oshitari, Toshiyuki; Yamamoto, Shuichi

    2013-10-09

    The purpose of this study was to determine the effect of low concentrations of advanced glycation end-products on neurite regeneration in isolated rat retinas, and to determine the effects of neurotrophin-4 on regeneration in advanced glycation end-products exposed retinas. Retinal explants of 4 adult Sprague-Dawley rats were cultured on collagen gel and were incubated in; (1) serum-free control culture media, (2) glucose-advanced glycation end-products-bovine serum albumin media, (3) glycolaldehyde-advanced glycation end-products-bovine serum albumin media, (4) glyceraldehyde-advanced glycation end-products-bovine serum albumin media, (5) glucose-advanced glycation end-products+neurotrophin-4 media, (6) glycolaldehyde-advanced glycation end-products+neurotrophin-4 media, or (7) glyceraldehyde-advanced glycation end-products+neurotrophin-4 supplemented culture media. After 7 days, the number of regenerating neurites from the explants was counted. Then, explants were fixed, cryosectioned, and stained for TUNEL. The ratio of TUNEL-positive cells to all cells in the ganglion cell layer was determined. Immunohistochemical examinations for the active-form of caspase-9 and apoptosis-inducing factor were performed. In retinas incubated with advanced glycation end-products containing media, the number of regenerating neurites were fewer than in retinas without advanced glycation end-products, and the number of TUNEL-positive cells and caspase-9- and apoptosis-inducing factor-immunopositive cells was significantly higher than in control media. Neurotrophin-4 supplementation increased the numbers of regenerating neuritis, and the number of TUNEL-positives, caspase-9-, and apoptosis-inducing factor-immunopositive cells were significantly fewer than that in advanced glycation end-products without neurotrophin-4 media. Low doses of advanced glycation end-products impede neurite regeneration in the rat retinas. Neurotrophin-4 significantly enhances neurite regeneration in

  14. Effects of neonatal handling on the basal forebrain cholinergic system of adult male and female rats.

    PubMed

    Pondiki, S; Stamatakis, A; Fragkouli, A; Philippidis, H; Stylianopoulou, F

    2006-10-13

    Neonatal handling is an early experience which results in improved function of the hypothalamic-pituitary-adrenal axis, increased adaptability and coping as a response to stress, as well as better cognitive abilities. In the present study, we investigated the effect of neonatal handling on the basal forebrain cholinergic system, since this system is known to play an important role in cognitive processes. We report that neonatal handling results in increased number of choline-acetyl transferase immunopositive cells in the septum/diagonal band, in both sexes, while no such effect was observed in the other cholinergic nuclei, such as the magnocellular preoptic nucleus and the nucleus basalis of Meynert. In addition, neonatal handling resulted in increased M1 and M2 muscarinic receptor binding sites in the cingulate and piriform cortex of both male and female rats. A handling-induced increase in M1 muscarinic receptor binding sites was also observed in the CA3 and CA4 (fields 3 and 4 of Ammon's horn) areas of the hippocampus. Furthermore, a handling-induced increase in acetylcholinesterase staining was found only in the hippocampus of females. Our results thus show that neonatal handling acts in a sexually dimorphic manner on one of the cholinergic parameters, and has a beneficial effect on BFCS function, which could be related to the more efficient and adaptive stress response and the superior cognitive abilities of handled animals.

  15. Effects of chronic oestradiol, progesterone and medroxyprogesterone acetate on hippocampal neurogenesis and adrenal mass in adult female rats.

    PubMed

    Chan, M; Chow, C; Hamson, D K; Lieblich, S E; Galea, L A M

    2014-06-01

    Both natural oestrogens and progesterone influence synaptic plasticity and neurogenesis within the female hippocampus. However, less is known of the impact of synthetic hormones on hippocampal structure and function. There is some evidence that the administration of the synthetic progestin, medroxyprogesterone acetate (MPA) is not as beneficial as natural progesterone and can attenuate oestrogen-induced neuroprotection. Although the effects of oestradiol have been well studied, little is known about the effects of natural and synthetic progestins alone and in combination with oestradiol on adult neurogenesis in females. In the present study, we investigated the effects of chronic oestradiol, progesterone, MPA and the co-administration of each progestin with oestradiol on neurogenesis within the dentate gyrus of adult ovariectomised female rats. Twenty-four hours after a bromodeoxyuridine (BrdU; 200 mg/kg) injection, female rats were repeatedly administered either progesterone (1 or 4 mg), MPA (1 or 4 mg), oestradiol benzoate (EB), progesterone or MPA in combination with EB (10 μg), or vehicle for 21 days. Rats were perfused on day 22 and brain tissue was analysed for the number of BrdU-labelled and Ki67 (an endogenous marker of cell proliferation)-expressing cells. EB alone and MPA + EB significantly decreased neurogenesis and the number of surviving BrdU-labelled cells in the dorsal region of the dentate gyrus, independent of any effects on cell proliferation. Furthermore, MPA (1 and 4 mg) and MPA + EB treated animals had significantly lower adrenal/body mass ratios and reduced serum corticosterone (CORT) levels. By contrast, progesterone + EB treated animals had significantly higher adrenal/body mass ratios and 1 mg of progesterone, progesterone + EB, and EB significantly increased CORT levels. The results of the present study demonstrate that different progestins alone and in combination with oestradiol can differentially affect neurogenesis (via cell survival

  16. Protective Effects of Edaravone in Adult Rats with Surgery and Lipopolysaccharide Administration-Induced Cognitive Function Impairment.

    PubMed

    Wang, Peiqi; Cao, Jiangbei; Liu, Na; Ma, Li; Zhou, Xueyue; Zhang, Hong; Wang, Yongan

    2016-01-01

    Postoperative cognitive dysfunction (POCD) is a clinical syndrome characterized by cognitive declines in patients after surgery. Previous studies have suggested that surgery contributed to such impairment. It has been proven that neuroinflammation may exacerbate surgery-induced cognitive impairment in aged rats. The free radical scavenger edaravone has high blood brain barrier permeability, and was demonstrated to effectively remove free radicals from the brain and alleviate the development of POCD in patients undergoing carotid endarterectomy, suggesting its potential role in preventing POCD. For this reason, this study was designed to determine whether edaravone is protective against POCD through its inhibitory effects on inflammatory cytokines and oxidative stress. First, Sprague Dawley adult male rats were administered 3 mg/kg edaravone intraperitoneally after undergoing a unilateral nephrectomy combined with lipopolysaccharide injection. Second, behavioral parameters related to cognitive function were recorded by fear conditioning and Morris Water Maze tests. Last, superoxide dismutase activities and malondialdehyde levels were measured in the hippocampi and prefrontal cortex on postoperative days 3 and 7, and microglial (Iba1) activation, p-Akt and p-mTOR protein expression, and synaptic function (synapsin 1) were also examined 3 and 7 days after surgery. Rats that underwent surgery plus lipopolysaccharide administration showed significant impairments in spatial and working memory, accompanied by significant reductions in hippocampal-dependent and independent fear responses. All impairments were attenuated by treatment with edaravone. Moreover, an abnormal decrease in superoxide dismutase activation, abnormal increase in malondialdehyde levels, significant increase in microglial reactivity, downregulation of p-Akt and p-mTOR protein expression, and a statistically significant decrease in synapsin-1 were observed in the hippocampi and prefrontal cortices of

  17. Protective Effects of Edaravone in Adult Rats with Surgery and Lipopolysaccharide Administration-Induced Cognitive Function Impairment

    PubMed Central

    Liu, Na; Ma, Li; Zhou, Xueyue; Zhang, Hong; Wang, Yongan

    2016-01-01

    Postoperative cognitive dysfunction (POCD) is a clinical syndrome characterized by cognitive declines in patients after surgery. Previous studies have suggested that surgery contributed to such impairment. It has been proven that neuroinflammation may exacerbate surgery-induced cognitive impairment in aged rats. The free radical scavenger edaravone has high blood brain barrier permeability, and was demonstrated to effectively remove free radicals from the brain and alleviate the development of POCD in patients undergoing carotid endarterectomy, suggesting its potential role in preventing POCD. For this reason, this study was designed to determine whether edaravone is protective against POCD through its inhibitory effects on inflammatory cytokines and oxidative stress. First, Sprague Dawley adult male rats were administered 3 mg/kg edaravone intraperitoneally after undergoing a unilateral nephrectomy combined with lipopolysaccharide injection. Second, behavioral parameters related to cognitive function were recorded by fear conditioning and Morris Water Maze tests. Last, superoxide dismutase activities and malondialdehyde levels were measured in the hippocampi and prefrontal cortex on postoperative days 3 and 7, and microglial (Iba1) activation, p-Akt and p-mTOR protein expression, and synaptic function (synapsin 1) were also examined 3 and 7 days after surgery. Rats that underwent surgery plus lipopolysaccharide administration showed significant impairments in spatial and working memory, accompanied by significant reductions in hippocampal-dependent and independent fear responses. All impairments were attenuated by treatment with edaravone. Moreover, an abnormal decrease in superoxide dismutase activation, abnormal increase in malondialdehyde levels, significant increase in microglial reactivity, downregulation of p-Akt and p-mTOR protein expression, and a statistically significant decrease in synapsin-1 were observed in the hippocampi and prefrontal cortices of

  18. Comparative effect of soy protein, soy isoflavones, and 17beta-estradiol on bone metabolism in adult ovariectomized rats.

    PubMed

    Cai, David J; Zhao, Yongdong; Glasier, Jennifer; Cullen, Diane; Barnes, Stephen; Turner, Charles H; Wastney, Meryl; Weaver, Connie M

    2005-05-01

    This study provided a comprehensive investigation on the effect of soy protein and soy isoflavones on both calcium and bone metabolism in virgin adult rats. The measurements included bone histology, calcium kinetic modeling, calcium balance, bone densitometry, and whole body densitometry. Results confirmed the bone-preserving effect of estrogen but did not support a bone-sparing role of soy isoflavones. Several animal and short-term human studies have indicated that soy protein isolate enriched with isoflavones may be used as an alternative therapy to estrogen replacement therapy. However, none of the previous studies have investigated this estrogenic effect on both calcium and bone metabolism in animals or humans, which is essential in ascertaining the mode of action of isoflavones. This study was designed to determine the effects of soy protein versus isoflavones on calcium and bone metabolism in an ovariectomized rat model. Unmated 6-month-old ovariectomized and sham-operated female Sprague-Dawley rats were randomly assigned to nine groups (16 rats/group) and pair-fed soy- or casein-based diets with or without isoflavones for 8 weeks. A reference group was administered estrogen through subcutaneous implants (20-35 pg/liter plasma). Bone densitometry, histomorphometry, and mechanical testing were used to study bone metabolism and quality. Calcium metabolism was studied using calcium tracer balance and kinetics. After ovariectomy, estrogen prevented bone loss in trabecular bone and suppressed formation on both trabecular and cortical bone surfaces. Isoflavones given as enriched soy protein isolate or supplements did not prevent trabecular bone loss. Combining isoflavones with estrogen had no additional benefits over estrogen alone. There were no differences in response to isoflavones caused by protein source. None of the treatments significantly affected either total Ca balance or (45)Ca absorption. However, soy protein showed significant effects on reducing

  19. Effects of exposure to extremely low frequency magnetic fields on spermatogenesis in adult rats.

    PubMed

    Duan, Weixia; Liu, Chuan; Wu, Hongjuan; Chen, Chunhai; Zhang, Tao; Gao, Peng; Luo, Xue; Yu, Zhengping; Zhou, Zhou

    2014-01-01

    The constant exposure of modern society to extremely low frequency magnetic fields (ELF-MF) has raised considerable concerns about the potential risks to male reproduction. However, the epidemiological and experimental data remain contradictory and inconclusive. In the present study, we investigated the effects of 50 Hz ELF-MF of 500 µT applied 4 h/day, 7 days/week for 4 and 8 weeks on male reproduction, focusing on changes in spermatogenesis. Several biological endpoints related to testicular function and spermatogenesis were measured, including the following: body mass, masses of testes and epididymis, sperm count and abnormal sperm ratio in the caudal epididymis, serum testosterone level, testicular histology, frequency of 14 stages of the cycle of the seminiferous epithelium and of four stages of meiosis I, germ cell apoptosis and testicular oxidative status. No significant differences were found in the biological endpoints between the sham control and the exposed rats in either the 4- or 8-week exposure period. These negative results may result from the lack of change in serum testosterone. In conclusion, our study indicates that exposure to low intensity ELF-MF may have no adverse effects on spermatogenesis.

  20. Differential behavioural and neurochemical outcomes from chronic paroxetine treatment in adolescent and adult rats: a model of adverse antidepressant effects in human adolescents?

    PubMed

    Karanges, Emily; Li, Kong M; Motbey, Craig; Callaghan, Paul D; Katsifis, Andrew; McGregor, Iain S

    2011-05-01

    Selective serotonin reuptake inhibitor use is associated with increased risk of suicidal ideation in adolescent humans, yet the neuropharmacological basis of this phenomenon is unknown. Consequently, we examined the behavioural and neurochemical effects of chronic paroxetine (PRX) treatment in adult and adolescent rats. Rats received PRX in their drinking water (target dose 10 mg/kg) for 22 d, during which time they were assessed for depression- and anxiety-like behaviours. Subsequent ex-vivo analyses examined serum PRX concentrations, striatal neurotransmitter content, and regional serotonin and dopamine transporter (SERT, DAT) binding density. After 11-12 d treatment, PRX-treated adolescent rats showed a significant inhibition of social interaction while adults were unaffected. After 19-20 d treatment, adolescents failed to show an antidepressant-like effect of PRX treatment on the forced swim test (FST), while PRX-treated adults showed a typical decrease in immobility and increase in swimming. Two PRX-treated adolescents died unexpectedly after the FST suggesting a compromised response to physical stress. Despite their greater apparent adverse reaction to the drug, adolescents had significantly lower plasma PRX than adults at day 22 of treatment. Chronic PRX treatment had similar effects in adults and adolescents on striatal 5-HT (unchanged relative to controls) and 5-HIAA levels (decreased), while markers of dopaminergic function (DOPAC, HVA, DA turnover) were increased in adults only. SERT density was up-regulated in the amygdala in PRX-treated adolescents only while DAT density in the nucleus accumbens was down-regulated only in PRX-treated adults. These data suggest that the immature rat brain responds differently to PRX and that this might be of use in modelling the atypical response of human adolescents to antidepressants. The age-specific PRX-induced changes in dopaminergic markers and SERT and DAT binding provide clues as to the neural mechanisms

  1. Comparison of some behavioral effects of d- and l-methamphetamine in adult male rats.

    PubMed

    Siemian, Justin N; Xue, Zhaoxia; Blough, Bruce E; Li, Jun-Xu

    2017-07-01

    Both l- and d-methamphetamine (l- and d-MA) are more potent to release norpepinephrine (NE) than dopamine, and the selectivity is greater for l-MA than d-MA. Little is known of the in vivo pharmacology of l-MA. This study compared the effects of l-MA and d-MA in assays of nociception, behavioral disruption, and impulsivity. Antinociceptive effects of d- and l-MA were examined in two pain assays: the warm water tail withdrawal test for acute nociception and the von Frey test in complete Freund's adjuvant (CFA)-treated rats for chronic inflammatory pain. Food-maintained operant responding and locomotion tests were used to assess generalized behavioral disruption. The 5-choice serial reaction time test (5-CSRTT) was used to assess drug-induced effects on impulse control. A delay discounting procedure was used to determine drug-induced changes in sensitivity to reinforcer delay (impulsive choice). l-MA (3.2-10 mg/kg) produced dose-dependent antinociception in both pain assays, decreased the rate of food-maintained operant responding, and decreased locomotor activity at a higher dose (17.8 mg/kg). In contrast, d-MA (0.32-3.2 mg/kg) did not produce antinociception in either assay, produced biphasic effects on response rate, and increased locomotor activity. In the 5-CSRTT, d-MA but not l-MA produced significant increase in premature responses. In the delay discounting procedure, both drugs did not affect the delay function at doses that did not increase omissions. These data suggest that d- and l-MA have different behavioral profiles. Consideration should be given to these differences in future studies when l-MA is proposed for potential therapies.

  2. Effect of cross-fostering on seizures in adult male offspring of methamphetamine-treated rat mothers.

    PubMed

    Slamberová, R; Hrubá, L; Bernásková, K; Matejovská, I; Rokyta, R

    2010-10-01

    Stimulant drugs are often associated with increased seizure susceptibility. Inhibitory gamma-aminobutyric acid (GABA) and excitatory N-methyl-D-aspartate (NMDA) systems play a role in the effect of stimulants in the genesis of epileptic seizures. Our previous studies showed that prenatal methamphetamine (MA) exposure induced long-term changes in seizure susceptibility. The aim of the present study was to investigate the effect of cross-fostering on the prenatal and postnatal MA-exposed rats, respectively, on their seizures in adulthood. Bicuculline (GABA(A) receptor antagonist), NMDA (NMDA receptor agonist) and flurothyl (a convulsant gas) were used to induce seizures in adult male offsprings. Female dams were injected with MA (5 mg/kg daily) or physiological saline (S) for approx. 9 week [about 3 week prior to impregnation, for the entire gestation period (22 days) and in preweaning period (21 days)]. Absolute controls (C) did not receive any injections. On postnatal day 1, pups were cross-fostered so that each mother received pups from all three treatments. Thus, nine groups (based on the prenatal and postnatal drug exposure) of adult male rats were tested in each seizure test: C/C; C/S; C/MA; S/C; S/S; S/MA; MA/C; MA/S; MA/MA. The present study demonstrates that the effect of prenatal and/or postnatal MA exposure is seizure model specific. In addition, our data show that there is an effect of cross-fostering on seizures; particularly, the effect of prenatal MA exposure shown in animals fostered by control mothers is no longer apparent in animals fostered postnatally by MA-treated mothers. Such effect of postnatal treatment is not manifested in prenatal controls. In summary, it seems that: (1) prenatal MA exposure alters seizure susceptibility more than postnatal MA exposure; (2) especially in seizures induced by chemicals that affect GABAergic system (bicuculline, flurothyl) notable effect of adoption (cross-fostering) is apparent; (3) in seizure models that are

  3. Effect of neonatal or adult heat acclimation on testicular and epididymal morphometry and sperm production in rats.

    PubMed

    Kurowicka, B; Dietrich, G J; Kotwica, G

    2015-03-01

    The accessory gland weight, testicular and epididymal morphometry and sperm production were analyzed in four groups of rats housed at 20 or 34°C: (1) control rats (CR) kept at 20°C from birth to day 90; (2) adult heat-acclimated rats (AHA) kept at 20°C from birth to day 45 followed by 34°C to day 90; (3) neonatal heat-acclimated rats (NHA) kept at 34°C from birth to day 90 and (4) de-acclimated rats (DA) kept at 34°C from birth to day 45 followed by 20°C to day 90. In NHA and DA rats, accessory gland weight was higher than in controls. Despite the lack of differences in testicular and epididymal morphometry, curvilinear velocity of spermatozoa was lower in the NHA group compared to controls. Areas of seminiferous tubules were lower in the DA than in CR and NHA groups, however, sperm concentration and motility were not affected by the treatment in this group. In AHA rats, epithelium of approximately 20% of seminiferous tubules was degenerated and Sertoli cell number was lower in the remaining tubules. In contrast to sperm motility, epididymal duct area, area of the duct occupied by spermatozoa and cauda epididymis sperm concentration were lower in AHA rats than in the other groups. In conclusion, neonatal heat acclimation did not affect the testicular morphometry and epididymal sperm concentration, suggesting adjustment to high ambient temperature. On the contrary, adult heat acclimation of rats affected the examined parameters, leading to decreased sperm concentration.

  4. Fructose supplementation worsens the deleterious effects of short-term high-fat feeding on hepatic steatosis and lipid metabolism in adult rats.

    PubMed

    Crescenzo, Raffaella; Bianco, Francesca; Coppola, Paola; Mazzoli, Arianna; Tussellino, Margherita; Carotenuto, Rosa; Liverini, Giovanna; Iossa, Susanna

    2014-09-01

    The purpose of the present study was to examine the short-term effect of high-fat or high-fat-high-fructose feeding on hepatic lipid metabolism and mitochondrial function in adult sedentary rats. Adult male rats were fed a high-fat or high-fat-high-fructose diet for 2 weeks. Body and liver composition, hepatic steatosis, plasma lipid profile and hepatic insulin sensitivity, together with whole-body and hepatic de novo lipogenesis, were assessed. Hepatic mitochondrial mass, functionality, oxidative stress and antioxidant defense were also measured. Rats fed the high-fat-high-fructose diet exhibited significantly higher plasma triglycerides, non-esterified fatty acids, insulin and indexes of hepatic insulin resistance compared with rats fed a low-fat or a high-fat diet. Hepatic triglycerides and ceramide, as well as the degree of steatosis and necrosis, were significantly higher, while liver p-Akt was significantly lower, in rats fed high-fat-high-fructose diet than in rats fed high-fat diet. A significant increase in non-protein respiratory quotient and hepatic fatty acid synthase and stearoyl CoA desaturase activity was found in rats fed the high-fat-high-fructose diet compared with those fed the high-fat diet. Significantly lower mitochondrial oxidative capacity but significantly higher oxidative stress was found in rats fed high-fat and high-fat-high-fructose diets compared with rats fed low-fat diet, while mitochondrial mass significantly increased only in rats fed high-fat-high-fructose diet. In conclusion, short-term consumption of a Western diet, rich in saturated fats and fructose, is more conducive to the development of liver steatosis and deleterious to glucose homeostasis than a high-fat diet. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  5. Long-Term Effects of Chronic Buspirone during Adolescence Reduce the Adverse Influences of Neonatal Inflammatory Pain and Stress on Adaptive Behavior in Adult Male Rats

    PubMed Central

    Butkevich, Irina P.; Mikhailenko, Viktor A.; Vershinina, Elena A.; Aloisi, Anna M.; Barr, Gordon A.

    2017-01-01

    Neonatal pain and stress induce long-term changes in pain sensitivity and behavior. Previously we found alterations in pain sensitivity in adolescent rats exposed to early-life adverse events. We tested whether these alterations have long-lasting effects and if those effects can be improved by the 5-hydroxytryptamine 1A (5-HT1A) receptor agonist buspirone injected chronically during the adolescent period. This study investigates: (1) effects of inflammatory pain (the injection of formalin into the pad of a hind paw) or stress (short maternal deprivation-isolation, MI), or their combination in 1–2-day-old rats on the adult basal pain, formalin-induced pain, anxiety and depression; (2) effects of adolescent buspirone in adult rats that experienced similar early-life insults. Changes in nociceptive thresholds were evaluated using the hot plate (HP) and formalin tests; levels of anxiety and depression were assessed with the elevated plus maze and forced swim tests respectively. Both neonatal painful and stressful treatments induced long-term alterations in the forced swim test. Other changes in adult behavioral responses were dependent on the type of neonatal treatment. There was a notable lack of long-term effects of the combination of early inflammatory pain and stress of MI on the pain responses, anxiety levels or on the effects of adolescent buspirone. This study provides the first evidence that chronic injection of buspirone in adolescent rats alters antinociceptive and anxiolytic effects limited to adult rats that showed behavioral alterations induced by early-life adverse treatments. These data highlight the role of 5-HT1A receptors in long-term effects of neonatal inflammatory pain and stress of short MI on adaptive behavior and possibility of correction of the pain and psychoemotional behavior that were altered by adverse pain/stress intervention using buspirone during critical adolescent period. PMID:28184190

  6. Long-Term Effects of Chronic Buspirone during Adolescence Reduce the Adverse Influences of Neonatal Inflammatory Pain and Stress on Adaptive Behavior in Adult Male Rats.

    PubMed

    Butkevich, Irina P; Mikhailenko, Viktor A; Vershinina, Elena A; Aloisi, Anna M; Barr, Gordon A

    2017-01-01

    Neonatal pain and stress induce long-term changes in pain sensitivity and behavior. Previously we found alterations in pain sensitivity in adolescent rats exposed to early-life adverse events. We tested whether these alterations have long-lasting effects and if those effects can be improved by the 5-hydroxytryptamine 1A (5-HT1A) receptor agonist buspirone injected chronically during the adolescent period. This study investigates: (1) effects of inflammatory pain (the injection of formalin into the pad of a hind paw) or stress (short maternal deprivation-isolation, MI), or their combination in 1-2-day-old rats on the adult basal pain, formalin-induced pain, anxiety and depression; (2) effects of adolescent buspirone in adult rats that experienced similar early-life insults. Changes in nociceptive thresholds were evaluated using the hot plate (HP) and formalin tests; levels of anxiety and depression were assessed with the elevated plus maze and forced swim tests respectively. Both neonatal painful and stressful treatments induced long-term alterations in the forced swim test. Other changes in adult behavioral responses were dependent on the type of neonatal treatment. There was a notable lack of long-term effects of the combination of early inflammatory pain and stress of MI on the pain responses, anxiety levels or on the effects of adolescent buspirone. This study provides the first evidence that chronic injection of buspirone in adolescent rats alters antinociceptive and anxiolytic effects limited to adult rats that showed behavioral alterations induced by early-life adverse treatments. These data highlight the role of 5-HT1A receptors in long-term effects of neonatal inflammatory pain and stress of short MI on adaptive behavior and possibility of correction of the pain and psychoemotional behavior that were altered by adverse pain/stress intervention using buspirone during critical adolescent period.

  7. The lack of protective effects of tea supplementation on liver and jejunal epithelium in adult rats exposed to cadmium and lead.

    PubMed

    Tomaszewska, Ewa; Winiarska-Mieczan, Anna; Dobrowolski, Piotr

    2015-11-01

    Adult rats at the age of 12 weeks were divided into the control group and groups supplemented with green (GT), black (BT), red (RT), or white (WT) tea extracts. The diet (except that for the control) was mixed with 7 mg Cd/kg and 50 mg Pb/kg. The experiment lasted 12 weeks. Basal haematology and plasma biochemical parameters as well as the histomorphometrical parameters of jejunal epithelium and liver were determined. The lowest body mass was found in the RT and WT groups. Some functional (increased plasma ALT and AST, and the de Ritis coefficient) and structural changes in the liver (slight fatty degenerative changes, an increase in the intercellular space) were evident irrespective of the type of tea in the Cd and Pb poisoned rats. This toxic effect was visible especially in rats drinking black or red tea. However, the rats had no elevated LDH and ALT activities. The highest content of Cd and Pb in the liver and blood plasma was found in rats drinking red tea. Based on the results obtained, it is clear that long-term exposure of adult rats with a mature intestinal barrier to Cd and Pb contamination, under higher exposure conditions than the current estimates of weekly exposure of the general population to Cd and Pb through diet, causes a toxic effect, especially in the liver, and can change the structure of intestinal mucosa, irrespective of tea administration.

  8. Rotenone exerts similar stimulatory effects on H2O2 production by isolated brain mitochondria from young-adult and old rats.

    PubMed

    Michelini, Luiz G B; Figueira, Tiago R; Siqueira-Santos, Edilene S; Castilho, Roger F

    2015-03-04

    Chronic and systemic treatment of rodents with rotenone, a classical inhibitor of mitochondrial respiratory complex I, results in neurochemical, behavioral, and neuropathological features of Parkinson's disease. The aim of the present study was to evaluate whether brain mitochondria from old rats (24 months old) would be more susceptible to rotenone-induced inhibition of oxygen consumption and increased generation of H2O2 than mitochondria from young-adult rats (3-4 months old). Isolated brain mitochondria were incubated in the presence of different rotenone concentrations (5, 10, and 100nM), and oxygen consumption and H2O2 production were measured during respiratory states 3 (ADP-stimulated respiration) and 4 (resting respiration). Respiratory state 3 and citrate synthase activity were significantly lower in mitochondria from old rats. Mitochondria from young-adult and old rats showed similar sensitivity to rotenone-induced inhibition of oxygen consumption. Similarly, H2O2 production rates by both types of mitochondria were dose-dependently stimulated to the same extent by increasing concentrations of rotenone. We conclude that rotenone exerts similar effects on oxygen consumption and H2O2 production by isolated brain mitochondria from young-adult and old rats. Therefore, aging does not increase the mitochondrial H2O2 generation in response to complex I inhibition. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Effects of low and high deprenyl dose on antioxidant enzyme activities in the adult rat brain.

    PubMed

    Lalkovicova, Maria; Horvathova, Frantiska; Sulla, Igor; Mihalik, Jozef; Danielisova, Viera

    2017-01-01

    We evaluated the effects of low dose deprenyl (LDD, 0.0025 mg/kg per day) and high dose deprenyl (HDD, 0.25 mg/kg per day) treatment of male Wistar rats for 30 days on the activities of SOD and CAT in the cortex, striatum, and hippocampus. Total SOD and MnSOD activities were increased with LDD (p <0.05) in the cortex (0.74 ± 0.03; 0.31 ± 0.02), striatum (0.75 ± 0.02; 0.27 ± 0.03) and CA1 region of the hippocampus (0.75 ± 0.02; 0.29 ± 0.03) compared to the control (0.53 ± 0.02; 0.15 ± 0.02), but reduced (p <0.05) with HDD compared to the LDD group. CAT activity was increased (p <0.05) with LDD in the cortex (27.34 ± 3.11), striatum (22.22 ± 1.85), and hippocampal CA1 region (16.62 ± 2.15) compared to control (10.33 ± 1.01), while a decrease was induced by HDD in the striatum (9.85 ± 1.09) compared to LDD. There was a significant (p <0.05) difference in number of Fluoro Jade B positive CA1 neurons induced by LDD (21.14 ± 2.85%) and HDD (12.61 ± 1.42%), as well as the number of NeuN positive CA1 neurons after LDD (183.35 ± 11.14 cells/mm) and HDD (238.45 ± 14.11 cells/mm (p < 0.05). Deprenyl showed a potential in improving the neurological outcome and reducing the oxidative damage.

  10. Effect of green tea (Camellia sinensis L.) extract on morphological and functional changes in adult male gonads of albino rats.

    PubMed

    Chandra, Amar K; Choudhury, Shyamosree Roy; De, Neela; Sarkar, Mahitosh

    2011-09-01

    Green tea, prepared from the steamed and dried leaves of the shrub Camellia sinensis, is known for its antioxidant and anti-carcinogenic effects. However, its effects on male gonadal functions have not been explored adequately and the present investigation has been undertaken to evaluate the effect of green tea extract on gonads of adult male albino rats. Results of in vivo studies showed that green tea extract (GTE) at mild (1.25 g%, identical to 5 cups of tea/day), moderate (2.5 g%, identical to 10 cups of tea/day) and high (5.0 g%, identical to 20 cups of tea/day) doses, for a period of 26 days, altered morphology and histology of testis and accessory sex organs. A significant dose-dependent decrease in the sperm counts, inhibited activities of testicular delta(5)3beta-and 17beta-hydroxysteroid dehydrogenase (delta5-3beta3-HSD and 17beta3-HSD respectively) and decreased serum testosterone level were noticed. Significant increase in serum LH level was observed after moderate and high doses; serum FSH level also increased but not significantly. Histopathological examination showed inhibition of spermatogenesis evidenced by preferential loss of matured and elongated spermatids. Results of this study showed that GTE at relatively high dose may cause impairment of both the morphological and normal functional status of testis in rodents and thus its consumption at relatively high doses raises concern on male reproductive function in spite of its other beneficial effects.

  11. Evaluation of amygdaloid neuronal dendritic arborization enhancing effect of Centella asiatica (Linn) fresh leaf extract in adult rats.

    PubMed

    Mohandas Rao, K G; Rao, Muddanna S; Rao, Gurumadhva S

    2012-12-03

    OBJECTIVE: Centella asiatica (CeA), a creeper, growing in moist places in India and other Asian countries. Leaves of CeA are used for memory enhancement in Ayurvedic system of medicine, an alternative system of medicine originated from India. In the present study, we have investigated the role of CeA fresh leaf extract treatment on adult rats on dendritic morphology of amygdaloid neurons, one of the regions concerned with learning and memory. METHODS: Adult rats (2.5-month old) were fed with 2, 4 and 6 mL/(day kg) of fresh leaf extract of CeA for 2, 4 and 6 weeks. After the treatment period the rats were killed, brains were removed and amygdaloid neurons were impregnated with silver nitrate (Golgi staining). Such silver impregnated amygdaloid neurons were traced using camera lucida and dendritic branching points (a measure of dendritic arborization) and intersections (a measure of dendritic length) were quantified. These data were compared with those of age matched control rats. RESULTS: The results showed a significant increase in the dendritic length (intersections) and dendritic branching points in amygdaloid neurons of the rats treated with higher dose [6 mL/(day·kg)] of CeA for longer period of time (i.e. 6 weeks). CONCLUSIONS: Constituents/active principles present CeA fresh leaf extract has neuronal dendritic growth stimulating property; hence it can be used for enhancing neuronal dendrites in stress and other neurodegenerative and memory disorders.

  12. Protective effects of the antihistamine promethazine aginst acute paraxon-methyl and dicrotophos toxicity in adult rats

    PubMed Central

    Nurulain, Syed M; Ojha, Shreesh; Shafiullah, Mohammad; Khan, Nadia; Oz, Murat; Sadek, Bassem

    2015-01-01

    Organophosphorus compound poisoning (OPC) is a global issue. The problem is aggravated with the threats of terrorist use, unintentional use and irresponsible practice as happened recently in turmoil countries. The purpose of the current study was to investigate the old-generation antihistamine promethazine (PROM), a drug with multi pharmacological actions, as an antidote to extremely and highly toxic (WHO’s class IA and IB) OPC poisoning in experimental animal models conducted on adult male wistar rats. Experimental groups were treated intraperitoneal (i.p.) with LD70 of methyl paraoxon (MPOX), class IA and dicrotophos (DCP), class IB alone and a combination of simultaneously i.p. injection of PROM. Mortality was recorded at 30 minutes, 1, 2, 3, 4, 24, 48 hours post injections. RBC-AChE was measured in survivals. MPOX was chosen for further studies with atropine (ATR) and pralidoxime (PAM). In addition to Kaplan-Meir survival analysis, serum lactate dehydrogenase (LDH) and creatinine kinase (CK) from serum were measured in all experimental groups with MPOX. The results revealed significant protection by PROM in both MPOX and DCP intoxicated rats, though the inhibition of RBC-AChE was high. The observed results show that groups treated with a combination of MPOX and PROM or MPOX, PROM, and PAM were protected higher than those treated with MPOX and ATR or MPOX, ATR, and PAM though statistically not significantly different (P ≤ 0.05). No effect was observed on the activity of LDH and CK. The study concludes that PROM may be effectively used in OPC poisoning. However, risk/benefits trials and further studies with different doses and other OPC groups are warranted. PMID:26770383

  13. Long-term effects of early diazepam exposure on social differentiation in adult male rats subjected to the diving-for-food situation.

    PubMed

    Schroeder, H; Toniolo, A M; Nehlig, A; Desor, D

    1998-10-01

    The present study was designed to investigate the consequences of a chronic diazepam (DZ) exposure (10 mg/kg/day) during the first 3 weeks of life on social behavior of adult male rats measured in a situation of restricted access to food, the diving-for-food model. The treatment had no long-term effects on the acquisition of social roles related to feeding. However, DZ-exposed rats were less efficient than controls in carrying food from the feeder to the cage during the 1st session but were able to adapt and improve their performances during the 2nd one. In the home cage, DZ-exposed rats were more aggressive toward conspecifics than controls and compensated for their deficit of food by stealing it from the others. These results suggest that an early DZ exposure has long-term consequences on social behavior of rats, possibly reflecting a reduction of the level of emotionality.

  14. Effects of environmental enrichment on anxiety responses, spatial memory and cytochrome c oxidase activity in adult rats.

    PubMed

    Sampedro-Piquero, P; Zancada-Menendez, C; Begega, A; Rubio, S; Arias, J L

    2013-09-01

    We have studied the effect of an environmental enrichment (EE) protocol in adult Wistar rats on the activity in the elevated zero-maze (EZM), performance in the radial-arm water maze (RAWM) and we have also examined the changes in the neuronal metabolic activity of several brain regions related to anxiety response and spatial memory through cytochrome c oxidase histochemistry (COx). Our EE protocol had anxiolytic effect in the EZM; the animals spent more time and made more entries into the open quadrants, they had lower latency to enter into the open quadrant and lower levels of defecation. Also, the EE group showed fewer working memory and reference memory errors, as well as lesser distance travelled in the first day of the spatial training. In relation to the neuronal metabolic activity, EE reduced the COx activity in brain regions related to anxiety response, such as the infralimbic cortex, the paraventricular thalamic and hypothalamic nucleus, the basolateral amygdala, and the ventral hippocampus. Interestingly, there were no significant differences between groups in the dorsal hippocampus, more related to spatial cognition. These results suggest a beneficial effect of EE on spatial memory as a result of reducing anxiety levels and the COx activity in brain regions involved in anxiety response. We also found a differential pattern of activation inside the hippocampus, suggesting that the dorsal hippocampus has a preferential involvement in spatial learning and memory, whereas the ventral hippocampus has a role in anxiety response.

  15. Effects of repeated ether stress on the hypothalamic-pituitary-testes axis in adult rats with special reference to inhibin secretion.

    PubMed

    Tohei, A; Tomabechi, T; Mamada, M; Akai, M; Watanabe, G; Taya, K

    1997-05-01

    Effects of ether stress on the hypothalamo-hypophysial-gonadal axis in adult male rats were examined. To clarify the role of adrenal glucocorticoids in gonadal function, the effects of adrenalectomy and Dexamethasone treatment were also investigated. Ether stress increased the plasma concentrations of ACTH and corticosterone, but decreased the plasma concentrations of LH, FSH, inhibin and testosterone. The pituitary responsiveness to LH-RH for LH release and testicular responsiveness to the endogenous LH for testosterone release were maintained in stressed rats. Adrenalectomy caused an increase in the plasma concentrations of ACTH, but decreased the plasma concentrations of LH, FSH and testosterone. Dexamethasone treatment in adrenalectomized rats recovered the levels of plasma gonadotropins to control levels. The concentration of plasma inhibin did not change in adrenalectomized rats, but it was decreased compared to control rats by Dexamethasone treatment. Treatments of Dexamethasone in intact male rats resulted in a decline in plasma levels of testosterone and inhibin without a decrease in the levels of LH and FSH, indicating the direct effect of Dexamethasone on the testes. These results indicate that increased ACTH secretion in stressed rats is probably due to hypersecretion of CRH from the hypothalamus, which suppresses gonadotropin secretion via the inhibition of LH-RH. The decreased levels of testosterone may be caused by a stress-induced decrease in plasma LH concentrations and increased secretion of corticosterone in the ether stressed rats. The low levels of plasma inhibin in stressed rats was also probably due to the direct effect of corticosterone on the Sertoli cells.

  16. The effects of different levels of peppermint alcoholic extract on body-weight gain and blood biochemical parameters of adult male Wistar rats

    PubMed Central

    Mesbahzadeh, Behzad; Akbari, Mohsen; kor, Nasroallah Moradi; Zadeh, Jalal Bayati

    2015-01-01

    Introduction Peppermint is an efficient medicinal plant for the treatment of diseases, and it also can be used to produce raw materials in the pharmaceutical industry. The purpose of the current study was to evaluate the effects of various levels of peppermint alcoholic extract on body-weight gain and blood biochemical parameters in adult male Wistar rats. Methods This experiment was conducted using a completely randomized design (CRD). Fifty adult, healthy, male Wistar rats (ages of 2.5–3 months; weights of 190–210 g) were allocated randomly into five groups. T1 was the control group in which the rats received 0.3 ml of distilled water). Groups T2, T3, T4, and T5 received 75, 150, 300, and 600 mg/kg of peppermint extract, respectively. The rats received daily pretreatment by oral gavages for 21 days. We recorded body weights at the beginning and at the end of the study to determine the changes in the body weights. Blood samples were collected for the measurement of glucose, cholesterol, triglycerides, HDL, LDL, albumin, globulin, and total protein. Statistical analysis of the data was done by SAS software. The data statistically analyzed using one-way analysis of variance (ANOVA), which was conducted through Dennett’s multiple comparison post-test. Results The results indicated that the rats treated with peppermint gained more weight (p < 0.05) and also decreased the serum concentrations of triglycerides, total cholesterol, LDL, and glucose in T3, T4 and T5 than the other groups (p < 0.05). Conclusion Peppermint extract had a positive effect on body-weight gain and some blood parameters in adult male Wistar rats. The findings showed that peppermint is a crucial substance at high temperature, and future research should be focused on determining the details of the mechanisms involved in producing the observed effects of peppermint extract. PMID:26516445

  17. Effect of cigarette smoke on body weight, food intake and reproductive organs in adult albino rats.

    PubMed

    Audi, Sumedha S; Abraham, Marjorie E; Borker, Abhaya S

    2006-07-01

    One hour daily exposure to cigarette smoke for two months significantly decreased the body weight and food intake in male and female albino rats. The latency for conception increased significantly and the litter size decreased. Mortality rate per litter increased and grayish discoloration of the skin in the experimental group was the only congenital anomaly seen. Testes and ovaries showed a significant decrease in weight. The stroma of the ovaries were occupied by very few Graafian follicles. Testes showed disruption of the normal orderly progression of the spermatogonia. The tubules showed only one layer of spermatogonia and very few germinal cells. The number of sperms was less in the testes. The results show that exposure to cigarette smoke is detrimental to the reproductivity in both, male and female albino rats.

  18. Histopathological effects of sub-chronic lamivudine-artesunate co-administration on the liver of diseased adult Wistar rats

    PubMed Central

    Olurishe, Temidayo Olutoyin; Kwanashie, Helen Ochuko; Anuka, Joseph; Muktar, Haruna; Bisalla, Mohammed

    2011-01-01

    Background: Lamivudine and artesunate are sometimes co administered in HIV-malaria co morbidity. Both drugs are used concurrently in presumptive malaria treatment and simultaneous HIV post exposure prophylaxis. Aim: The aim of this study was to investigate the effect of lamivudine-artesunate co administration on the histology of the liver of diseased adult Wistar rats. Materials and Methods: Five groups of rats of both sexes were used for the study and placed on feed and water ad libitum. Disease state consisted of immunosuppression with cyclophosphamide, and infection with Plasmodium berghei. Group 1 animals served as vehicle control, while group 2 were the diseased controls. Group 3 animals received 20 mg/kg lamivudine for three weeks, while group 4 similarly received 20 mg/kg Lamivudine but also received 10 mg/kg artesunate from day 12. Animals in group 5 received 10 mg/kg artesunate from day 12. All drugs were administered intraperitoneally. The animals were treated for twenty-one days, at the end of which they were sacrificed and their livers fixed in 10% formalin for histological studies. Result: Results from the study show the presence of regions of focal necrosis and perivascular cuffing with animals that received artesunate. Hemosiderosis was a common feature in all the parasitized groups, while fatty degeneration was observed in the group that received artesunate alone. Conclusion: Concurrent lamivudine-artesunate administration resulted in some histopathological changes in the liver. This study suggests there may be considerable histological changes with repeated occurrence of malaria and immunosuppression that may warrant intermittent lamivudine-artesunate administration, and may require evaluation as well as monitoring of liver function during such therapeutic interventions. PMID:22540106

  19. A comparative study of the effect of diet and soda carbonated drinks on the histology of the cerebellum of adult female albino Wistar rats.

    PubMed

    Eluwa, M A; Inyangmme, I I; Akpantah, A O; Ekanem, T B; Ekong, M B; Asuquo, O R; Nwakanma, A A

    2013-09-01

    Carbonated drinks are widely consumed because of their taste and their ability to refresh and quench thirst. These carbonated drinks also exist in the form of diet drinks, for example Diet Coke®, Pepsi®, extra. A comparative effect of the diet and regular soda carbonated drinks on the histology of the cerebellum of female albino Wistar rats was investigated. Fifteen adult female Wistar rats weighing between 180-200 g were divided into 3 groups; designated as groups A, B and C, and each group consisted of five rats. Group A was the Control group and received distilled water, while groups B and C were the experimental groups. Group B was administered 50 ml of regular soda (RS), and group C was administered 50 ml of diet soda (DS) each per day for 21 days, and the rats were sacrificed on Day 22, and their cerebellums excised and preserved. Histological result of the sections of the cerebellum showed shrunken and degenerated Purkinje cells with hypertrophied dendrites, especially in the DS group, which was less in the RS group compared to the control group. These results suggest that diet soda has adverse effect on the cerebellum of adult female albino Wistar rats.

  20. Effect of dibutyl phthalate on expression of connexin 43 and testosterone production of leydig cells in adult rats.

    PubMed

    Zhang, Jing; Jin, Shuguang; Zhao, Jinchang; Li, Huan

    2016-10-01

    To investigate the adverse effect of dibutyl phthalate (DBP) on Leydig cells and its mechanism related to gap junction, Leydig cells isolated from adult rats were treated with 0.1% dimethylsulfoxide (DMSO), 50mg/L DBP, 50mg/L DBP+10μM prostaglandin E2 (PGE2) and 40μM flutamide respectively. Radioimmunoassay, semi-quantitative RT-PCR, immunofluorescence and Western blot were applied to determine the expression of testosterone and Connexin 43 (Cx43) in Leydig cells. The expression of testosterone and Cx43 were both decreased in DBP group (P<0.05). While Cx43 was up-regulated after administered to PGE2, there was no significant change in testosterone. However, testosterone was down-regulated with a significant decrease of Cx43 in flutamide group. The results indicated that the inhibitory effect of DBP on testosterone production was not through the down-regulation of Cx43. On the contrary, the change of testosterone can influence the expression of Cx43 in Leydig cells.

  1. Effects of Asiatic Acid on Spatial Working Memory and Cell Proliferation in the Adult Rat Hippocampus

    PubMed Central

    Sirichoat, Apiwat; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanan; Leksomboon, Ratana; Chaichun, Amnart; Wigmore, Peter; Umka Welbat, Jariya

    2015-01-01

    Asiatic acid is a pentacyclic triterpene from Centella asiatica. Previous studies have reported that asiatic acid exhibits antioxidant and neuroprotective activities in cell culture. It also prevents memory deficits in animal models. The objective of this study was to investigate the relationship between spatial working memory and changes in cell proliferation within the hippocampus after administration of asiatic acid to male Spraque-Dawley rats. Control rats received vehicle (propylene glycol) while treated rats received asiatic acid (30 mg/kg) orally for 14 or 28 days. Spatial memory was determined using the novel object location (NOL) test. In animals administered asiatic acid for both 14 and 28 days, the number of Ki-67 positive cells in the subgranular zone of the dentate gyrus was significantly higher than in control animals. This was associated with a significant increase in their ability to discriminate between novel and familiar object locations in a novel object discrimination task, a hippocampus-dependent spatial memory test. Administration of asiatic acid also significantly increased doublecortin (DCX) and Notch1 protein levels in the hippocampus. These findings demonstrate that asiatic acid treatment may be a potent cognitive enhancer which improves hippocampal-dependent spatial memory, likely by increasing hippocampal neurogenesis. PMID:26445061

  2. Effects of Asiatic Acid on Spatial Working Memory and Cell Proliferation in the Adult Rat Hippocampus.

    PubMed

    Sirichoat, Apiwat; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanan; Leksomboon, Ratana; Chaichun, Amnart; Wigmore, Peter; Welbat, Jariya Umka

    2015-10-05

    Asiatic acid is a pentacyclic triterpene from Centella asiatica. Previous studies have reported that asiatic acid exhibits antioxidant and neuroprotective activities in cell culture. It also prevents memory deficits in animal models. The objective of this study was to investigate the relationship between spatial working memory and changes in cell proliferation within the hippocampus after administration of asiatic acid to male Spraque-Dawley rats. Control rats received vehicle (propylene glycol) while treated rats received asiatic acid (30 mg/kg) orally for 14 or 28 days. Spatial memory was determined using the novel object location (NOL) test. In animals administered asiatic acid for both 14 and 28 days, the number of Ki-67 positive cells in the subgranular zone of the dentate gyrus was significantly higher than in control animals. This was associated with a significant increase in their ability to discriminate between novel and familiar object locations in a novel object discrimination task, a hippocampus-dependent spatial memory test. Administration of asiatic acid also significantly increased doublecortin (DCX) and Notch1 protein levels in the hippocampus. These findings demonstrate that asiatic acid treatment may be a potent cognitive enhancer which improves hippocampal-dependent spatial memory, likely by increasing hippocampal neurogenesis.

  3. Prenatal exposure to escitalopram and/or stress in rats produces limited effects on endocrine, behavioral, or gene expression measures in adult male rats

    PubMed Central

    Bourke, Chase H.; Stowe, Zachary N.; Neigh, Gretchen N.; Olson, Darin E.; Owens, Michael J.

    2013-01-01

    Stress and/or antidepressants during pregnancy have been implicated in a wide range of long-term effects in the offspring. We investigated the long-term effects of prenatal stress and/or clinically relevant antidepressant exposure on male adult offspring in a model of the pharmacotherapy of maternal depression. Female Sprague-Dawley rats were implanted with osmotic minipumps that delivered clinically relevant exposure to the antidepressant escitalopram throughout gestation. Subsequently, pregnant females were exposed on gestational days 10–20 to a chronic unpredictable mild stress paradigm. The male offspring were analyzed in adulthood. Baseline physiological measurements were largely unaltered by prenatal manipulations. Behavioral characterization of the male offspring, with or without pre-exposure to an acute stressor, did not reveal any group differences. Prenatal stress exposure resulted in a faster return towards baseline following the peak response to an acute restraint stressor, but not an airpuff startle stressor, in adulthood. Microarray analysis of the hippocampus and hypothalamus comparing all treatment groups revealed no significantly-altered transcripts. Real time PCR of the hippocampus confirmed that several transcripts in the CRFergic, serotonergic, and neural plasticity pathways were unaffected by prenatal exposures. This stress model of maternal depression and its treatment indicate that escitalopram use and/or stress during pregnancy produced no alterations in our measures of male adult behavior or the transcriptome, however prenatal stress exposure resulted in some evidence for increased glucocorticoid negative feedback following an acute restraint stress. Study design should be carefully considered before implications for human health are ascribed to prenatal exposure to stress or antidepressant medication. PMID:23906943

  4. Effects of chronic isoproterenol administration of. beta. /sub 1/-adrenoceptors and growth of pancreas of young and adult rats

    SciTech Connect

    Schneyer, C.A.; Humphreys-Beher, M.

    1988-06-01

    (/sup 3/H)Dihydroalprenolol (DHA) binding of membranes of adult pancreas differed from that of pancreas of young rats, and the DHA binding in the presence of atenolol or butoxamine also was different in the two age groups. The adult pancreas had 93% ..beta../sub 2/- and 7% ..beta../sub 1/-adrenoceptors and did not exhibit an increased incorporation of (/sup 3/H)thymidine into deoxyribonucleic acid (DNA) following 2 days of DL-isoproterenol (ISO) administration; in contrast, pancreas of the 20-day-old rat had 71% ..beta../sub 2/-adrenoceptors and 27% ..beta../sub 1/-adrenoceptors and exhibited a 34-fold increase over that of adult, and a 6-fold increase over that of the control 20-day-old pancreas. Acinar cell differentiation was also accelerated by a 7-day regimen of ISO administration from 13 to 20 days of age. These growth responses to ISO appear to be ..beta../sub 1/ mediated. The lack of ..beta../sub 1/-adrenoceptors in the adult may account for the failure of the adult pancreas to exhibit a growth response to ISO.

  5. Effect of sub-chronic intermittent ethanol exposure on spatial learning and ethanol sensitivity in adolescent and adult rats.

    PubMed

    Swartzwelder, H S; Hogan, A; Risher, M-Louise; Swartzwelder, Rita A; Wilson, Wilkie A; Acheson, Shawn K

    2014-06-01

    It has become clear that adolescence is a period of distinct responsiveness to the acute effects of ethanol on learning and other cognitive functions. However, the effects of repeated intermittent ethanol exposure during adolescence on learning and cognition are less well studied, and other effects of repeated ethanol exposure such as withdrawal and chronic tolerance complicate such experiments. Moreover, few studies have compared the effects of repeated ethanol exposure during adolescence and adulthood, and they have yielded mixed outcomes that may be related to methodological differences and/or secondary effects of ethanol on behavioral performance. One emerging question is whether relatively brief intermittent ethanol exposure (i.e., sub-chronic exposure) during adolescence or adulthood might alter learning at a time after exposure when chronic tolerance would be expected, and whether tolerance to the cognitive effects of ethanol might influence the effect of ethanol on learning at that time. To address this, male adolescent and adult rats were pre-treated with sub-chronic daily ethanol (five doses [4.0 g/kg, i.p.] or saline at 24-h intervals, across 5 days). Two days after the last pre-exposure, spatial learning was assessed on 4 consecutive days using the Morris water maze. Half of the animals from each treatment cell received ethanol (2.0 g/kg, i.p.) 30 min prior to each testing session and half of the animals received saline. Ethanol pre-exposure altered water maze performance in adult animals but not in adolescents, and acute ethanol exposure impaired learning in animals of both ages independent of pre-exposure condition. There was no evidence of cognitive tolerance in animals of either age group. These results indicate that a relatively short period of intermittent ethanol exposure during adulthood, but not adolescence, promotes thigmotaxis in the water maze shortly after pre-exposure but does not induce cognitive tolerance to the effects of ethanol in

  6. High dietary iron concentrations enhance the formation of cholesterol oxidation products in the liver of adult rats fed salmon oil with minimal effects on antioxidant status.

    PubMed

    Brandsch, Corinna; Ringseis, Robert; Eder, Klaus

    2002-08-01

    The aim of this study was to investigate the effect of high dietary iron concentrations on the antioxidant status of rats fed two different types of fat. Four groups of male adult Sprague-Dawley rats were fed diets with adequate (50 mg iron supplemented per kg diet) or high (500 mg iron supplemented per kg diet) iron concentrations with either lard or salmon oil as dietary fat at 100 g/kg for 12 wk. The antioxidant status of the rats was profoundly influenced by the type of fat. Rats fed salmon oil diets had higher concentrations of thiobarbituric acid-reactive substances (TBARS) (P < 0.001), various cholesterol oxidation products (COP) (P < 0.001), total and oxidized glutathione (P < 0.05) and a lower concentration of alpha-tocopherol (P < 0.05) in liver and plasma than rats fed lard diets. The iron concentration of the diet did not influence the concentrations of TBARS, the activities of superoxide dismutase and glutathione peroxidase or the concentration of alpha-tocopherol in plasma or liver. The activity of catalase (P < 0.01) and the concentrations of total, oxidized and reduced glutathione (P < 0.05) in liver were slightly but significantly higher in rats fed high iron diets than in rats fed adequate iron diets, irrespective of the dietary fat. Rats fed the high iron diets with salmon oil, moreover, had higher concentrations of various COP in the liver (P < 0.001) than rats fed adequate iron diets with salmon oil. These results suggest that feeding a high iron diet does not generally affect the antioxidant status of rats but enhances the formation of COP, particularly if the diet is rich in polyunsaturated fatty acids.

  7. The effects of coprophagy in the adult rat on rate of passage of digesta and on digestibility of food fed ad libitum and in restricted amounts.

    PubMed

    Williams, V J; Senior, W

    1985-09-01

    The rate of passage of digesta and the digestibility of a nonpurified diet were studied in adult female rats prevented from coprophagy on alternate weeks by confinement to their normal feeding tunnels in metabolism cages. In food-restricted rats a decrease in the time for the first appearance in the feces of a digesta marker was noted when prevention of coprophagy was followed by permitting rats to feed on their feces while being maintained on a restricted food intake, as compared to control rats permitted coprophagy throughout. The prevention of coprophagy had no effect on the rate of passage of digesta along the small intestine. The prevention of coprophagy had no effect on the apparent digestibility of dry matter, organic matter, energy or protein when the rats were fed ad libitum. However, when rats had lost 20% or more of their body weight by restricted feeding, digestibility of the measured constituents of the food offered in restricted amounts increased, but this effect was abolished when coprophagy was prevented.

  8. Neonatal N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) treatment modifies the vulnerability to phenobarbital- and ethanol-evoked sedative-hypnotic effects in adult rats.

    PubMed

    Bortel, Aleksandra; Słomian, Lucyna; Nitka, Dariusz; Swierszcz, Michał; Jaksz, Mirella; Adamus-Sitkiewicz, Beata; Nowak, Przemysław; Jośko, Jadwiga; Kostrzewa, Richard M; Brus, Ryszard

    2008-01-01

    To study the influence of the central noradrenergic system on sensitivity to sedative-hypnotic effects mediated by the aminobutyric acid (GABA) system, intact rats were contrasted with rats in which noradrenergic nerves were largely destroyed shortly after birth with the neurotoxin DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine; 50 mg/kg sc x2, P1 and P3]. At 10 weeks, loss of the righting reflex (LORR) was used as an index to study the acute sedative-hypnotic effects of phenobarbital (100 mg/kg ip) and ethanol (4 g/kg ip, 25% v/v). Additionally, GABA concentration in the medial prefrontal cortex (PFC), hippocampus, cerebellum and brainstem was estimated by an HPLC/ED method. Neonatal DSP-4 treatment diminished the sedative-hypnotic effects of both phenobarbital and ethanol in adult rats. While the endogenous GABA content in the PFC, hippocampus, brainstem and cerebellum of DSP-4-treated rats was not altered, phenobarbital significantly decreased GABA content of both intact and DSP-4-lesioned rats by approximately 40% in the hippocampus and by approximately 20% in other brain regions at 1 h. Ethanol reduced GABA content by approximately 15-30% but only in the hippocampus and brainstem of both intact and lesioned rats. These findings indicate that the noradrenergic system exerts a prominent influence on sedative-hypnotics acting via GABAergic systems in the brain without directly altering GABA levels in the brain.

  9. Effects of Perinatal Polychlorinated Biphenyls on Adult Female Rat Reproduction: Development, Reproductive Physiology, and Second Generational Effects

    PubMed Central

    Steinberg, Rebecca M.; Walker, Deena M.; Juenger, Thomas E.; Woller, Michael J.; Gore, Andrea C.

    2009-01-01

    Perinatal exposures to endocrine-disrupting chemicals such as polychlorinated biphenyls (PCBs) can cause latent effects on reproductive function. Here, we tested whether PCBs administered during late pregnancy would compromise reproductive physiology in both the fetally-exposed female offspring (F1 generation), as well as in their female offspring (F2 generation). Pregnant Sprague-Dawley rats were treated with the PCB mixture Aroclor (A) 1221 (0, 0.1, 1 or 10 mg/kg) on embryonic days 16 and 18. Somatic and reproductive development of F1 and their F2 female offspring were monitored, including ages of eye opening, pubertal landmarks, and serum reproductive hormones. The results showed that low doses of A1221 given during this critical period of neuroendocrine development caused differential effects of A1221 on F1 and F2 female rats. In both generations, litter sex ratio was skewed towards females. In the F1 generation, additional effects were found including a significant alteration of serum luteinizing hormone (LH) in the 1 mg/kg A1221 group. The F2 generation showed more profound alterations, particularly with respect to fluctuations in hormones and reproductive tract tissues across the estrous cycle. On proestrus, the day of the preovulatory GnRH/gonadotropin surge, F2 females whose mothers had been perinatally exposed to A1221 exhibited substantially suppressed LH and progesterone concentrations, and correspondingly smaller uterine and ovarian weights on estrus, compared to F2 decendants of control rats. These latter changes suggest a dysregulation of reproductive physiology. Thus, low levels of exposure to PCBs during late fetal development cause significant consequences on the maturation and physiology of two generations of female offspring. These findings have implications for reproductive health and fertility of wildlife and humans. PMID:18305224

  10. Experience-induced fetal plasticity: the effect of gestational ethanol exposure on the behavioral and neurophysiologic olfactory response to ethanol odor in early postnatal and adult rats.

    PubMed

    Youngentob, Steven L; Kent, Paul F; Sheehe, Paul R; Molina, Juan C; Spear, Norman E; Youngentob, Lisa M

    2007-12-01

    Human fetal ethanol exposure is strongly associated with ethanol avidity during adolescence. Evidence that intrauterine olfactory experience influences chemosensory-guided postnatal behaviors suggests that an altered response to ethanol odor resulting from fetal exposure may contribute to later abuse risk. Using behavioral and neurophysiological methods, the authors tested whether ethanol exposure via the dam's diet resulted in an altered responsiveness to ethanol odor in infant and adult rats. Compared with controls, (a) fetal exposure tuned the neurophysiologic response of the olfactory epithelium to ethanol odor at some expense to its responsiveness to other odorants in infantile rats--this effect was absent in adults; (b) the neural effect in infantile rats was paralleled by an altered behavioral response to ethanol odor that was specific to this odorant--this effect was also absent in adults; and (c) a significant component of the infantile behavioral effect was attributable to ethanol's effect on the olfactory neural modality. These data provide evidence for an important relationship between prenatal ethanol experience and postnatal behavioral responsiveness to the drug that is modulated or determined by olfactory function.

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

    PubMed

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

    2005-01-01

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

  12. Effect of nano-zinc oxide on doxorubicin- induced oxidative stress and sperm disorders in adult male Wistar rats

    PubMed Central

    Badkoobeh, Puran; Parivar, Kazem; Kalantar, Seyed Mehdi; Hosseini, Seyed Davood; Salabat, Alireza

    2013-01-01

    Background: Doxorubicin (DOX), an anthracycline antibiotic, is a widely used anticancer agent. In spite of its high antitumor efficacy, the use of DOX in clinical chemotherapy is limited due to diverse toxicities, including gonadotoxicity. Objective: We investigated the protective effect of nano-zinc oxide (nZnO) as an established antioxidant on DOX-induced testicular disorders. Materials and Methods: In this experimental study 24 adult male Wistar rats were divided into four groups including one control and three experimentals (6 rats per group). They received saline (as control), DOX alone (6 mg/kg body weight, i.p.), nZnO alone (5 mg/kg body weight, i.p.), and nZnO followed by DOX. Animals were sacrificed 28 days after treatment and evaluations were made by sperm count and measuring sex hormone levels in plasma. Also total antioxidant power (TAP) and lipid peroxidation (LPO) in plasma were tested. Data was analyzed with SPSS-14 and one way ANOVA test. P<0.05 were considered to be statistically significant. Results: In the DOX-exposed rats significant differences were found compared with the control group (p=0.001) in plasma total antioxidant power (TAP) (425.50±32.33 vs. 493.33±18.54 mmol/mL), Lipid peroxidation (LPO) (3.70±0.44 vs. 2.78±0.68 μmol/mL), plasma testosterone (3.38±0.69 vs. 5.40±0.89 ng/dl), LH (0.26±0.05 vs. 0.49±0.18 mlU/mL), sperm count (157.98±6.29 vs. 171.71±4.42×106/mL) and DNA damage (11.51±3.45 vs. 6.04±2.83%). Co-administration of nZnO significantly improved DOX-induced changes (p=0.013) in plasma TAP (471.83±14.51 mmol/mL), LPO (2.83±0.75 μmol/mL), plasma testosterone (5.00±1.07 ng/dl), LH (0.52±0.08 mlU/mL), sperm count (169.13±5.01×106/mL) and DNA damage (7.00±1.67%). Conclusion: At the dose designed in the present investigation cytoprotective role of nano-zinc oxide through its antioxidant potential is illuminated in DOX-induced male gonadotoxicity. PMID:24639766

  13. Fructose rich diet-induced high plasminogen activator inhibitor-1 (PAI-1) production in the adult female rat: protective effect of progesterone.

    PubMed

    Castrogiovanni, Daniel; Alzamendi, Ana; Ongaro, Luisina; Giovambattista, Andrés; Gaillard, Rolf C; Spinedi, Eduardo

    2012-08-01

    The effect of progesterone (P4) on fructose rich diet (FRD) intake-induced metabolic, endocrine and parametrial adipose tissue (PMAT) dysfunctions was studied in the adult female rat. Sixty day-old rats were i.m. treated with oil alone (control, CT) or containing P4 (12 mg/kg). Rats ate Purina chow-diet ad libitum throughout the entire experiment and, between 100 and 120 days of age drank ad libitum tap water alone (normal diet; CT-ND and P4-ND) or containing fructose (10% w/v; CT-FRD and P4-FRD). At age 120 days, animals were subjected to a glucose tolerance test or decapitated. Plasma concentrations of various biomarkers and PMAT gene abundance were monitored. P4-ND (vs. CT-ND) rats showed elevated circulating levels of lipids. CT-FRD rats displayed high (vs. CT-ND) plasma concentrations of lipids, leptin, adiponectin and plasminogen activator inhibitor-1 (PAI-1). Lipidemia and adiponectinemia were high (vs. P4-ND) in P4-FRD rats. Although P4 failed to prevent FRD-induced hyperleptinemia, it was fully protective on FRD-enhanced plasma PAI-1 levels. PMAT leptin and adiponectin mRNAs were high in CT-FRD and P4-FRD rats. While FRD enhanced PMAT PAI-1 mRNA abundance in CT rats, this effect was absent in P4 rats. Our study supports that a preceding P4-enriched milieu prevented the enhanced prothrombotic risk induced by FRD-elicited high PAI-1 production.

  14. Effects of Ethanol on the Expression Level of Various BDNF mRNA Isoforms and Their Encoded Protein in the Hippocampus of Adult and Embryonic Rats.

    PubMed

    Shojaei, Shahla; Ghavami, Saeid; Panjehshahin, Mohammad Reza; Owji, Ali Akbar

    2015-12-21

    We aimed to compare the effects of oral ethanol (Eth) alone or combined with the phytoestrogen resveratrol (Rsv) on the expression of various brain-derived neurotrophic factor (BDNF) transcripts and the encoded protein pro-BDNF in the hippocampus of pregnant and embryonic rats. A low (0.25 g/kg body weight (BW)/day) dose of Eth produced an increase in the expression of BDNF exons I, III and IV and a decrease in that of the exon IX in embryos, but failed to affect BDNF transcript and pro-BDNF protein expression in adults. However, co-administration of Eth 0.25 g/kg·BW/day and Rsv led to increased expression of BDNF exons I, III and IV and to a small but significant increase in the level of pro-BDNF protein in maternal rats. A high (2.5 g/kg·BW/day) dose of Eth increased the expression of BDNF exons III and IV in embryos, but it decreased the expression of exon IX containing BDNF mRNAs in the maternal rats. While the high dose of Eth alone reduced the level of pro-BDNF in adults, it failed to change the levels of pro-BDNF in embryos. Eth differentially affects the expression pattern of BDNF transcripts and levels of pro-BDNF in the hippocampus of both adult and embryonic rats.

  15. Effects of Ethanol on the Expression Level of Various BDNF mRNA Isoforms and Their Encoded Protein in the Hippocampus of Adult and Embryonic Rats

    PubMed Central

    Shojaei, Shahla; Ghavami, Saeid; Panjehshahin, Mohammad Reza; Owji, Ali Akbar

    2015-01-01

    We aimed to compare the effects of oral ethanol (Eth) alone or combined with the phytoestrogen resveratrol (Rsv) on the expression of various brain-derived neurotrophic factor (BDNF) transcripts and the encoded protein pro-BDNF in the hippocampus of pregnant and embryonic rats. A low (0.25 g/kg body weight (BW)/day) dose of Eth produced an increase in the expression of BDNF exons I, III and IV and a decrease in that of the exon IX in embryos, but failed to affect BDNF transcript and pro-BDNF protein expression in adults. However, co-administration of Eth 0.25 g/kg·BW/day and Rsv led to increased expression of BDNF exons I, III and IV and to a small but significant increase in the level of pro-BDNF protein in maternal rats. A high (2.5 g/kg·BW/day) dose of Eth increased the expression of BDNF exons III and IV in embryos, but it decreased the expression of exon IX containing BDNF mRNAs in the maternal rats. While the high dose of Eth alone reduced the level of pro-BDNF in adults, it failed to change the levels of pro-BDNF in embryos. Eth differentially affects the expression pattern of BDNF transcripts and levels of pro-BDNF in the hippocampus of both adult and embryonic rats. PMID:26703578

  16. Toxic effects of cadmium on GABA and taurine content in different brain areas of adult male rats.

    PubMed

    Lafuente, A; González-Carracedo, A; Cabaleiro, T; Romero, A; Esquifino, A I

    2005-09-01

    This work assesses the possible changes in gamma amino butyric acid (GABA) and taurine content in the hypothalamus, the median eminence and striatum after the exposure to various doses of cadmium. Cadmium chloride (CdCl2) was administered in the drinking water at the doses of 5, 10, 25, 50 or 100 ppm to adult male rats for 1 month. In the anterior hypothalamus, taurine and GABA content decreased with the dose of 10 ppm of CdCl2 only. Cadmium exposure decreased both GABA and taurine content in mediobasal hypothalamus except for the 50 ppm dose. In posterior hypothalamus GABA and taurine content was not affected by cadmium treatment. As far as the median eminence, 5 or 10 ppm of CdCl2 increased taurine concentration, and at a dose of 5 ppm enhanced GABA content. A significant decrease of GABA and taurine concentration was seen in the striatum at any dose of cadmium used. The concentration of cadmium increased in the hypothalamus and in the striatum in animals receiving CdCl2 in the drinking water at doses of 25, 50 or 100 ppm. The results indicate that cadmium globally decreased GABA and taurine content in the brain areas studied through effects that were not dose dependent.

  17. Antioxidant effect of vitamin E and selenium on hepatotoxicity induced by dimethoate in female adult rats.

    PubMed

    Ben Amara, Ibtissem; Soudani, Nejla; Troudi, Afef; Bouaziz, Hanen; Boudawara, Tahia; Zeghal, Najiba

    2011-05-01

    Acute exposure to pesticides can cause hepatotoxicity. Our study pertains to the potential ability of selenium and/or vitamin E, used as nutritional supplements, to alleviate oxidative stress induced by dimethoate. Female Wistar rats were randomly divided into seven groups of six each: group I served as controls; group II received in their drinking water dimethoate (2 g L(-1)); group III received both dimethoate and selenium (0.5 mg/kg of diet); group IV was treated with dimethoate and vitamin E (100 mg/kg of diet); group V received dimethoate+selenium+vitamin E and groups VI and VII received either selenium or vitamin E. The exposure of rats to dimethoate for 30 days promoted oxidative stress with an increase in malondialdehyde and a decrease in glutathione and non-protein thiol levels. A decrease in glutathione peroxidase, superoxide dismutase and catalase activities was also observed. While, plasma transaminases, lactate dehydrogenase activities and bilirubin levels increased. Co-administration of selenium and/or vitamin E through diet improved the biochemical parameters cited above. Liver histological studies confirmed biochemical parameters and the beneficial roles of selenium and vitamin E.

  18. The effect of neonatal maternal stress on plasma levels of adrenocorticotropic hormone, corticosterone, leptin, and ghrelin in adult male rats exposed to acute heterotypic stressor.

    PubMed

    Holubová, A; Štofková, A; Jurčovičová, J; Šlamberová, R

    2016-12-22

    Activation of the hypothalamic-pituitary-adrenal (HPA) axis is important for maintenance of homeostasis during stress. Recent studies have shown a connection between the HPA axis and adipose tissue. The present study investigated the effect of acute heterotypic stress on plasma levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), leptin, and ghrelin in adult male rats with respect to neonatal maternal social and physical stressors. Thirty rat mothers and sixty of their male progeny were used. Pups were divided into three groups: unstressed control (C), stressed by maternal social stressor (S), stressed by maternal social and physical stressors (SW). Levels of hormones were measured in adult male progeny following an acute swimming stress (10 min) or no stress. ELISA immunoassay was used to measured hormones. The ACTH and CORT levels were significantly increased in all groups of adult progeny after acute stress; however, CORT levels were significantly lower in both neonatally stressed groups compared to controls. After acute stress, plasma leptin levels were decreased in the C and SW groups but increased in the S group. The data suggest that long-term neonatal stressors lead to lower sensitivity of ACTH receptors in the adrenal cortex, which could be a sign of stress adaptation in adulthood. Acute stress in adult male rats changes plasma levels of leptin differently relative to social or physical neonatal stressors.

  19. Protective effect of curcumin against experimentally induced aflatoxicosis on the renal cortex of adult male albino rats: a histological and immunohisochemical study

    PubMed Central

    El-Mahalaway, Abeer M

    2015-01-01

    Background: Aflatoxin contamination of foods is a worldwide problem. Chronic aflatoxin exposure is associated with kidney damage. Curcumin is a herbal agent, used in medicine with a wide range of beneficial therapeutic effects. Objective: to evaluate the effect of curcumin against experimentally induced aflatoxicosis on the renal cortex of adult male albino rats. Materials and methods: Forty adult male rats were included and they were divided equally into 4 groups (10 rats each): Group I (control group), group II (Curcumin group): The rats received curcumin (200 mg/kg b.w.) orally by gastric tube for 5 days/week, group III (Aflatoxin B1 group): The rats received aflatoxin B1 (250 μg/kg b.w./day) orally by gastric tube 5 days/week for 4 weeks, group IV (Aflatoxin B1 and Curcumin group): The rats received aflatoxin and curcumin orally by gastric tube 5 days/week for 4 weeks. Kidney specimens were prepared and sections were stained with hematoxylin and eosin, Masson’s trichrome, Periodic acid Schiff, immunohistochemical detection of desmin and Bcl2. Results: The tubules of group III showed degenerative and necrotic changes with disruption of basal lamina. There was a significant decrease Bcl2 expression in the tubules, but the glomeruli showed an enlargement with dilation of their capillaries lumina in some areas, while the other areas showed glomerular atrophy with obliteration of their capillaries lumina. There was a significant increase in desmin expression in the glomerular cells. The interstitium showed hemorrhage and cellular infiltration. Group IV showed improvement of the histological and immunohistochemical changes described before. Conclusion: Aflatoxin B1 has deleterious effects of on the histological structure of the rat’s renal cortex and curcumin minimized these effects as it has antioxidant, anti-inflammatory and antiapoptotic activities. We advise eating nutritious diets that contain sufficient amounts of curcumin and regulation must implement to

  20. Effect of hypothalamic electrical stimulation on protein synthesis in organs of adult and old rats

    SciTech Connect

    Frol'kis, V.V.; Muradyan, K.K.; Rushkevich, Yu.E.; Mozzhukhina, T.G.; Khilobok, I.Yu.; Gol'dshtein, N.B.

    1986-12-01

    Age differences in hypothalamic regulation of total protein synthesis in different organs and also of liver chromatin proteins were compared in this investigation. Rats were used in the experiments and the intensity of protein synthesis was judged from the relative specific radioactivity which was determined as the ratio of the specific radioactivities of acid-insoluble and acid-soluble materials, separated by means of nitrocellulose membrane filters. Protein was determined by two-wave spectrophotometry and the radioactivity of all samples was measured on a Mark III radio spectrometer. The investigations showed that hypothalmic electrical stimulation causes a marked increase in /sup 3/H-leucine incorporation into protein of active and inactive liver chromatin.

  1. Spaceflight effects on adult rat muscle protein, nucleic acids, and amino acids

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1986-01-01

    Exposure to conditions of weightlessness has been associated with decrements in muscle mass and strength. The present studies were undertaken to determine muscle responses at the cellular level. Male Sprague-Dawley rats (360-410 g) were exposed to 7 days of weightlessness during the Spacelab-3 shuttle flight (May 1985). Animals were killed 12 h postflight, and soleus (S), gastrocnemius (G), and extensor digitorum longus (EDL) muscles were excised. Muscle protein, RNA, and DNA were extracted and quantified. Differential muscle atrophy was accompanied by a significant (P less than 0.05) reduction in total protein only in S muscles. There were no significant changes in protein concentration (mg/g) in the muscles examined. In S muscles from flight animals, sarcoplasmic protein accounted for a significantly greater proportion of total protein that in ground controls (37.5 vs. 32.5%). Tissue concentrations (nmol/g) of asparagine-aspartate, glutamine-glutamate, glycine, histidine, and lysine were significantly reduced (from 17 to 63%) in S muscles from flight animals, but only glutamine-glutamate levels were decreased in the G and EDL. Muscle DNA content (microgram) was unchanged in the tissues examined, but S muscle DNA concentration (micrograms/mg) increased 27%. RNA content (micrograms) was significantly (P less than 0.025) reduced in S (-28%) and G(-22%) muscles following spaceflight. These results identify specific alterations in rat skeletal muscle during short term (7-day) exposure to weightlessness and compare favorably with observations previously obtained from ground-based suspension simulations.

  2. Effects of testicular transfixation on seminiferous tubule morphology and sperm parameters of prepubertal, pubertal, and adult rats.

    PubMed

    Ribeiro, Carina T; De Souza, Diogo B; Costa, Waldemar S; Pereira-Sampaio, Marco A; Sampaio, Francisco J B

    2015-10-15

    Orchiopexy is performed as part of cryptorchidism and testicular torsion treatment. The inflammation caused by the needle and suture penetration has been suggested to be one of the possible causes of subfertility after parenchymal transfixation of the testicles. The purpose of the present study was to investigate testicular alterations after parenchymal transfixation sutures at different ages in rats. Prepubertal, pubertal, and adult rats were submitted to parenchymal suturing (without tying the knots, thus avoiding local ischemic injury) of the right testicle, which was maintained for 4 hours. All animals were subjected to euthanasia on completion of 14 weeks of life. The right testicles were studied as the sutured testicles, whereas the left organs were studied as contralateral. One age-matched control group of rats that was not submitted to any procedure was used for comparison. During euthanasia, sperm were collected from the tail of the epididymal and evaluated for concentration, motility, and viability. Samples from testicular tissue were collected for morphologic analysis. Sperm analysis indicated that only the adult operated animals presented reductions in motility (38.2% of adult vs. 54.1% of control; P = 0.02) and viability (16.6% of adult vs. 24.6% of control; P = 0.003). Several morphologic alterations were noted both in sutured and in contralateral testes at all ages. For instance, the seminiferous epithelium volumetric density of right testicles was reduced from 50.4% in controls to 32.3% in prepubertal operated animals, 45.3% in pubertal operated animals, and 39.4% in adult operated animals (P < 0.05). The seminiferous epithelium volumetric density was also reduced to 39.9% and 39.0% in contralateral testicles of animals operated before and after puberty, respectively (P < 0.05). The animals operated on before puberty and in adulthood showed more testicular morphologic alterations, as seminiferous tubule volumetric density, seminiferous tubule length

  3. A comparison of the apoptotic effect of Delta(9)-tetrahydrocannabinol in the neonatal and adult rat cerebral cortex.

    PubMed

    Downer, Eric J; Gowran, Aoife; Campbell, Veronica A

    2007-10-17

    The maternal use of cannabis during pregnancy results in a number of cognitive deficits in the offspring that persist into adulthood. The endocannabinoid system has a role to play in neurodevelopmental processes such as neurogenesis, migration and synaptogenesis. However, exposure to phytocannabinoids, such as Delta(9)-tetrahydrocannabinol, during gestation may interfere with these events to cause abnormal patterns of neuronal wiring and subsequent cognitive impairments. Aberrant cell death evoked by Delta(9)-tetrahydrocannabinol may also contribute to cognitive deficits and in cultured neurones Delta(9)-tetrahydrocannabinol induces apoptosis via the CB(1) cannabinoid receptor. In this study we report that Delta(9)-tetrahydrocannabinol (5-50 microM) activates the stress-activated protein kinase, c-jun N-terminal kinase, and the pro-apoptotic protease, caspase-3, in in vitro cerebral cortical slices obtained from the neonatal rat brain. The proclivity of Delta(9)-tetrahydrocannabinol to impact on these pro-apoptotic signalling molecules was not observed in in vitro cortical slices obtained from the adult rat brain. In vivo, subcutaneous administration of Delta(9)-tetrahydrocannabinol (1-30 mg/kg) activated c-jun N-terminal kinase, caspase-3 and cathepsin-D, and induced DNA fragmentation in the cerebral cortex of neonatal rats. In contrast, in vivo administration of Delta(9)-tetrahydrocannabinol to adult rats was not associated with the apoptotic pathway in the cerebral cortex. The data provide evidence which supports the hypothesis that the neonatal rat brain is more vulnerable to the neurotoxic influence of Delta(9)-tetrahydrocannabinol, suggesting that the cognitive deficits that are observed in humans exposed to marijuana during gestation may be due, in part, to abnormal engagement of the apoptotic cascade during brain development.

  4. Neuroprotective effects of N-acetyl-cysteine and acetyl-L-carnitine after spinal cord injury in adult rats.

    PubMed

    Karalija, Amar; Novikova, Liudmila N; Kingham, Paul J; Wiberg, Mikael; Novikov, Lev N

    2012-01-01

    Following the initial acute stage of spinal cord injury, a cascade of cellular and inflammatory responses will lead to progressive secondary damage of the nerve tissue surrounding the primary injury site. The degeneration is manifested by loss of neurons and glial cells, demyelination and cyst formation. Injury to the mammalian spinal cord results in nearly complete failure of the severed axons to regenerate. We have previously demonstrated that the antioxidants N-acetyl-cysteine (NAC) and acetyl-L-carnitine (ALC) can attenuate retrograde neuronal degeneration after peripheral nerve and ventral root injury. The present study evaluates the effects of NAC and ALC on neuronal survival, axonal sprouting and glial cell reactions after spinal cord injury in adult rats. Tibial motoneurons in the spinal cord were pre-labeled with fluorescent tracer Fast Blue one week before lumbar L5 hemisection. Continuous intrathecal infusion of NAC (2.4 mg/day) or ALC (0.9 mg/day) was initiated immediately after spinal injury using Alzet 2002 osmotic minipumps. Neuroprotective effects of treatment were assessed by counting surviving motoneurons and by using quantitative immunohistochemistry and Western blotting for neuronal and glial cell markers 4 weeks after hemisection. Spinal cord injury induced significant loss of tibial motoneurons in L4-L6 segments. Neuronal degeneration was associated with decreased immunostaining for microtubular-associated protein-2 (MAP2) in dendritic branches, synaptophysin in presynaptic boutons and neurofilaments in nerve fibers. Immunostaining for the astroglial marker GFAP and microglial marker OX42 was increased. Treatment with NAC and ALC rescued approximately half of the motoneurons destined to die. In addition, antioxidants restored MAP2 and synaptophysin immunoreactivity. However, the perineuronal synaptophysin labeling was not recovered. Although both treatments promoted axonal sprouting, there was no effect on reactive astrocytes. In contrast, the

  5. Protective effect of pumpkin seed extract on sperm characteristics, biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide.

    PubMed

    Aghaei, S; Nikzad, H; Taghizadeh, M; Tameh, A A; Taherian, A; Moravveji, A

    2014-10-01

    Cancer treatment with cyclophosphamide (CP) may result in reproductive toxicity as one of its side effects. The pumpkin seed is a rich natural source of antioxidant. We have assessed the possible protective efficacy of pumpkin seed extract on sperm characteristics, biochemical parameters and epididymal histology of CP-treated rats. Male adult Wistar rats were categorised into four groups. Group 1 served as control and received intraperitoneal (IP) injection of isotonic saline solution. Group 2 rats were treated with CP by IP injection in a single dose of 100 mg/kg body weight, only once. Group 3 and 4 received CP plus 300 and 600 mg/kg pumpkin seed extract respectively. Six weeks after treatment, sperm characteristics, biochemical parameters and histopathological changes were examined. Results showed that, sperm characteristics in CP-treated rats were significantly decreased. Biochemical analysis results showed that the co-administration of 300 mg pumpkin seed extract could increase the total antioxidant capacity (TAC) level significantly. In CP-treated rats, histopathological changes such as vacuolisation, disorganisation and separation of epididymal epithelium were observed as well. Interestingly, pumpkin seed extract could improve the above-mentioned parameters remarkably in CP-treated rats. Our findings indicated that pumpkin seed extract might be used as protective agent against CP-induced reproductive toxicity. © 2013 Blackwell Verlag GmbH.

  6. Evaluation of the effects of electrical stimulation on cartilage repair in adult male rats.

    PubMed

    Zuzzi, Denise Cristina; Ciccone, Carla de Campos; Neves, Lia Mara Grosso; Mendonça, Josué Sampaio; Joazeiro, Paulo Pinto; Esquisatto, Marcelo Augusto Marretto

    2013-08-01

    This study describes the organization of mature hyaline xiphoid cartilage during repair in animals submitted to electrical current stimulation. Twenty male Wistar rats, 90 days old, were divided into a control group (CG) and a treated group (TG). A cylindrical full-thickness cartilage defects were created with a 3-mm punch in anesthetized animals. After 24h, TG received daily applications of a continuous electrical current (1Hz/20μA) for 5min. The animals were sacrificed after 7, 21 and 35 days for structural analysis. In CG, the repair tissue presented fibrous characteristics, with fibroblastic cells being infiltrated and permeated by blood vessels. Basophilic foci of cartilage tissue were observed on day 35. In TG, the repair tissue also presented fibrous characteristics, but a larger number of thick collagen fibers were seen on day 21. A large number of cartilaginous nests were observed on day 35. Cell numbers were significantly higher in TG. Calcification points were detected in TG on day 35. There was no difference in elastic fibers between groups. Ultrastructural analysis revealed the presence of chondrocyte-like cells in CG at all time points, but only on days 21 and 35 in TG. The amount of cuprolinic blue-stained proteoglycans was higher in TG on day 35. Microcurrent stimulation accelerates the repair process in non-articular hyaline cartilage.

  7. Effects of dietary phenochlor DP5 on microsomal enzymes, liver, and blood lipids in adult male and female rats after subchronic and perinatal exposures

    SciTech Connect

    Poul, J.M.

    1987-08-01

    PCBs have numerous toxic effects on laboratory animals, namely hepatotoxicity, immunotoxicity, reproductive and hormonal effects, mutagenic and carcinogenic potency (Safe 1984). They have been recognized as potent inducers of many microsomal drug metabolizing enzymes in several species. Moreover, treatment of rats with PCBs gave rise to altered lipid metabolism with accumulation of lipids in the liver. In most of these studies male rats have been used. However, sex differences in the effects of xenobiotics on microsomal drug metabolizing enzymes have been shown particularly with PCBs and little was known about differences in the effects of PCBs on lipid metabolism. This study was designed to investigate the effects of a subchronic treatment with Phenochlor DP5 on some microsomal drug metabolizing enzyme activities and on liver and blood lipids of male and female rats. The long-term effects of DP5 administration during pre and postnatal period on adult microsomal enzyme activities and liver and blood lipids of both sexes have also been studied. A possible xenobiotic imprinting of the hepatic monooxygenase system during neonatal period has been shown recently, and it has been recognized that some functional defects which often manifest themselves in adult period may be induced prenatally or before weaning.

  8. Nonspecific effects of the gap junction blocker mefloquine on fast hippocampal network oscillations in the adult rat in vitro.

    PubMed

    Behrens, C J; Ul Haq, R; Liotta, A; Anderson, M L; Heinemann, U

    2011-09-29

    It has been suggested that gap junctions are involved in the synchronization during high frequency oscillations as observed during sharp wave-ripple complexes (SPW-Rs) and during recurrent epileptiform discharges (REDs). Ripple oscillations during SPW-Rs, possibly involved in memory replay and memory consolidation, reach frequencies of up to 200 Hz while ripple oscillations during REDs display frequencies up to 500 Hz. These fast oscillations may be synchronized by intercellular interactions through gap junctions. In area CA3, connexin 36 (Cx36) proteins are present and potentially sensitive to mefloquine. Here, we used hippocampal slices of adult rats to investigate the effects of mefloquine, which blocks Cx36, Cx43 and Cx50 gap junctions on both SPW-Rs and REDs. SPW-Rs were induced by high frequency stimulation in the CA3 region while REDs were recorded in the presence of the GABA(A) receptor blocker bicuculline (5 μM). Both, SPW-Rs and REDs were blocked by the gap junction blocker carbenoxolone. Mefloquine (50 μM), which did not affect stimulus-induced responses in area CA3, neither changed SPW-Rs nor superimposed ripple oscillations. During REDs, 25 and 50 μM mefloquine exerted only minor effects on the expression of REDs but significantly reduced the amplitude of superimposed ripples by ∼17 and ∼54%, respectively. Intracellular recordings of CA3 pyramidal cells revealed that mefloquine did not change their resting membrane potential and input resistance but significantly increased the afterhyperpolarization following evoked action potentials (APs) resulting in reduced probability of AP firing during depolarizing current injection. Similarly, mefloquine caused a reduction in AP generation during REDs. Together, our data suggest that mefloquine depressed RED-related ripple oscillations by reducing high frequency discharges and not necessarily by blocking electrical coupling.

  9. Sex-dependent effects of early life inflammatory pain on sucrose intake and sucrose-associated hippocampal Arc expression in adult rats.

    PubMed

    Henderson, Yoko O; Nalloor, Rebecca; Vazdarjanova, Almira; Murphy, Anne Z; Parent, Marise B

    2017-05-01

    We hypothesize that dorsal hippocampal (dHC) neurons, which are critical for episodic memory, form a memory of a meal and inhibit the initiation of the next meal and the amount ingested during that meal. In support, we showed previously that (1) consuming a sucrose meal induces expression of the synaptic plasticity marker activity-regulated cytoskeleton-associated protein (Arc) in dHC neurons and (2) reversible inactivation of these neurons immediately following a sucrose meal accelerates the onset of the next meal and increases the size of that meal. These data suggest that hippocampal-dependent memory inhibits intake; therefore, the following experiments were conducted to determine whether hippocampal-dependent memory impairments are associated with increased intake. We reported recently that one episode of early life inflammatory pain impairs dHC-dependent memory in adult rats. The present study determined whether neonatal inflammatory pain also increases sucrose intake and attenuates sucrose-associated Arc expression. Male and female Sprague-Dawley rats were given an intraplantar injection of the inflammatory agent carrageenan (1%) on the day of birth and sucrose intake and sucrose-associated dHC Arc expression were measured in adulthood. Neonatal inflammatory pain increased sucrose intake in adult female and male rats, decreased sucrose-associated dHC Arc expression in female rats, and tended to have a similar effect on Arc expression in male rats. Neonatal inflammatory pain significantly decreased the interval between two sucrose meals in female but not in male rats. Morphine administration at the time of insult attenuated the effects of injury on sucrose intake. Collectively, these findings indicate that one brief episode of inflammatory pain on the day of birth has a long long-lasting, sex-dependent impact on intake of a palatable food in adulthood. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Adolescent and Adult Rats Differ in the Amnesic Effects of Acute Ethanol in Two Hippocampus-Dependent Tasks: Trace and Contextual Fear Conditioning

    PubMed Central

    Hunt, Pamela S.; Barnet, Robert C.

    2015-01-01

    Experience-produced deficits in trace conditioning and context conditioning have been useful tools for examining the role of the hippocampus in learning. It has also been suggested that learning in these tasks is especially vulnerable to neurotoxic effects of alcohol during key developmental periods such as adolescence. In five experiments we systematically examined the presence and source of age-dependent vulnerability to the memory-disrupting effects of acute ethanol in trace conditioning and contextual fear conditioning. In Experiment 1a pre-training ethanol disrupted trace conditioning more strongly in adolescent (postnatal day, PD30-35) than adult rats (PD65-75). In Experiment 1b when pre-training ethanol was accompanied by pre-test ethanol no deficit in trace conditioning was observed in adolescents, suggesting that state-dependent retrieval failure mediated ethanol's disruption of trace conditioning at this age. Experiments 2a and 2b examined the effect of ethanol pretreatment on context conditioning. Here, adult but not adolescent rats were impaired in conditioned freezing to context cues. Experiment 2c explored state-dependency of this effect. Pre-training ethanol continued to disrupt context conditioning in adults even when ethanol was also administered prior to test. Collectively these findings reveal clear age-dependent and task-dependent vulnerabilities in ethanol's disruptive effects on hippocampus-dependent memory. Adolescents were more disrupted by ethanol in trace conditioning than adults, and adults were more disrupted by ethanol in context conditioning than adolescents. We suggest that adolescents may be more susceptible to changes in internal state (state-dependent retrieval failure) than adults and that ethanol disrupted performance in trace and context conditioning through different mechanisms. Relevance of these findings to theories of hippocampus function is discussed. PMID:26192910

  11. Adolescent and adult rats differ in the amnesic effects of acute ethanol in two hippocampus-dependent tasks: Trace and contextual fear conditioning.

    PubMed

    Hunt, Pamela S; Barnet, Robert C

    2016-02-01

    Experience-produced deficits in trace conditioning and context conditioning have been useful tools for examining the role of the hippocampus in learning. It has also been suggested that learning in these tasks is especially vulnerable to neurotoxic effects of alcohol during key developmental periods such as adolescence. In five experiments we systematically examined the presence and source of age-dependent vulnerability to the memory-disrupting effects of acute ethanol in trace conditioning and contextual fear conditioning. In Experiment 1a pre-training ethanol disrupted trace conditioning more strongly in adolescent (postnatal day, PD30-35) than adult rats (PD65-75). In Experiment 1b when pre-training ethanol was accompanied by pre-test ethanol no deficit in trace conditioning was observed in adolescents, suggesting that state-dependent retrieval failure mediated ethanol's disruption of trace conditioning at this age. Experiment 2a and b examined the effect of ethanol pretreatment on context conditioning. Here, adult but not adolescent rats were impaired in conditioned freezing to context cues. Experiment 2c explored state-dependency of this effect. Pre-training ethanol continued to disrupt context conditioning in adults even when ethanol was also administered prior to test. Collectively these findings reveal clear age-dependent and task-dependent vulnerabilities in ethanol's disruptive effects on hippocampus-dependent memory. Adolescents were more disrupted by ethanol in trace conditioning than adults, and adults were more disrupted by ethanol in context conditioning than adolescents. We suggest that adolescents may be more susceptible to changes in internal state (state-dependent retrieval failure) than adults and that ethanol disrupted performance in trace and context conditioning through different mechanisms. Relevance of these findings to theories of hippocampus function is discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Effect of nutritional recovery with soybean flour diet on body composition, energy balance and serum leptin concentration in adult rats

    PubMed Central

    Cheim, Loanda Maria G; Oliveira, Elisângela A; Arantes, Vanessa C; Veloso, Roberto V; Reis, Marise Auxiliadora B; Gomes-da-Silva, Maria Helena G; Carneiro, Everardo M; Boschero, Antonio C; Latorraca, Márcia Q

    2009-01-01

    Background Malnutrition in early life is associated with obesity in adulthood and soybean products may have a beneficial effect on its prevention and treatment. This study evaluated body composition, serum leptin and energy balance in adult rats subjected to protein restriction during the intrauterine stage and lactation and recovering on a soybean flour diet. Methods Five groups of the Wistar strain of albino rats were used: CC, offspring born to and suckled by mothers fed a control diet and fed the same diet after weaning; CS, offspring born to and suckled by mothers fed a control diet and fed a soybean diet with 17% protein after weaning; LL, offspring of mothers fed a low protein diet and fed the same diet after weaning; LC, offspring of mothers fed a low protein diet, but fed a control diet after weaning; LS, offspring of mothers fed a low protein diet, but fed a soybean diet with 17% protein after weaning. Food intake, body, perirenal and retroperitoneal adipose tissue were measured in grams. Leptin was quantified using the Enzyme Linked Immuno Sorbent Assay (ELISA) and insulin by radioimmunoassay (RIA). Carcass composition was determined by chemical methods and energy expenditure was calculated by the difference between energy intake and carcass energy gain. Data were tested by analysis of variance (ANOVA). Results The LC and LS groups had higher energetic intake concerning body weight, lower energy expenditure, proportion of fat carcass and fat pads than CC and CS groups. The LS group showed reduced body weight gain and lower energy efficiency, which was reflected in less energy gain as protein and the proportion of carcass protein, and lower energy gain as lipid than in the LC groups, although both groups had eaten the same amount of diet and showed equal energy expenditure. Serum leptin did not differ among groups and was unrelated to food or energy intake and energy expenditure. Serum insulin was higher in the LS than in the LC group. Conclusion Protein

  13. Interactive effects of chronic stress and a high-sucrose diet on nonalcoholic fatty liver in young adult male rats.

    PubMed

    Corona-Pérez, Adriana; Díaz-Muñoz, Mauricio; Cuevas-Romero, Estela; Luna-Moreno, Dalia; Valente-Godínez, Héctor; Vázquez-Martínez, Olivia; Martínez-Gómez, Margarita; Rodríguez-Antolín, Jorge; Nicolás-Toledo, Leticia

    2017-10-02

    Glucocorticoids have been implicated in nonalcoholic fatty liver diseases (NAFLD). The influence of a palatable diet on the response to stress is controversial. This study explored whether a high-sucrose diet could protect from hepatic steatosis induced by chronic restraint stress in young adult rats. Male Wistar rats aged 21 days were allocated into four groups (n = 6-8 per group): control, chronic restraint stress, 30% sucrose diet, and 30% sucrose diet plus chronic restraint stress. After being exposed to either tap water or sucrose solution during eight weeks, half of the rats belonging to each group were subject or not to repeated restraint stress (1 h per day, 5 days per week) during four weeks. Triacylglycerol (TAG), oxidative stress, activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1), infiltration of immune cells, and glycogen amount in the liver were quantified. Serum concentrations of corticosterone and testosterone were also measured. The stressed group showed normal serum concentrations of corticosterone and did not have hepatic steatosis. However, this group showed increased glycogen, inflammation, mild fibrosis, oxidative stress, and a high activity of 11β-HSD-1 in the liver. The group exposed to the high-sucrose diet had lower concentrations of corticosterone, hepatic steatosis and moderate fibrosis. The group subject to high-sucrose diet plus chronic restraint stress showed low concentrations of corticosterone, hepatic steatosis, oxidative stress, and high concentrations of testosterone. Thus, restraint stress and a high-sucrose diet each generate different components of nonalcoholic fatty liver in young adult rats. The combination of both the factors could promote a faster development of NAFLD.

  14. Effects of sex and housing on social, spatial, and motor behavior in adult rats exposed to moderate levels of alcohol during prenatal development.

    PubMed

    Rodriguez, Carlos I; Magcalas, Christy M; Barto, Daniel; Fink, Brandi C; Rice, James P; Bird, Clark W; Davies, Suzy; Pentkowski, Nathan S; Savage, Daniel D; Hamilton, Derek A

    2016-10-15

    Persistent deficits in social behavior, motor behavior, and behavioral flexibility are among the major negative consequences associated with exposure to ethanol during prenatal development. Prior work from our laboratory has linked moderate prenatal alcohol exposure (PAE) in the rat to deficits in these behavioral domains, which depend upon the ventrolateral frontal cortex (Hamilton et al., 2014) [20]. Manipulations of the social environment cause modifications of dendritic morphology and experience-dependent immediate early gene expression in ventrolateral frontal cortex (Hamilton et al., 2010) [19], and may yield positive behavioral outcomes following PAE. In the present study we evaluated the effects of housing PAE rats with non-exposed control rats on adult behavior. Rats of both sexes were either paired with a partner from the same prenatal treatment condition (ethanol or saccharin) or from the opposite condition (mixed housing condition). At four months of age (∼3 months after the housing manipulation commenced), social behavior, tongue protrusion, and behavioral flexibility in the Morris water task were measured as in (Hamilton et al., 2014) [20]. The behavioral effects of moderate PAE were primarily limited to males and were not ameliorated by housing with a non-ethanol exposed partner. Unexpectedly, social behavior, motor behavior, and spatial flexibility were adversely affected in control rats housed with a PAE rat (i.e., in mixed housing), indicating that housing with a PAE rat has broad behavioral consequences beyond the social domain. These observations provide further evidence that moderate PAE negatively affects social behavior, and underscore the importance of considering potential negative effects of housing with PAE animals on the behavior of critical comparison groups.

  15. The effect of interburst intervals on measures of hippocampal LTP in the freely moving adult male rat.

    PubMed

    Fortin, D A; Bronzino, J D

    2001-08-01

    An important factor in the induction and maintenance of long-term potentiation (LTP) is the tetanization paradigm. This paper presents the changes associated with the induction and maintenance of hippocampal LTP in the freely moving adult male rat, subjected to three different tetanization paradigms. These results indicate that specific LTP measures including (1) synaptic activation, as measured by the slope of the dentate granule cell population excitatory postsynaptic potential, and (2) cellular response, as measured by the dentate population spike amplitude, evoked by single-pulse stimulation of the medial perforant pathway are dependent on the interburst interval of the bursting paradigm commonly used in LTP studies.

  16. Effects of ethanol exposure on subsequent acquisition and extinction of ethanol self-administration and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats: II. Adult exposure.

    PubMed

    Rodd-Henricks, Zachary A; Bell, Richard L; Kuc, Kelly A; Murphy, James M; McBride, William J; Lumeng, Lawrence; Li, Ting-Kai

    2002-11-01

    In a preceding study, we reported that ethanol (EtOH) consumption during periadolescence in alcohol-preferring (P) rats produced significant effects on the acquisition, extinction, Pavlovian spontaneous recovery (PSR), and reacquisition of operant self-administration of EtOH. The objective of the present study was to determine if EtOH consumption during adulthood produced similar effects on subsequent operant behaviors. Adult female P rats (>135 days of age) were given 24 hr free-choice access to 15% EtOH for 30 days or were similarly housed and received water only. After a 15 day period of no EtOH access and without any prior training, adult alcohol drinking and adult alcohol-naïve rats were placed in standard two-lever (15% EtOH and water) chambers to examine acquisition of EtOH self-administration. After stable responding was established on a concurrent fixed ratio (FR) 5 FR1 schedule for EtOH versus water, the P rats underwent extinction training for nine sessions. After extinction and a 2 week home cage period (with no operant sessions or access to EtOH), rats were returned to the operant chambers in the absence of reward for seven consecutive sessions to test for PSR. After PSR testing, animals were maintained in their home cage for a week, before being reintroduced to the operant chambers and allowed to respond for EtOH and water. Both the adult alcohol-drinking and adult alcohol-naïve groups rapidly acquired EtOH self-administration, expressed a pronounced PSR, which was augmented by EtOH priming and the presence of a discriminative stimulus (odor cue), and increased responding when EtOH was reinstated. Adult pre-exposure to EtOH did not alter any of the operant measures. The results of this study suggest that, unlike the results with EtOH pre-exposure during periadolescence, chronic alcohol drinking by P rats in adulthood did not produce sufficient long-lasting changes in neuronal function to alter subsequent operant acquisition of alcohol self

  17. [Effect of fetal adrenal hormones on the reactivity of the hypothalamo-hypophyseal-adrenocortical system in the adult rat].

    PubMed

    Dygalo, N N; Naumenko, E V

    1984-01-01

    It was found in the experiments on adult males, descendants of the intact or adrenalectomized (prior to mating) female rats which were injected during the pregnancy with adrenaline, hydrocortisone or saline solution, that the reaction of their hypophysial-adrenocortical system to emotional stress or injection of noradrenaline into brain were inversely proportional to the content of corticosteroids, rather than of adrenaline, in the blood of their mothers during the pregnancy. On the other hand, the coupled changes of the levels of corticosteroids and adrenaline in the blood of pregnant mothers only was accompanied by the marked decrease in the sensitivity of brain cholinergic mechanisms in descendants. Hence, the changes of the levels of both adrenaline and corticosterids in the blood of pregnant females modify the reactivity of hypophysial-adrenocortical system of adult descendants, apparently, via the development of brain neurochemical mechanisms in the foetuses. But the role of these hormones is different.

  18. THE EFFECTS OF ETHINYL ESTRADIOL ON SPERMATOGENESIS IN THE ADULT MALE RAT

    EPA Science Inventory

    Recently, increases in male infertility have been attributed to exposure to environmental estrogens. Decreased sperm concentrations and increased infertility have been reported in the human, while many reports have documented reproductive effects due to estrogenic exposure in ani...

  19. THE EFFECTS OF ETHINYL ESTRADIOL ON SPERMATOGENESIS IN THE ADULT MALE RAT

    EPA Science Inventory

    Recently, increases in male infertility have been attributed to exposure to environmental estrogens. Decreased sperm concentrations and increased infertility have been reported in the human, while many reports have documented reproductive effects due to estrogenic exposure in ani...

  20. Effect of prenatal stress on memory, nicotine withdrawal and 5HT1A expression in raphe nuclei of adult rats.

    PubMed

    Said, N; Lakehayli, S; El Khachibi, M; El Ouahli, M; Nadifi, S; Hakkou, F; Tazi, A

    2015-06-01

    Maternal distress has often been associated with cognitive deficiencies and drug abuse in rats. This study examined these behavioral effects in offspring of mothers stressed during gestation. To this end, pregnant dams were subjected to daily electric foot shocks during the last 10 days of pregnancy. We measured litter parameters and body weights of the descendants after weaning (21 days) and at adulthood (80 days). Afterwards, prenatally stressed and control rats' performances in the novel object recognition test were compared in order to evaluate their memory while others underwent the Water consumption test to assess the nicotine withdrawal intensity after perinatal manipulations. Meanwhile, another set of rats were sacrificed and 5HT1A receptors' mRNA expression was measured in the raphe nuclei by quantitative Real Time PCR. We noticed no significant influence of maternal stress on litter size and body weight right after weaning. However, control rats were heavier than the stressed rats in adulthood. The results also showed a significant decrease in the recognition score in rats stressed in utero compared to the controls. Moreover, a heightened anxiety symptom was observed in the prenatally stressed offspring following nicotine withdrawal. Additionally, the Real Time PCR method revealed that prenatal stress induced a significant decrease in 5HT1A receptors' levels in the raphe nuclei. Nicotine had a similar effect on these receptors' expression in both nicotine-treated control and prenatally stressed groups. Taken together, these findings suggest that the cognitive functions and drug dependence can be triggered by early adverse events in rats.

  1. Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats

    PubMed Central

    Zhang, Qing; Miller, Christopher; Bible, Jesse; Li, Jiliang; Xu, Xiaoqing; Mehta, Nozer; Gilligan, James; Vignery, Agnès; Scholz, Jodi A Carlson

    2012-01-01

    Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH). Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture. PMID:24710549

  2. Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats.

    PubMed

    Zhang, Qing; Miller, Christopher; Bible, Jesse; Li, Jiliang; Xu, Xiaoqing; Mehta, Nozer; Gilligan, James; Vignery, Agnès; Scholz, Jodi A Carlson

    2012-12-05

    Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH). Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture.

  3. Effects of aqueous extract from Asparagus officinalis L. roots on hypothalamic-pituitary-gonadal axis hormone levels and the number of ovarian follicles in adult rats

    PubMed Central

    Karimi Jashni, Hojatollah; Kargar Jahromi, Hossein; Ghorbani Ranjbary, Ali; Kargar Jahromi, Zahra; Khabbaz Kherameh, Zahra

    2016-01-01

    Background: Asparagus is a plant with high nutritional, pharmaceutical, and industrial values. Objective: The present study aimed to evaluate the effect of aqueous extract of asparagus roots on the hypothalamic-pituitary-gonadal axis hormones and oogenesis in female rats. Materials and Methods: In this experimental study, 40 adult female Wistar rats were divided into five groups, which consist 8 rats. Groups included control, sham and three experimental groups receiving different doses (100, 200, 400 mg/kg/bw) of aqueous extract of asparagus roots. All dosages were administered orally for 28 days. Blood samples were taken from rats to evaluate serum levels of Gonadotropin releasing hormone (GnRH), follicular stimulating hormone (FSH), Luteinal hormone (LH), estrogen, and progesterone hormones. The ovaries were removed, weighted, sectioned, and studied by light microscope. Results: Dose-dependent aqueous extract of asparagus roots significantly increased serum levels of GnRH, FSH, LH, estrogen, and progestin hormones compared to control and sham groups. Increase in number of ovarian follicles and corpus luteum in groups treated with asparagus root extract was also observed (p<0.05). Conclusion: Asparagus roots extract stimulates secretion of hypothalamic- pituitary- gonadal axis hormones. This also positively affects oogenesis in female rats. PMID:27200420

  4. EFFECT OF THE SELECTIVE NMDA NR2B ANTAGONIST, IFENPRODIL, ON ACUTE TOLERANCE TO ETHANOL-INDUCED MOTOR IMPAIRMENT IN ADOLESCENT AND ADULT RATS

    PubMed Central

    Ramirez, R. Liane; Varlinskaya, Elena I.; Spear, Linda P.

    2011-01-01

    Background Adolescent rats have been observed to be less sensitive than adults to a number of acute ethanol effects, including ethanol-induced motor impairment. These adolescent insensitivities may be related in part to the more rapid emergence of within session (acute) tolerance in adolescents than adults. Adolescent-related alterations in neural systems that serve as ethanol target sites, including changes in NMDA receptor subunit expression, may influence the responsiveness of adolescents to acute ethanol effects. The present study explored the role of NMDA NR2B receptors in the development of acute tolerance to ethanol-induced motor impairment in male adolescent (postnatal day [P]28–30), and adult (P68-70) Sprague-Dawley rats. Methods Motor impairing effects of ethanol on the stationary inclined plane and blood ethanol concentrations (BECs) were examined following challenge at each age with a functionally equivalent ethanol dose (adolescents: 2.25 g/kg; adults: 1.5 g/kg). Data were collected at two post-injection intervals (10 or 60 min) to compare rate of recovery from ethanol intoxication with BEC declines using the Radlow approach (Radlow, 1994) and changes in motor impairment/BEC ratios over time for assessing acute tolerance. Results Both vehicle-treated adolescent and adult animals showed similar acute tolerance development to the motor-impairing effects of ethanol at these functionally equivalent doses on the stationary inclined plane, as indexed by an increasing time-dependent dissociation between BECs and ethanol-induced motor impairment, with motor impairment declining faster than BECs, as well as by significant declines in motor impairment/BEC ratios over time. Acute tolerance development was reliably blocked by administration of the NR2B antagonist, ifenprodil, (5.0 mg/kg), in adult rats, whereas adolescents were affected by a higher dose (10.0 mg/kg). Conclusions These data support the suggestion that alterations in NMDA receptor systems

  5. The effects of an acute challenge with the NMDA receptor antagonists, MK-801, PEAQX, and ifenprodil, on social inhibition in adolescent and adult male rats.

    PubMed

    Morales, Melissa; Spear, Linda P

    2014-04-01

    NMDA antagonists consistently produce social inhibition in adult animals, although effects of these manipulations on social behavior of adolescents are relatively unknown. The aim of this study was to assess potential age differences in the socially inhibitory effects of the non-competitive NMDA antagonist, MK-801, as well as NR2 subunit selective effects, given the regional and developmental differences that exist for the NR2 subunit during ontogeny. In separate experiments, adolescent and adult male Sprague-Dawley rats were treated acutely with MK-801 (0, 0.05, 0.1, 0.2 mg/kg, i.p.), the NR2A antagonist, PEAQX (2.5, 5, 10, 20 mg/kg, s.c.), or the NR2B antagonist, ifenprodil (1.5, 3, 6, 12 mg/kg, i.p.), 10 min prior to a social interaction test. Adolescents required higher doses of MK-801 (0.1 and 0.2 mg/kg) to induce social suppression, whereas adults demonstrated reductions in social activity after all doses. Likewise, adolescents required higher doses of ifenprodil (6 and 12 mg/kg) to produce social inhibitory effects relative to adults (all doses). In contrast, adults were less sensitive to PEAQX than adolescents, with adults showing social inhibition after 20 mg/kg whereas adolescents showed this effect following 10 and 20 mg/kg. Although locomotor activity was generally reduced at both ages by all drugs tested, ANCOVAs using locomotor activity as a covariate revealed similar patterns of social inhibitory effects. Adolescents are less sensitive than adults to the disruption of social behavior by NMDA and NR2B-selective receptor antagonism, but not by an NR2A antagonist-age differences that may be related to different subunit expression patterns during development.

  6. The effects of an acute challenge with the NMDA receptor antagonists, MK-801, PEAQX, and ifenprodil, on social inhibition in adolescent and adult male rats

    PubMed Central

    Spear, Linda P.

    2013-01-01

    Rationale NMDA antagonists consistently produce social inhibition in adult animals, although effects of these manipulations on social behavior of adolescents are relatively unknown. Objectives The aim of this study was to assess potential age differences in the socially inhibitory effects of the non-competitive NMDA antagonist, MK-801, as well as NR2 subunit selective effects, given the regional and developmental differences that exist for the NR2 subunit during ontogeny. Methods In separate experiments, adolescent and adult male Sprague–Dawley rats were treated acutely with MK-801 (0, 0.05, 0.1, 0.2 mg/kg, i.p.), the NR2A antagonist, PEAQX (2.5, 5, 10, 20 mg/kg, s.c.), or the NR2B antagonist, ifenprodil (1.5, 3, 6, 12 mg/kg, i.p.), 10 min prior to a social interaction test. Results Adolescents required higher doses of MK-801 (0.1 and 0.2 mg/kg) to induce social suppression, whereas adults demonstrated reductions in social activity after all doses. Likewise, adolescents required higher doses of ifenprodil (6 and 12 mg/kg) to produce social inhibitory effects relative to adults (all doses). In contrast, adults were less sensitive to PEAQX than adolescents, with adults showing social inhibition after 20 mg/kg whereas adolescents showed this effect following 10 and 20 mg/kg. Although locomotor activity was generally reduced at both ages by all drugs tested, ANCOVAs using locomotor activity as a covariate revealed similar patterns of social inhibitory effects. Conclusions Adolescents are less sensitive than adults to the disruption of social behavior by NMDA and NR2B-selective receptor antagonism, but not by an NR2A antagonist—age differences that may be related to different subunit expression patterns during development. PMID:24043344

  7. Toluene effects on Oxidative Stress in Brain regions of Young-adult, Middleage,and Senescent Brown Norway Rats

    EPA Science Inventory

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound toluene. The objective was to test whether oxidative stress plays a role in the adver...

  8. Toluene effects on Oxidative Stress in Brain regions of Young-adult, Middleage,and Senescent Brown Norway Rats

    EPA Science Inventory

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound toluene. The objective was to test whether oxidative stress plays a role in the adver...

  9. Direct effects of ethane dimethanesulphonate on epididymal function in adult rats. An in vitro demonstration

    SciTech Connect

    Klinefelter, G.L.; Roberts, N.L.; Suarez, J.D.

    1992-01-01

    It was recently demonstrated that the Leydig cell toxicant ethane dimethanesulphonate (EDS) produces multiple effects on the epididymis after a single in vivo exposure. To determine whether any of the perturbations were mediated by a direct action of the compound, we used a novel system for the coculture of epididymal epithelial cells and sperm from the caput epididymidis. This system maintains the morphologic integrity and cell polarity of the epididymal epithelial cells before and during coculture, and the sperm recovered after coculture have intact plasma and acrosomal membranes. In addition, several functions required for epididymal sperm maturation are expressed, including the secretion of protein by the epididymal epithelium, the association of secreted protein with the plasma membrane of cocultured sperm, and the acquisition of progressive motility by cocultured sperm. In vitro exposure of epididymal epithelial cells and sperm to EDS results in a significant decline in protein secretion by the epithelial cells during coculture, and in particular, a dose-dependent decline in a 36- to 38-kd protein (PI 4.0 to 4.5) and a 34- to 36-kd protein (PI 4.5 to 5.0). Moreover, these and other proteins are not recovered from the sperm membrane of cocultured sperm after EDS treatment. Finally, EDS results in a dose-dependent decline in the percentage of both motile and progressively motile sperm recovered after coculture compared with that of sperm from untreated cocultures.

  10. The effect of 1,2,4-thiotriazolyl 5-mercaptoacetic acid new derivatives on lipid peroxidation in the heart from adult and old rats during stress.

    PubMed

    Davydov, V V; Shvets, V N

    2002-04-01

    The effect of 3-(4-pyridyl)-1,2,4-thiotriazolyl 5-mercaptoacetic acid kalium salt (Rumosol) and 3-(4-pyridyl)-1,2,4-thiotriazolyl 5-mercaptoacetic acid morpholinium salt (drug 2) on the concentration of Schiff base in myocardium of adult (10-12 months) and old (22-25 months) Wistar rats during immobilized stress were investigated. Here we show that the accumulation of Schiff base in the heart from both age groups was inhibited after injection of derivatives of 1,2,4-thiotriazolyl 5-mercaptoacetic acid prior to immobilization. Drug 2 possessed a two-fold higher pronounced capacity against Rumosol to inhibit the accumulation of Schiff base in the heart during stress. In myocardium from old rats, drug 2 decreased more effectively the stress-induced stimulation of lipid peroxidation as compared to dimethyl sulfoxide.

  11. Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats

    SciTech Connect

    Kodavanti, Prasada Rao S.; Royland, Joyce E.; Richards, Judy E.; Besas, Jonathan; MacPhail, Robert C.

    2011-11-15

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound, toluene. The objective was to test whether oxidative stress (OS) plays a role in the adverse effects caused by toluene exposure, and if so, if effects are age-dependent. OS parameters were selected to measure the production of reactive oxygen species (NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ-RD)), antioxidant homeostasis (total antioxidant substances (TAS), superoxide dismutase (SOD), {gamma}-glutamylcysteine synthetase ({gamma}-GCS), glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRD)), and oxidative damage (total aconitase and protein carbonyls). In this study, Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1 g/kg) in corn oil. Four hours later, frontal cortex, cerebellum, striatum, and hippocampus were dissected, quick frozen on dry ice, and stored at - 80 Degree-Sign C until analysis. Some parameters of OS were found to increase with age in select brain regions. Toluene exposure also resulted in increased OS in select brain regions. For example, an increase in NQO1 activity was seen in frontal cortex and cerebellum of 4 and 12 month old rats following toluene exposure, but only in the hippocampus of 24 month old rats. Similarly, age and toluene effects on glutathione enzymes were varied and brain-region specific. Markers of oxidative damage reflected changes in oxidative stress. Total aconitase activity was increased by toluene in frontal cortex and cerebellum at 12 and 24 months, respectively. Protein carbonyls in both brain regions and in all age groups were increased by toluene, but step-down analyses indicated toluene effects were statistically significant only in 12 month old rats. These results indicate changes in OS parameters with age and toluene exposure

  12. Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats.

    PubMed

    Kodavanti, Prasada Rao S; Royland, Joyce E; Richards, Judy E; Besas, Jonathan; Macphail, Robert C

    2011-11-01

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound, toluene. The objective was to test whether oxidative stress (OS) plays a role in the adverse effects caused by toluene exposure, and if so, if effects are age-dependent. OS parameters were selected to measure the production of reactive oxygen species (NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ-RD)), antioxidant homeostasis (total antioxidant substances (TAS), superoxide dismutase (SOD), γ-glutamylcysteine synthetase (γ-GCS), glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRD)), and oxidative damage (total aconitase and protein carbonyls). In this study, Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1g/kg) in corn oil. Four hours later, frontal cortex, cerebellum, striatum, and hippocampus were dissected, quick frozen on dry ice, and stored at -80°C until analysis. Some parameters of OS were found to increase with age in select brain regions. Toluene exposure also resulted in increased OS in select brain regions. For example, an increase in NQO1 activity was seen in frontal cortex and cerebellum of 4 and 12 month old rats following toluene exposure, but only in the hippocampus of 24 month old rats. Similarly, age and toluene effects on glutathione enzymes were varied and brain-region specific. Markers of oxidative damage reflected changes in oxidative stress. Total aconitase activity was increased by toluene in frontal cortex and cerebellum at 12 and 24 months, respectively. Protein carbonyls in both brain regions and in all age groups were increased by toluene, but step-down analyses indicated toluene effects were statistically significant only in 12month old rats. These results indicate changes in OS parameters with age and toluene exposure resulted in oxidative

  13. Neonatal DSP-4 treatment modifies antinociceptive effects of the CB1 receptor agonist methanandamide in adult rats.

    PubMed

    Korossy-Mruk, Eva; Kuter, Katarzyna; Nowak, Przemysław; Szkilnik, Ryszard; Rykaczewska-Czerwinska, Monika; Kostrzewa, Richard M; Brus, Ryszard

    2013-01-01

    To study the influence of the central noradrenergic system on antinociceptive effects mediated by the CB(1)-receptor agonist methanandamide, intact rats were contrasted with rats in which noradrenergic nerves were largely destroyed shortly after birth with the neurotoxin DSP-4 [N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (50 mg/kg sc × 2, P1 and P3); zimelidine (10 mg/kg sc, 30 min pretreatment, selective serotonin reuptake inhibitor). When rats attained 10 weeks of age, monoamine and their metabolite concentrations were determined in the frontal cortex, thalamus, and spinal cord by an HPLC/ED method. Antinociceptive effects after methanandamide (10 mg/kg ip) apply were evaluated by a battery of tests. In addition, immunohistochemistry and densitometric analysis of the cannabinoid CB(1) receptor in the rat brain was performed. DSP-4 lesioning was associated with a reduction in norepinephrine content of the frontal cortex (>90 %) and spinal cord (>80 %) with no changes in the thalamus. Neonatal DSP-4 treatment produced a significant reduction in the antinociceptive effect of methanandamide in the tail-immersion test, hot-plate test and writhing tests. In the paw pressure and formalin hind paw tests results were ambiguous. These findings indicate that the noradrenergic system exerts a prominent influence on analgesia acting via the cannabinoid system in brain, without directly altering CB(1) receptor density in the brain.

  14. Acute Effect of Manganese on Hypothalamic Luteinizing Hormone Releasing Hormone Secretion in Adult Male Rats: Involvement of Specific Neurotransmitter Systems

    PubMed Central

    Prestifilippo, Juan Pablo; Fernández-Solari, Javier; De Laurentiis, Andrea; Mohn, Claudia Ester; de la Cal, Carolina; Reynoso, Roxana; Dees, W. Les; Rettori, Valeria

    2008-01-01

    Manganese chloride (MnCl2) is capable of stimulating luteinizing hormone releasing hormone (LHRH) secretion in adult male Sprague-Dawley rats through the activation of the hypothalamic nitric oxide/cyclic guanosine monophosphate (cGMP)/protein kinase G pathway. The present study aimed to determine the involvement of specific neurotransmitters involved in this action. Our results indicate that dopamine, but not glutamic acid and prostaglandinds, mediates the MnCl2 stimulated secretion of LHRH from medial basal hypothalami in vitro, as well as increases the activity of nitric oxide synthase. Furthermore, a biphasic response was observed in that gamma aminobutyric acid (GABA) release was also increased, which acts to attenuate the MnCl2 action to stimulate LHRH secretion. Although it is clear that manganese (Mn+2) can acutely induce LHRH secretion in adult males, we suggest that the additional action of MnCl2 to release GABA, a LHRH inhibitor, may ultimately contribute to suppressed reproductive function observed in adult animals following exposure to high chromic levels of Mn+2. PMID:18603625

  15. Synergistic effect between prelimbic 5-HT3 and CB1 receptors on memory consolidation deficit in adult male Sprague-Dawley rats: An isobologram analysis.

    PubMed

    Ahmadi-Mahmoodabadi, N; Nasehi, M; Emam Ghoreishi, M; Zarrindast, M-R

    2016-03-11

    The serotonergic system has often been defined as a neuromodulator system, and is specifically involved in learning and memory via its various receptors. Serotonin is involved in many of the same processes affected by cannabinoids. The present study investigated the influence of bilateral post-training intra-prelimbic (PL) administrations of serotonergic 5-hydroxytryptamine type-3 (5-HT3) receptor agents on arachidonylcyclopropylamide (ACPA) (cannabinoid CB1 receptor agonist)-induced amnesia, using the step-through inhibitory avoidance (IA) task to assess memory in adult male Sprague-Dawley rats. The results indicated that sole intra-PL microinjection of ACPA (0.1 and 0.5 μg/rat) and 5-HT3 serotonin receptor agonist (m-Chlorophenylbiguanide hydrochloride, m-CPBG; 0.001, 0.01 and 0.1 μg/rat) impaired, whereas Y-25130 (a selective 5-HT3 serotonin receptor antagonist; 0.001 and 0.01 and 0.1 μg/rat) did not alter IA memory consolidation, by itself. Moreover, intra-PL administration of subthreshold dose of m-CPBG (0.0005 μg/rat) potentiated, while Y-25130 (0. 1 μg/rat) restored ACPA-induced memory consolidation deficit. The isobologram analysis showed that there is a synergistic effect between ACPA and m-CPBG on memory consolidation deficit. These findings suggest that 5-HT3 receptor mechanism(s), at least partly, play(s) a role in modulating the effect of ACPA on memory consolidation in the PL area.

  16. Effects of ethanol during adolescence on the number of neurons and glia in the medial prefrontal cortex and basolateral amygdala of adult male and female rats

    PubMed Central

    Koss, W.A.; Sadowski, R.N.; Sherrill, L.K.; Gulley, J.M.; Juraska, J.M.

    2012-01-01

    Human adolescents often consume alcohol in a binge-like manner at a time when changes are occurring within specific brain structures, such as the medial prefrontal cortex (mPFC) and the basolateral nucleus of the amygdala (BLN). In particular, neuron and glia number are changing in both of these areas in the rat between adolescence and adulthood (Markham et al., 2007; Rubinow and Juraska, 2009). The current study investigated the effects of ethanol exposure during adolescence on the number of neurons and glia in the adult mPFC and BLN in Long-Evans male and female rats. Saline or 3 g/kg ethanol was administered between postnatal days (P) 35–45 in a binge-like pattern, with 2 days of injections followed by 1 day without an injection. Stereological analyses of the ventral mPFC (prelimbic and infralimbic areas) and the BLN were performed on brains from rats at 100 days of age. Neuron and glia densities were assessed with the optical disector and then multiplied by the volume to calculate the total number of neurons and glia. In the adult mPFC, ethanol administration during adolescence resulted in a decreased number of glia in males, but not females, and had no effect on the number of neurons. Adolescent ethanol exposure had no effects on glia or neuron number in the BLN. These results suggest that glia cells in the prefrontal cortex are particularly sensitive to binge-like exposure to ethanol during adolescence in male rats only, potentially due to a decrease in proliferation in males or protective mechanisms in females. PMID:22627163

  17. The effects of acute and chronic administration of phosphatidylserine on cell proliferation and survival in the dentate gyrus of adult and middle-aged rats.

    PubMed

    Maragno, Heloisa; Rodella, Patricia; Silva Freitas, Josiane da; Fernando Takase, Luiz

    2015-06-03

    Phosphatidylserine (PS) is an acidic phospholipid that is widely used as an alternative and/or complementary treatment of cognitive impairments. We hypothesize that these changes may be attributable, at least in part, to alterations in hippocampal neurogenesis. The aim of the present study was to investigate the effects of acute and chronic PS administration on hippocampal cell proliferation and survival in adult (5 months old) and middle-aged (12 months old) male Wistar rats. PS was injected daily (50mg/kg, i.p.) during 7 days (acute experiment) or 21 days (chronic experiment). To label newly generated cells, rats received a single BrdU injection (200mg/kg, i.p.) one day before PS treatment. The object recognition test was performed, and the rats were perfused. The brains were removed and processed with immunohistochemistry techniques for Ki-67 (cell proliferation) and BrdU (cell survival). The acute and chronic regimens were unable to promote cognitive improvement in either age group in the object recognition test. The analysis of cell proliferation showed a significant increase in the number of Ki-67-positive cells after acute and chronic PS administration in both age groups. The analysis of cell survival showed that acute and chronic PS administration increased the number of BrdU-positive cells only in adult animals.

  18. Electroencephalographic and behavioral effects of intracerebroventricular or intraperitoneal injections of toxic honey extract in adult Wistar rats and GAERS.

    PubMed

    Kuru, Pinar; Torun, Merve; Halac, Hande Melike; Temiz, Gozde; Iskender, Ece; Karamahmutoglu, Tugba; Idrizoglu, Medine Gulcebi; Onat, Filiz Yilmaz

    2014-12-01

    Toxic honey, containing grayanotoxin, is obtained from nectar and polen of rhododendron. Consumed in excess it produces seizures and convulsions. In order to investigate whether the toxic honey extract can be used as a seizure model, we examined the electroencephalographic (EEG) and motor effects of intracerebroventricular (icv) or intraperitoneal (ip) injection of toxic honey extract in Wistar rats or in genetic absence epilepsy rats from Strasbourg (GAERS). Male Wistar rats or GAERS were stereotaxically implanted with bilateral cortical recording electrodes in all ip groups and cannula in the icv groups. Based on the previous study, an extract was obtained from the non-toxic and toxic honey. After the injection of the non-toxic or toxic honey extract, seizure stages and changes in EEG were evaluated from 9 am to noon. The icv administration of toxic honey extract produced stage 4 seizures and bilateral cortical spikes within 30-60 min and these effects disappeared after 120 min in Wistar rats or GAERS. The mean of bilateral cortical spike acitivity in EEG of Wistar rats was 804.2 ± 261.0 s in the 3-h period. After the icv administration of toxic honey extract to GAERS, the mean duration of spike-and-wave discharges (SWDs) in GAERS significantly decreased during the first 60 min and then returned to baseline level. Ip injection of toxic honey extract caused no seizure and no change in EEG in either GAERS or Wistars. These results suggest that the icv administration of toxic honey extract can be used as a seizure model.

  19. The effects of age on the morphometry of the cervical spinal cord and spinal column in adult rats: an MRI-based study.

    PubMed

    Laing, Andrew C; Brenneman, Elora C; Yung, Andrew; Liu, Jie; Kozlowski, Piotr; Oxland, Thomas

    2014-10-01

    Rat models are commonly used to investigate the pathophysiological pathways and treatment outcomes after spinal cord injury (SCI). The high incidence of fall-induced SCI in older adults has created a need for aging models of SCI in rats to investigate potential age-related differences in SCI severity and outcomes. The aims of this study were to determine the influences of age and vertebral level on the geometries of the cervical spinal cord and spinal column in a rat model. Three young (3 months) and three aged (12 months) Fischer 344 rats were imaged in a high field (7 T) small-animal magnetic resonance imaging system. All spinal cord geometry variables (including depth, width, and axial cross-sectional area) and one spinal canal variable (depth) were significantly larger in the aged specimens by an average of 8.1%. There were main effects of vertebral level on all spinal cord variables and four spinal canal variables with values generally larger at C4 as compared to C6 (average increases ranged from 5.7% to 12.9% in spinal cord measures and 5.4% to 6.8% in spinal canal measures). High inter-rater reliability between two measurers was observed with a mean intraclass correlation of 0.921 and percent difference of 0.9% across all variables measured. This study clearly demonstrates that cervical spinal cord geometry changes between the ages of 3 and 12 months in Fischer 344 rats. This information can aid in the planning and interpretation of studies that use a rat model to investigate the influence of age on cervical SCI. © 2014 Wiley Periodicals, Inc.

  20. The effect of supplemental food on the growth rates of neonatal, young, and adult cotton rats ( Sigmodon hispidus) in northeastern Kansas, USA

    NASA Astrophysics Data System (ADS)

    Eifler, Maria A.; Slade, Norman A.; Doonan, Terry J.

    2003-09-01

    In food-limited populations, the presence of extra food resources can influence the way individuals allocate energy to growth and reproduction. We experimentally increased food available to cotton rats ( Sigmodon hispidus) near the northern limit of their range over a 2-year period and tested the hypothesis that seasonal growth rates would be enhanced by supplemental food during winter and spring when natural food levels are low. We also examined whether additional food resources were allocated to somatic growth or reproductive effort by pregnant and lactating females. The effect of supplemental food on growth varied with mass and season, but did not influence the growth rates of most cotton rats during spring and winter. In winter, small animals on supplemented grids had higher growth rates than small animals on control grids, but females in spring had lower growth rates under supplemented conditions. Growth rates of supplemented cotton rats were enhanced in summer. Northern cotton rat populations may use season-specific foraging strategies, maximizing energy intake during the reproductive season and minimizing time spent foraging in winter. Adult females invest extra resources in reproduction rather than in somatic growth. Pregnant females receiving supplemental food had higher growth rates than control females, and dependent pups (≤ 1 month of age) born to supplemented mothers had higher growth rates than those born to control mothers. Increased body size seems to confer an advantage during the reproductive season, but has no concomitant advantage to overwinter survival.

  1. The developmental effects of extremely low frequency electric fields on visual and somatosensory evoked potentials in adult rats.

    PubMed

    Gok, Deniz Kantar; Akpinar, Deniz; Hidisoglu, Enis; Ozen, Sukru; Agar, Aysel; Yargicoglu, Piraye

    2016-01-01

    The purpose of our study was to investigate the developmental effects of extremely low frequency electric fields (ELF-EFs) on visual evoked potentials (VEPs) and somatosensory-evoked potentials (SEPs) and to examine the relationship between lipid peroxidation and changes of these potentials. In this context, thiobarbituric acid reactive substances (TBARS) levels were determined as an indicator of lipid peroxidation. Wistar albino female rats were divided into four groups; Control (C), gestational (prenatal) exposure (Pr), gestational+ postnatal exposure (PP) and postnatal exposure (Po) groups. Pregnant rats of Pr and PP groups were exposed to 50 Hz electric field (EF) (12 kV/m; 1 h/day), while those of C and Po groups were placed in an inactive system during pregnancy. Following parturition, rats of PP and Po groups were exposed to ELF-EFs whereas rats of C and Pr groups were kept under the same experimental conditions without being exposed to any EF during 68 days. On postnatal day 90, rats were prepared for VEP and SEP recordings. The latencies of VEP components in all experimental groups were significantly prolonged versus C group. For SEPs, all components of PP group, P2, N2 components of Pr group and P1, P2, N2 components of Po group were delayed versus C group. As brain TBARS levels were significantly increased in Pr and Po groups, retina TBARS levels were significantly elevated in all experimental groups versus C group. In conclusion, alterations seen in evoked potentials, at least partly, could be explained by lipid peroxidation in the retina and brain.

  2. Paradoxical effects of injection stress and nicotine exposure experienced during adolescence on learning in a serial multiple choice (SMC) task in adult female rats.

    PubMed

    Renaud, Samantha M; Pickens, Laura R G; Fountain, Stephen B

    2015-01-01

    Nicotine exposure in adolescent rats has been shown to cause learning impairments that persist into adulthood long after nicotine exposure has ended. This study was designed to assess the extent to which the effects of adolescent nicotine exposure on learning in adulthood can be accounted for by adolescent injection stress experienced concurrently with adolescent nicotine exposure. Female rats received either 0.033 mg/h nicotine (expressed as the weight of the free base) or bacteriostatic water vehicle by osmotic pump infusion on postnatal days 25-53 (P25-53). Half of the nicotine-exposed rats and half of the vehicle rats also received twice-daily injection stress consisting of intraperitoneal saline injections on P26-53. Together these procedures produced 4 groups: No Nicotine/No Stress, Nicotine/No Stress, No Nicotine/Stress, and Nicotine/Stress. On P65-99, rats were trained to perform a structurally complex 24-element serial pattern of responses in the serial multiple choice (SMC) task. Four general results were obtained in the current study. First, learning for within-chunk elements was not affected by either adolescent nicotine exposure, consistent with past work (Pickens, Rowan, Bevins, and Fountain, 2013), or adolescent injection stress. Thus, there were no effects of adolescent nicotine exposure or injection stress on adult within-chunk learning typically attributed to rule learning in the SMC task. Second, adolescent injection stress alone (i.e., without concurrent nicotine exposure) caused transient but significant facilitation of adult learning restricted to a single element of the 24-element pattern, namely, the "violation element," that was the only element of the pattern that was inconsistent with pattern structure. Thus, adolescent injection stress alone facilitated violation element acquisition in adulthood. Third, also consistent with past work (Pickens et al., 2013), adolescent nicotine exposure, in this case both with and without adolescent

  3. Paradoxical Effects of Injection Stress and Nicotine Exposure Experienced During Adolescence on Learning in a Serial Multiple Choice (SMC) Task in Adult Female Rats

    PubMed Central

    Renaud, Samantha M.; Pickens, Laura R. G.; Fountain, Stephen B.

    2015-01-01

    Nicotine exposure in adolescent rats has been shown to cause learning impairments that persist into adulthood long after nicotine exposure has ended. This study was designed to assess the extent to which the effects of adolescent nicotine exposure on learning in adulthood can be accounted for by adolescent injection stress experienced concurrently with adolescent nicotine exposure. Female rats received either 0.033 mg/hr nicotine (expressed as the weight of the free base) or bacteriostatic water vehicle by osmotic pump infusion on postnatal days 25-53 (P25-53). Half of the nicotine-exposed rats and half of the vehicle rats also received twice-daily injection stress consisting of intraperitoneal saline injections on P26-53. Together these procedures produced 4 groups: No Nicotine / No Stress, Nicotine / No Stress, No Nicotine / Stress, and Nicotine / Stress. On P65-99, rats were trained to perform a structurally complex 24-element serial pattern of responses in the serial multiple choice (SMC) task. Four general results were obtained in the current study. First, learning for within-chunk elements was not affected by either adolescent nicotine exposure, consistent with past work (Pickens, Rowan, Bevins, & Fountain, 2013), or adolescent injection stress. Thus, there were no effects of adolescent nicotine exposure or injection stress on adult within-chunk learning typically attributed to rule learning in the SMC task. Second, adolescent injection stress alone (i.e., without concurrent nicotine exposure) caused transient but significant facilitation of adult learning restricted to a single element of the 24-element pattern, namely, the “violation element,” that was the only element of the pattern that was inconsistent with pattern structure. Thus, adolescent injection stress alone facilitated violation element acquisition in adulthood. Third, also consistent with past work (Pickens et al., 2013), adolescent nicotine exposure, in this case both with and without

  4. Effects of amphetamine exposure in adolescence or young adulthood on inhibitory control in adult male and female rats

    PubMed Central

    Hammerslag, Lindsey R.; Waldman, Alex J.; Gulley, Joshua M.

    2014-01-01

    Heightened impulsivity is a feature of some psychiatric disorders, including addiction, that also have sex-specific patterns of expression. The relationship between addiction and impulsivity may be driven by drug-induced changes in behavior caused by long term adaptations in signaling within the medial prefrontal cortex (mPFC). Here, we used a response inhibition task that is sensitive to changes in mPFC function to examine the effects of sex and exposure to amphetamine (AMPH) on impulsive action and vigilance. We also examined drug-induced alterations in glutamatergic and dopaminergic signaling through challenge injections with the NMDA receptor antagonist MK-801 (dizocilpine) and AMPH. Male and female Sprague Dawley rats were injected (i.p.) with saline or 3 mg/kg AMPH every other day during adolescence (postnatal day (P) 27–45) or adulthood (P85–103). Starting on P125–135, rats were tested for their ability to lever press for a food reward during periods of signaled availability and withhold responding during a “premature response” phase. In experiment 1, rats received challenge injections (i.p.) of MK-801 and AMPH followed by tests of task performance and locomotor activity. In experiment 2, rats received intra-mPFC infusion of MK-801. We found that females had better inhibitory control and poorer vigilance than males and that AMPH exposure had both sex- and age-of-exposure dependent effects on impulsivity. Systemic drug challenges disrupted task performance, particularly in females, and increased impulsivity while intra-mPFC infusions had modest effects. AMPH exposure did not affect responses to drug challenges. Together, these results suggest that sex mediates both trait and drug-induced impulsivity. PMID:24462963

  5. Effects of acute microinjections of thyroid hormone to the preoptic region of euthyroid adult male rats on sleep and motor activity.

    PubMed

    Martin, Joseph V; Giannopoulos, Phillip F; Moffett, Steven X; James, Thomas D

    2013-06-21

    In adult brain tissue, thyroid hormones are known to have multiple effects which are not mediated by chronic influences of the hormones on heterodimeric thyroid hormone nuclear receptors. Previous work has shown that acute microinjections of l-triiodothyronine (T3) to the preoptic region significantly influence EEG-defined sleep in hypothyroid rats. The current study examined the effects of similar microinjections in euthyroid rats. In 7 rats with histologically confirmed microinjection sites bilaterally placed in the preoptic region, slow-wave sleep time was significantly decreased, but REM and waking were increased as compared to vehicle-injected controls. The EEG-defined parameters were significantly influenced by the microinjections in a biphasic dose-response relationship; the lowest (0.3μg) and highest (10μg) doses tested were without significant effect while intermediate doses (1 and 3μg) induced significant differences from controls. There were significant diurnal variations in the measures, yet no significant interactions between the effect of hormone and time of day were demonstrated. Core body temperature was not significantly altered in the current study. The demonstration of effects of T3 within hours instead of days is consistent with a rapid mechanism of action such as a direct influence on neurotransmission. Since the T3-mediated effects were robust in the current work, euthyroid rats retain thyroid hormone sensitivity which would be needed if sleep-regulatory mechanisms in the preoptic region are continuously modulated by the hormones. This article is part of a Special Issue entitled LInked: BRES-D-12-01552 & BRES-D-12-01363R2.

  6. Effects of hypothyroidism and endocrine disruptor-dependent non-thyroidal illness syndrome on the GnRH-gonadotroph axis of the adult male rat.

    PubMed

    Toni, R; Della Casa, C; Castorina, S; Cocchi, D; Celotti, F

    2005-01-01

    Effects of primary hypothyroidism (HYPO) on the male gonadal axis are controversial, with only scanty data on the gonadotroph cell response and no information on GnRH tuberoinfundibular neurons, even in animal models. HYPO has been reported to variably induce hypogonadotropic hypogonadism, a hypergonadotropic state, or to have no effects on basal levels of pituitary gonadotropins, both in adult male rats and humans. Similarly, the exogenous administration of GnRH to HYPO rats and humans may increase or decrease gonadotropin secretion. Since inhibitory effects of HYPO on the GnRH-gonadotropin axis are reversed by replacement with L-T4, it has been suggested that thyroid hormone (TH) may regulate tuberoinfundibular GnRH and pituitary gonadotropin biosynthesis and/or secretion. To shed light on this hypothesis, we conducted immunocytochemical studies on the distribution and immunostaining characteristics of hypophysiotropic GnRH neurons, LH, PRL and vasoactive intestinal polypeptide (VIP) immunoreactive (IR) cells in the pituitary of adult, male rats. We show that HYPO reduces IR-GnRH in a restricted population of tuberoinfundibular perikarya and their proximal axons compared to euthyroid controls, but increases IR-VIP both in pituitary cells in direct association with LH-gonadotrophs and within IR-LH cells, itself. We propose that VIP may serve as a juxtacrine/paracrine/autocrine regulator of LH secretion and that, when GnRH biosynthesis is reduced by HYPO, gonadotropin secretion may be rescued by local activating effects of VIP. Polychlorinated biphenyls (PCB), industry toxicants found in food and water, also have inhibitory effects on the gonadal axis, decreasing fertility and suppressing basal and GnRHinduced LH release in male rats. Since PCB may also exert endocrine disruptor-dependent (EDD) effects on the thyroid axis producing a non-thyroidal illness syndrome (NTIS) (coined EDD-NTIS), we developed a rat model of EDD-NTIS to determine whether central

  7. Effect of protein-energy malnutrition in early life on the dimensions and bone quality of the adult rat mandible.

    PubMed

    Alippi, Rosa M; Meta, Margarita D; Olivera, María I; Bozzini, Clarisa; Schneider, Peter; Meta, Isaac F; Bozzini, Carlos E

    2002-01-01

    Morphological and biomechanical features of the mandible are negatively affected by protein-energy malnutrition, whose effects are apparently dependent on the time of life of application. The aim here was to investigate, in neonatal rats nursed by dams put on a protein-free diet to depress milk production and thus create a state of protein-energy malnutrition in the offspring, subsequent growth and long-term effects by analyzing mandibular dimensions and bone quality in adulthood. Pregnant Wistar rats were fed a 20% protein diet (control) or a protein-free diet (malnourished) to obtain normal or subnormal milk production, respectively. After weaning, the offspring (males) were fed a 20% protein diet for 70 days. The dimensions of their excised mandibles were measured directly between anatomical points; the geometry and material quality of mandibular bone were assessed by peripheral quantitative computed tomography. Pups suckling from malnourished dams weighed 49.4% of those suckling from control dams at weaning; the actual difference between control and malnourished pups was 25.1g, which persisted until day 91 of age, indicating the absence of catch-up growth. As with body size, the mandibular base length, height and area (an index of mandibular size) were significantly smaller in malnourished than control rats at the end of the study. The mandibular cortical area, volumetric cortical bone mineral content and volumetric cortical bone mineral density assessed by peripheral quantitative computed tomography were similar in both groups of rats at the end of the observation period, but there was a significant reduction in the cortical axial moment of inertia in malnourished rats at this time of postnatal life. These findings suggest that catch-up growth was incomplete in rats malnourished during the suckling period and that the adaptation of mandibular bone architecture to body growth was apparently insufficient to attain normal values, thus not allowing complete

  8. Protective effect of aqueous seed extract of Vitis Vinifera against oxidative stress, inflammation and apoptosis in the pancreas of adult male rats with diabetes mellitus.

    PubMed

    Adam, Siti Hajar; Giribabu, Nelli; Kassim, Normadiah; Kumar, Kilari Eswar; Brahmayya, Manuri; Arya, Aditya; Salleh, Naguib

    2016-07-01

    Protective effects of Vitis Vinifera seed aqueous extract (VVSAE) against pancreatic dysfunctions and elevation of oxidative stress, inflammation and apoptosis in the pancreas in diabetes were investigated. Histopathological changes in the pancreas were examined under light microscope. Blood and pancreas were collected from adult male diabetic rats receiving 28days treatment with VVSAE orally. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin and lipid profile levels and activity levels of anti-oxidative enzymes (superoxide dismutase-SOD, catalase-CAT and glutathione peroxidase-GPx) in the pancreas were determined by biochemical assays. Histopathological changes in the pancreas were examined under light microscopy and levels of insulin, glucose transporter (GLUT)-2, tumor necrosis factor (TNF)-α, Ikkβ and caspase-3 mRNA and protein were analyzed by real-time PCR (qPCR) and immunohistochemistry respectively. Radical scavenging activity of VVSAE was evaluated by in-vitro anti-oxidant assay while gas chromatography-mass spectrometry (GC-MS) was used to identify the major compounds in the extract. GC-MS analyses indicated the presence of compounds that might exert anti-oxidative, anti-inflammatory and anti-apoptosis effects. Near normal FBG, HbAIc, lipid profile and serum insulin levels with lesser signs of pancreatic destruction were observed following administration of VVSAE to diabetic rats. Higher insulin, GLUT-2, SOD, CAT and GPx levels but lower TNF-α, Ikkβ and caspase-3 levels were also observed in the pancreas of VVSAE-treated diabetic rats (p<0.05 compared to non-treated diabetic rats). The extract possesses high in-vitro radical scavenging activities. In conclusions, administration of VVSAE to diabetic rats could help to protect the pancreas against oxidative stress, inflammation and apoptosis-induced damage while preserving pancreatic function near normal in diabetes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Effects of CB1 receptor agonism and antagonism on behavioral fear and physiological stress responses in adult intact, ovariectomized, and estradiol-replaced female rats.

    PubMed

    Simone, J J; Malivoire, B L; McCormick, C M

    2015-10-15

    There is growing interest in the development of cannabis-based therapies for the treatment of fear and anxiety disorders. There are a few studies, but none in females, of the effects of the highly selective cannabinoid receptor type 1 (CB1) agonist, arachidonyl 2'-chlorethylamide (ACEA), on behavioral fear. In experiment 1 involving gonadally-intact females, ACEA (either 0.1 or 0.01 mg/kg) was without effect in the elevated plus maze (EPM), and the lower dose decreased anxiety in the open field test (OFT). AM251 increased anxiety in the EPM and decreased locomotor activity in the OFT. Twenty-four hours after fear conditioning, neither ACEA nor AM251 affected generalized fear or conditioned fear recall. AM251 and 0.1 mg/kg ACEA impaired, and 0.01 mg/kg ACEA enhanced, within-session fear extinction. AM251 increased plasma corticosterone concentrations after the fear extinction session, whereas ACEA was without effect. Based on evidence that estradiol may moderate the effects of CB1 receptor signaling in females, experiment 2 involved ovariectomized (OVX) rats provided with 10-μg 17β-Estradiol and compared with OVX rats without hormone replacement (oil vehicle). Irrespective of hormone treatment, AM251 increased anxiety in the EPM, whereas ACEA (0.01 mg/kg) was without effect. Neither hormone nor drug altered anxiety in the OFT, but estradiol increased and AM251 decreased distance traveled. After fear conditioning, AM251 decreased generalized fear. Neither hormone nor drug had any effect on recall or extinction of conditioned fear, however, ACEA and AM251 increased fear-induced plasma corticosterone concentrations. Further, when results with intact rats were compared with those from OVX rats, gonadal status did not moderate the effects of either AM251 or ACEA, although OVX displayed greater anxiety and fear than did intact rats. Thus, the effects of CB1 receptor antagonism and agonism in adult female rats do not depend on ovarian estradiol. Copyright © 2015 IBRO

  10. Effects of a mixture of pesticides on the adult female reproductive system of Sprague-Dawley, Wistar, and Lewis rats.

    PubMed

    Pascotto, Viviane M; Guerra, Marina T; Franci, Janete Aparecida Anselmo; de Camargo, João Lauro V; Kempinas, Wilma G; Franchi, Carla A S

    2015-01-01

    The Brazilian federal government Agency for Health Surveillance detected pesticide residues in fresh food available for consumers all over the country. The current study investigated the effects of a mixture of some of those pesticides (dichlorvos, dicofol, dieldrin, endosulfan, and permethrin) on the reproductive system of Sprague-Dawley (SD), Wistar (WT), and Lewis (LEW) rats. Female rats from each strain were randomized into three experimental groups and were fed a control diet or diets added with pesticides mixture at their respective no-observed-effect level (NOEL)/no-observed-adverse-effect level (NOAEL) (low dose) (mg/kg/d): dichlorvos (0.23), dicofol (0.5), dieldrin (0.025), endosulfan (0.7), permethrin (5), or lowest-observed-effect level (LOEL)/lowest-effect level (LEL)/ lowest-observed-adverse-effect level (LOAEL) (toxically effective dose) (mg/kg/d): dichlorvos (2.3), dicofol (2.1), dieldrin (0.05), endosulfan (3.8), and permethrin (25) as reported in the literature. Euthanasia was performed between wk 10 and 12, during the estrous stage. Decreased body weights gain (SD and WT) and increased liver weights (SD, WT, and LEW) were observed in each strain fed the pesticides mixture at the higher levels. At that dose level, rat strains also varied in their responses regarding the estrous cycle, hormonal levels, and number of developing ovarian follicles. The studied mixture of pesticides was found to interfere with the female reproductive system when individual pesticides were mixed above a certain level, indicating a threshold exists for each of the strains studied.

  11. Effect of BDNF-plasma-collagen matrix controlled delivery system on the behavior of adult rats neural stem cells.

    PubMed

    Yang, Zhaoyang; Qiao, Hui; Sun, Zhiwei; Li, Xiaoguang

    2013-02-01

    The neurogenesis amount in central nervous system (CNS) stimulated by the injury or diseases is so small that neural stem cells (NSCs) cannot specifically differentiate into the ideal phenotypes to repair the injured CNS. The transplanted exogenous NSCs also have such problems as poor survival and insufficient neuronal differentiation. In this study, the behavior of NSCs from the spinal cord of adult rats was compared at the neurosphere level after the respective addition of the brain-derived neurotrophic factor (BDNF) daily, the BDNF-loaded plasma-collagen matrix, the plasma-collagen matrix alone, or the defined medium alone. The results suggested that the BDNF, either in the control release form or in the soluble form, initiated NSCs proliferation and differentiation by activating receptors Trk B and p75NTR. BDNF also increased the differentiation percentage of adult NSCs into neurons and supported the long-term cell survival and growth. The BDNF was stably released by the plasma-collagen matrix for up to 21 days. The plasma-collagen matrix alone showed its biocompatibility with cells by facilitating the adhesion, survival, and differentiation of NSCs. The NSCs in the defined medium alone group showed poor survival and a very low level of neuronal differentiation and proliferation abilities than above three groups. This study suggested that the BDNF-loaded plasma-collagen matrix may provide a promising means to resolve either the poor survival and insufficient neuronal differentiation of transplanted exogenous NSCs, or stimulating the intrinsic NSCs to proliferate and differentiate into neurons so as to repair the injured adult CNS. Copyright © 2012 Wiley Periodicals, Inc.

  12. Protective effects of vitamin C and selenium supplementation on methomyl-induced tissue oxidative stress in adult rats.

    PubMed

    Djeffal, Assia; Messarah, Mahfoud; Boumendjel, Amel; Kadeche, Lilia; Feki, Abdelfattah El

    2015-01-01

    Methomyl (MET) is used worldwide in agriculture and health programs. Besides its advantages in the agriculture, it causes several toxic effects. The objective of this study was to examine the potential ability of vitamin C and/or selenium (Se), to alleviate the oxidative damage parameters, against MET-induced changes in blood biochemical markers and oxidative damage in liver and kidney of male Wistar rats. The animals were randomized into five groups of eight each: group I served as control rats; group II received MET (8 mg/kg body weight (BW)) in drinking water; group III received both MET and vitamin C (200 mg/kg BW; by intraperitoneal injection); group IV received both MET and Se (0.6 mg/100 g BW). Animals of group V were treated with MET, vitamin C and Se. A significant increase in the levels of hepatic markers enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase) was determined. Furthermore, renal markers such as urea and creatinine were increased in MET-treated rats. Additionally, serum cholesterol and triglycerides were significantly enhanced. Exposure of rats to MET caused significant increase in malondialdehyde levels, thus causing a drastic alteration in antioxidant defense system, particularly in the activities of catalase and glutathione-S-transferase and glutathione peroxidase. However, simultaneous supplementation with vitamin C and Se restored these parameters partially. In conclusion, the results of the current study revealed that MET-induced toxicity caused perturbations of some biochemical parameters, lipid peroxidation and alterations in the antioxidant enzymes in liver and kidney homogenates. Administration of vitamin C and Se exhibited protective effect by inhibiting MET-induced toxicity in liver and kidney. © The Author(s) 2012.

  13. Early postnatal effects of noopept and piracetam on declarative and procedural memory of adult male and female rats.

    PubMed

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

    2005-06-01

    We studied the effect of a new nootropic dipeptide Noopept and reference nootropic preparation piracetam injected subcutaneously on days 8-20 of life on learning of alternative feeding response in a 6-arm-maze in male and female rats. Early postnatal administration of Noopept disturbed the dynamics of learning by parameters of declarative and procedural memory. Piracetam impaired learning by parameters of procedural, but not declarative memory (only in males). Both preparations decreased the ratio of successfully learned males (but not females). The observed effects were not associated with changes in locomotor activity.

  14. The effects of the perinatal treatment with 5-hydroxytryptophan or tranylcypromine on the peripheral and central serotonin homeostasis in adult rats.

    PubMed

    Hranilovic, Dubravka; Blazevic, Sofia; Ivica, Nedjeljka; Cicin-Sain, Lipa; Oreskovic, Darko

    2011-08-01

    Serotonin (5HT) is a biologically active amine present in mammals in the brain and the peripheral tissues. Autism is a neurodevelopmental disorder in which 5HT homeostasis is disturbed both centrally and peripherally, but the relationship between the 5HT disturbances in the two compartments is not understood. In an attempt to explore the relationship between the disturbed peripheral 5HT homeostasis and central 5HT functioning, we exposed the developing rat brain to increased 5HT concentrations, by treatment of rats with subcutaneous injections of the immediate 5HT precursor 5-hydroxy-L-tryptophan (5HTP, 25 mg/kg), or the non-selective MAO inhibitor tranylcypromine (TCP, 2 mg/kg), during the period of the most intensive development of 5HT neurons--from gestational day 13 to post-natal day 21. The effects of the mentioned treatments on peripheral and central 5HT levels were then studied in adult rats. Platelet and plasma 5HT concentrations (measured by ELISA), as well as cortical and midbrain 5HT, tryptophan and 5-hydroxyindoleacetic acid levels (measured by HPLC) were determined in twelve 5HTP treated and eight TCP treated rats, and compared with the values measured in 10 control, saline treated rats. Treatment with 5HTP significantly raised peripheral but not central 5HT concentrations. At adult age, peripheral 5HT homeostasis was re-established, while modest decrease in 5HT concentration was observed in frontal cortex, presumably due to hyperserotonemia-induced loss of 5HT terminals during brain development. Treatment with TCP induced significant 5HT elevations in both compartments. At adult age, permanent changes in 5HT homeostasis were observed, both peripherally (as hyperserotonemia) and centrally (as altered 5HT metabolism with decreased 5HT concentrations). Further studies are planned in order to explore the nature of the different disturbances of 5HT homeostasis induced by the two compounds, and their results are expected to shed some light on the role of

  15. The Effects of Partial Mechanical Loading and Ibandronate on Skeletal Tissues in the Adult Rat Hindquarter Suspension Model for Microgravity

    NASA Technical Reports Server (NTRS)

    Schultheis, Lester W.

    1999-01-01

    We report initial data from a suspended rat model that quantitatively relates chronic partial weightbearing to bone loss. Chronic partial weightbearing is our simulation of the effect of limited artificial gravity aboard spacecraft or reduced planetary gravity. Preliminary analysis of bone by PQCT, histomorphometry, mechanical testing and biochemistry suggest that chronic exposure to half of Earth gravity is insufficient to prevent severe bone loss. The effect of episodic full weightbearing activity (Earth Gravity) on rats otherwise at 50% weightbearing was also explored. This has similarity to treatment by an Earth G-rated centrifuge on a spacecraft that normally maintained artificial gravity at half of Earth G. Our preliminary evidence, using the above techniques to analyze bone, indicate that 2 hours daily of full weightbearing was insufficient to prevent the bone loss observed in 50% weightbearing animals. The effectiveness of partial weightbearing and episodic full weightbearing as potential countermeasures to bone loss in spaceflight was compared with treatment by ibandronate. Ibandronate, a long-acting potent bisphosphonate proved more effective in preventing bone loss and associated functionality based upon structure than our first efforts at mechanical countermeasures. The effectiveness of ibandronate was notable by each of the testing methods we used to study bone from gross structure and strength to tissue and biochemistry. These results appear to be independent of generalized systemic stress imposed by the suspension paradigm. Preliminary evidence does not suggest that blood levels of vitamin D were affected by our countermeasures. Despite the modest theraputic benefit of mechanical countermeasures of partial weightbearing and episodic full weightbearing, we know that some appropriate mechanical signal maintains bone mass in Earth gravity. Moreover, the only mechanism that correctly assigns bone mass and strength to oppose regionally specific force

  16. The Effects of Partial Mechanical Loading and Ibandronate on Skeletal Tissues in the Adult Rat Hindquarter Suspension Model for Microgravity

    NASA Technical Reports Server (NTRS)

    Schultheis, Lester W.

    1999-01-01

    We report initial data from a suspended rat model that quantitatively relates chronic partial weightbearing to bone loss. Chronic partial weightbearing is our simulation of the effect of limited artificial gravity aboard spacecraft or reduced planetary gravity. Preliminary analysis of bone by PQCT, histomorphometry, mechanical testing and biochemistry suggest that chronic exposure to half of Earth gravity is insufficient to prevent severe bone loss. The effect of episodic full weightbearing activity (Earth Gravity) on rats otherwise at 50% weightbearing was also explored. This has similarity to treatment by an Earth G-rated centrifuge on a spacecraft that normally maintained artificial gravity at half of Earth G. Our preliminary evidence, using the above techniques to analyze bone, indicate that 2 hours daily of full weightbearing was insufficient to prevent the bone loss observed in 50% weightbearing animals. The effectiveness of partial weightbearing and episodic full weightbearing as potential countermeasures to bone loss in spaceflight was compared with treatment by ibandronate. Ibandronate, a long-acting potent bisphosphonate proved more effective in preventing bone loss and associated functionality based upon structure than our first efforts at mechanical countermeasures. The effectiveness of ibandronate was notable by each of the testing methods we used to study bone from gross structure and strength to tissue and biochemistry. These results appear to be independent of generalized systemic stress imposed by the suspension paradigm. Preliminary evidence does not suggest that blood levels of vitamin D were affected by our countermeasures. Despite the modest theraputic benefit of mechanical countermeasures of partial weightbearing and episodic full weightbearing, we know that some appropriate mechanical signal maintains bone mass in Earth gravity. Moreover, the only mechanism that correctly assigns bone mass and strength to oppose regionally specific force

  17. Effects of 2,4-dichlorophenoxyacetic acid on the ventral prostate of rats during the peri-pubertal, pubertal and adult stage.

    PubMed

    Pochettino, Arístides A; Hapon, María Belén; Biolatto, Silvana M; Madariaga, María José; Jahn, Graciela A; Konjuh, Cintia N

    2016-10-01

    The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is used on a wide variety of terrestrial and aquatic broadleaf weeds. 2,4-D has been shown to produce a wide range of adverse effects on animal and human health. The aim of the current study was to evaluate the effects of pre- and postnatal exposure to 2,4-D on rat ventral prostate (VP). Pregnant rats were exposed daily to oral doses of 70 mg/kg/day of 2,4-D from 16 days of gestation up to 23 days after delivery. Then, the treated groups (n = 8) were fed with a 2,4-D added diet until sacrificed by decapitation on postnatal day (PND) 45, 60, or 90. Morphometric studies were performed and androgen receptor (AR) protein levels in the VP were determined. AR, insulin-like growth factor-I (IGF-1) and insulin-like growth factor-I receptor (IGF-1R) mRNA expression in the VP along with testosterone (T), dihydroxytestosterone (DHT), growth hormone (GH) and IGF-1 serum levels were also determined to ascertain whether these parameters were differentially affected. Results of this study showed that 2,4-D exposure during gestation and until adulthood altered development of the prostate gland in male rats, delaying it at early ages while increasing its size in adults, indicate that 2,4-D could behave as endocrine disruptors (EDs).

  18. Effects of bilateral efferent duct ligation on sperm motility and secretion of FSH, LH, inhibin, and testosterone in adult male rats.

    PubMed

    Ren, Longquan; Medan, Mohamed S; Li, Chunmei; Weng, Qiang; Kawaguchi, Maiko; Watanabe, Gen; Taya, Kazuyoshi

    2006-10-01

    Effects of bilateral efferent duct ligation (EDL) on sperm motility and testicular endocrinology were investigated in adult male rats. Bilateral EDL was created surgically in adult male rats (EDL group) and shamoperated rats were used as control (control group). Five rats from each group were killed on d 3, 5, 7, 14, and 35 after the surgery. The sperm motility parameters were determined by a computer-assisted sperm analysis system using sperm collected from the cauda epididymis. Concentrations of spermatozoa in epididymis and testis were counted. The motility of sperm decreased remarkably in EDL rats compared with controls on 5 d after the operation. Four sperm motility parameters-straight velocity (VSL), deviation of the sperm head from the mean trajectory (ALH, mean), the maximum amplitude of lateral head displacement (ALH, max) and curvilinear velocity (VCL)-increased on 3 d after the operation, and followed by a subsequent decline 5 and 7 d later. Concentrations of sperm significantly decreased in both testes and epididymis from 3 and 5 d after the operation. Plasma concentrations of FSH and LH increased significantly in EDL rats from 5 and 7 d after the operation, whereas plasma concentrations of immunoreactive (ir)-inhibin, inhibin B, and testosterone decreased. Testicular content of irinhibin showed an initial increase on 3 d after the operation, followed by a subsequent decline to levels significantly below controls by d 7 postoperation. On the other hand, testicular contents of testosterone were significantly higher in the EDL group than the control group on d 7-35 after the operation, whereas circulating levels of testosterone remained low. In the EDL testes, marked degenerative changes in the Sertoli cells and spermatogonia were observed, whereas Leydig cells showed clear hyperplasia. These results demonstrated that bilateral EDL induced a rapid reduction of sperm motility parameters during a short time. Present results also suggest that EDL first

  19. Effects of acute microinjections of thyroid hormone to the preoptic region of hypothyroid adult male rats on sleep, motor activity and body temperature.

    PubMed

    Moffett, Steven X; Giannopoulos, Phillip F; James, Thomas D; Martin, Joseph V

    2013-06-21

    Thyroid hormones induce short-latency nongenomic effects in adult brain tissue, suggesting that their acute administration would affect brain activity in intact animals. The influence on EEG-defined sleep of acute restoration of l-3,3'5-triiodothyronine (T3) to a sleep-regulatory brain region, the preoptic region, was examined in hypothyroid rats. Sleep parameters were monitored for 48 h weekly: for 24 h immediately following a control microinjection and for an additional 24h after a second microinjection including a T3 dose to the preoptic region or lateral ventricle. Male albino rats were implanted with EEG and EMG electrodes, abdominal temperature/activity transponders and unilateral lateral ventricle cannulae or bilateral preoptic region cannulae, and were given 0.02% n-propythiouracil (PTU) in their drinking water for 4 weeks. For histologically-confirmed bilateral preoptic region cannula placements (N=7), effects of T3 (especially a 3 μg dose) were apparent within 10h of injection as decreases in REM, NREM and total sleep and increases in waking and activity. Minimal effects of lateral ventricle T3 microinjection were demonstrated (N=5). Significant effects due to the time of day on the experimental measures were seen in both lateral ventricle and preoptic region groups, but these effects did not interact with the effect of administered hormone dose. These effects of T3 microinjection to the preoptic region were demonstrated after acute injections and within hours of injection rather than after chronic administration over days.

  20. Ontogenetic noradrenergic lesion alters histaminergic activity in adult rats.

    PubMed

    Nowak, Przemyslaw; Jochem, Jerzy; Zwirska-Korczala, Krystyna; Josko, Jadwiga; Noras, Lukasz; Kostrzewa, Richard M; Brus, Ryszard

    2008-04-01

    To determine whether noradrenergic nerves might have a modulatory role on the sensitivity or reactivity of histaminergic receptor systems in brain, behavioral effects of the respective histamine H1, H2 and H3 antagonists S(+)chlorpheniramine, cimetidine and thioperimide in control adult rats were compared to the effects in adult rats that had been lesioned as neonates with the noradrenergic neurotoxin DSP-4. On the 1st and 3rd days after birth rat pups were treated with either saline or DSP-4 (50 mg/kg sc), then returned to their home cages with the dam. At 8 weeks when rats were tested, S(+)chlorpheniramine (10 mg/kg ip) was found to increase locomotor activity in intact and DSP-4 lesioned rats, while cimetidine (5 mg/kg, ip) and thioperimide (5 mg/kg, ip) increased activity several-fold solely in the DSP-4 group. Exploratory activity, nociceptive activity, and irritability were little altered by the histamine antagonists, although oral activity was increased by thioperimide in intact and lesioned rats, and by cimetidine or S(+)chlorpheniramine in DSP-4 rats. High performance liquid chromatography with electrochemical detection was used to determine that DSP-4 produced a 90% reduction in frontal cortex, hippocampus and hypothalamus, with a 90% elevation of NE in cerebellum--reflecting reactive sprouting of noradrenergic fibers consequent to lesion of noradrenergic tracts projecting to proximal brain regions. These findings indicate that perinatal noradrenergic fiber lesioning in rat brain is associated with an altered behavioral spectrum by histamine H1, H2 and H3 receptor antagonists, thereby implicating histaminergic systems as modulators of noradrenergic systems in brain.

  1. Enteric-formulated lactoferrin was more effectively transported into blood circulation from gastrointestinal tract in adult rats.

    PubMed

    Takeuchi, Takashi; Jyonotsuka, Takahiro; Kamemori, Nao; Kawano, Genji; Shimizu, Hirohiko; Ando, Kunio; Harada, Etsumori

    2006-11-01

    We have previously demonstrated that intestinally infused bovine lactoferrin (bLF) is transported into the blood circulation via the lymphatic pathway, not via the portal circulation. Therefore, in the present study, we further investigated whether intragastrically infused enteric-formulated bLF (EF-bLF) was more efficiently absorbed than bLF from the intestine in adult rats. The rats were randomly divided into three groups: 30 and 300 mg kg(-1) non-enteric-formulated bLF (non-EF-bLF) groups and a 30 mg kg(-1) EF-bLF group. Thoracic lymph was collected from a thoracic lymph duct under general anaesthesia. Bovine lactoferrin was infused into the stomach or duodenal lumen via a needle for a period of over 1 min in a volume of 1 ml kg(-1). The bLF transported into the lymph was assayed quantitatively by double-antibody enzyme-linked immunosorbent assay (ELISA). Following the intragastric administration of bLF, the three groups showed almost the same lymph flow, but the bLF concentration in the lymph fluid in the EF-bLF group increased significantly and peaked 3 h after administration. With intraduodenal administration, the bLF concentration in the lymph fluid of the higher non-EF-bLF group was significantly higher than those of the other groups. The amount of absorbed bLF in the EF-bLF group was, however, about 10 times higher than that in the lower non-EF-bLF group, when it was administered intragastrically. These data show that enteric-formulated bLF is less susceptible to gastric pepsin and is more efficiently absorbed from the intestine than is non-enteric-formulated bLF.

  2. The effects of nicotine self-administration and withdrawal on concurrently available chow and sucrose intake in adult male rats

    PubMed Central

    Bunney, Patricia E.; Burroughs, Danielle; Hernandez, Christine; LeSage, Mark G

    2016-01-01

    Carbohydrate intake, preference, and taste thresholds may be altered in current and former cigarette smokers, which may mediate weight gain and risk for obesity in individuals who quit smoking. Attempts to model these effects in rodents have primarily used noncontingent nicotine administration. The purpose of this research was to characterize changes in chow and sucrose intake in rats during a 23-h access model of i.v. nicotine self-administration (NSA), in which rats lever-pressed for chow, sucrose, and nicotine under concurrent fixed-ratio (FR) 1 schedules. Male rats were assigned to one of three groups that differed in food and drug availability. The Nicotine C+S group had concurrent access to nicotine, chow, and sucrose. The Saline C+S group had access to saline, chow, and sucrose. The Nicotine C-Only group had access to nicotine and chow, but not sucrose. Changes in food intake and weight gain were assessed during baseline, NSA, and nicotine withdrawal (i.e., saline extinction). Weight gain was significantly slowed during NSA and increased during withdrawal, but did not differ between the nicotine groups. NSA produced a significant decrease in both chow and sucrose intake. Gradual tolerance to nicotine’s effects on sucrose, but not chow intake, occurred. During withdrawal, chow and sucrose intake increased, with a larger percent increase in sucrose intake compared to chow. The proportion of total food intake from sucrose was greater at the end of withdrawal compared to baseline, indicating a history of nicotine intake changed dietary preference. Combined, these results indicate that sucrose intake is more resistant to nicotine’s appetite suppressant effects and withdrawal from nicotine produces a greater increase in sweet food intake alongside general increases in chow intake. Changes in overall food intake in current and ex-smokers may lead to increased risk for obesity and other health problems, potentially limiting the benefit of quitting smoking. PMID

  3. The effects of nicotine self-administration and withdrawal on concurrently available chow and sucrose intake in adult male rats.

    PubMed

    Bunney, Patricia E; Burroughs, Danielle; Hernandez, Christine; LeSage, Mark G

    2016-02-01

    Carbohydrate intake, preference, and taste thresholds may be altered in current and former cigarette smokers, which may mediate weight gain and risk for obesity in individuals who quit smoking. Attempts to model these effects in rodents have primarily used noncontingent nicotine administration. The purpose of this research was to characterize changes in chow and sucrose intake in rats during a 23-h access model of i.v. nicotine self-administration (NSA), in which rats lever-pressed for chow, sucrose, and nicotine under concurrent fixed-ratio (FR) 1 schedules. Male rats were assigned to one of three groups that differed in food and drug availability. The Nicotine C+S group had concurrent access to nicotine, chow, and sucrose. The Saline C+S group had access to saline, chow, and sucrose. The Nicotine C-Only group had access to nicotine and chow, but not sucrose. Changes in food intake and weight gain were assessed during baseline, NSA, and nicotine withdrawal (i.e., saline extinction). Weight gain was significantly slowed during NSA and increased during withdrawal, but did not differ between the nicotine groups. NSA produced a significant decrease in both chow and sucrose intake. Gradual tolerance to nicotine's effects on sucrose, but not chow intake, occurred. During withdrawal, chow and sucrose intake increased, with a larger percent increase in sucrose intake compared to chow. The proportion of total food intake from sucrose was greater at the end of withdrawal compared to baseline, indicating a history of nicotine intake changed dietary preference. Combined, these results indicate that sucrose intake is more resistant to nicotine's appetite suppressant effects and withdrawal from nicotine produces a greater increase in sweet food intake alongside general increases in chow intake. Changes in overall food intake in current and ex-smokers may lead to increased risk for obesity and other health problems, potentially limiting the benefit of quitting smoking. Copyright

  4. Neuroprotective effect of the alpha 7 nicotinic receptor agonist PHA 543613 in an in vivo excitotoxic adult rat model.

    PubMed

    Foucault-Fruchard, Laura; Doméné, Aurélie; Page, Guylène; Windsor, Marguerite; Emond, Patrick; Rodrigues, Nuno; Dollé, Frédéric; Damont, Annelaure; Buron, Frédéric; Routier, Sylvain; Chalon, Sylvie; Antier, Daniel

    2017-07-25

    Neuroinflammation is a key component of the pathophysiology of neurodegenerative diseases. The link between nicotine intake and positive outcome has been established, suggesting a role played by nicotinic receptors (nAChRs), especially α7nAChRs. The objective of this study was to evaluate the potential dose effects of PHA 543613 on neuron survival and striatal microglial activation in a rat model of brain excitotoxicity. A preliminary study was performed in vitro to confirm PHA 543613 agonist properties on α7nAChRs. Rats were lesioned in the right striatum with quinolinic acid (QA) and received either vehicle or PHA 543613 at 6 or 12mg/kg twice a day until sacrifice at Day 4 post-lesion. We first compared the translocator protein quantitative autoradiography in QA-lesioned brains with [(3)H]DPA-714 and [(3)H]PK-11195. The effects of PHA 543613 on microglial activation and neuronal survival were then evaluated through [(3)H]DPA-714 binding and immunofluorescence staining (Ox-42, NeuN) on adjacent brain sections. We demonstrated that [(3)H]DPA-714 provides a better signal-to-noise ratio than [(3)H]PK-11195. Furthermore, we showed that repeated PHA 543613 administration at a dose of 12mg/kg to QA-lesioned rats significantly protected neurons and reduced the intensity of microglial activation. This study reinforces the hypothesis that α7nAChR agonists can provide beneficial effects in the treatment of neurodegenerative diseases through potential modulation of microglial activation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Protective effect of combined pumpkin seed and ginger extracts on sperm characteristics, biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide.

    PubMed

    Aghaie, Somaieh; Nikzad, Hossein; Mahabadi, Javad Amini; Taghizadeh, Mohsen; Azami-Tameh, Abolfazl; Taherian, Aliakbar; Sajjadian, Seyyed Mohammad Sajjad; Kamani, Mehran

    2016-09-01

    Reproductive toxicity is one of the side effects of cyclophosphamide (CP) in cancer treatment. Pumpkin seeds and Zingiber officinale are natural sources of antioxidants. We investigated the possible protective effect of combined pumpkin seed and Zingiber officinale extracts on sperm characteristics, epididymal histology and biochemical parameters of CP-treated rats. Male adult Wistar rats were divided randomly into six groups. Group 1, as a control, received an isotonic saline solution injection intraperitoneally (IP). Group 2 were injected IP with a single dose of CP (100 mg/kg) once. Groups 3 and 4 received CP plus 300 and 600 mg/kg combined pumpkin seed and Zingiber officinale extract (50:50). Groups 5 and 6 received only 300 and 600 mg/kg combined pumpkin seed and Zingiber officinale extract. Six weeks after treatment, sperm characteristics, histopathological changes and biochemical parameters were assessed. In CP-treated rats, motile spermatozoa were decreased, and abnormal or dead spermatozoa increased significantly (P < 0.001) but administration of the mixed extract improved sperm parameters. Epididymal epithelium and fibromascular thickness were also improved in extract-treated rats compared to control or CP groups. Biochemical analysis showed that the administration of combined extracts could increase the total antioxidant capacity (TAC) level significantly in groups 3, 4, 5 and 6. Interestingly, the mixed extract could decrease most of the side effects of CP such as vacuolization and separation of epididymal tissue. Our findings indicated that the combined extracts might be used as a protective agent against CP-induced reproductive toxicity.

  6. Combined neonatal stress and young-adult glucocorticoid stimulation in rats reduce BDNF expression in hippocampus: effects on learning and memory.

    PubMed

    Choy, Kwok Ho Christopher; de Visser, Yvonne; Nichols, Nancy R; van den Buuse, Maarten

    2008-01-01

    Epidemiological studies suggest that multiple developmental disruptions are involved in the etiology of psychiatric illnesses including schizophrenia. In addition, altered expression of brain-derived neurotrophic factor (BDNF) has been implicated in these illnesses. In the present study, we examined the combined long-term effect of an early stress, in the form of maternal deprivation, and a later stress, simulated by chronic young-adult treatment with the stress hormone, corticosterone, on BDNF expression in the hippocampus of rats. To assess whether there were behavioral effects, which may correlate with the BDNF changes, learning and memory was tested in the Y-maze test for short term spatial memory, the Morris water maze for long-term spatial memory, and the T-maze test for working memory. Four groups of rats received either no stress, maternal deprivation, corticosterone treatment, or both. Dorsal hippocampus sections obtained from parallel groups were used for BDNF mRNA in situ hybridization. Rats which had undergone both maternal deprivation and corticosterone treatment displayed a unique and significant 25-35% reduction of BDNF expression in the dentate gyrus (DG), and similar trends in the CA1 and CA3 regions of the hippocampus. These "two-hit" animals exhibited a learning delay in the Morris water maze test, a marked deficit in the Y-maze, but little change in the T-maze test. However, some aspects of cognition were also altered in rats with either maternal deprivation or corticosterone treatment. This study demonstrates a persistent effect of two developmental disruptions on BDNF expression in the hippocampus, with parallel, but not completely correlative changes in learning and memory.

  7. Effect of vitamin A deficiency on permeability of the small intestinal mucosa for macromolecules in adult rats

    SciTech Connect

    Gmoshinskii, I.V.; Khvylya, S.I.; Kon', I.Ya.

    1987-07-01

    The authors study the effect of experimental vitamin A deficiency on absorption of macromolecules of hen's ovalbumin in the intestine. An electron-microscopic study of permeability of small intestine enterocytes for particles of colloidal lanthanum hydroxide La(OH)/sub 3/ was carried out at the same time. The concentration of unsplit hen's ovalbumin in the blood of the rats used in the experiment was determined by competitive radioimmunoassay. Samples of serum were incubated with indicator doses of /sup 125/I-OA. Radioactivity of the precipitates was measured.

  8. Physiological effects of long-term feeding diets supplemented with potato fibre or cellulose to adult rats.

    PubMed

    Pastuszewska, Barbara; Taciak, Marcin; Tuśnio, Anna; Misztal, Tomasz; Ochtabińska, Anna

    2010-04-01

    Nutritional value of diets containing 10% potato fibre or cellulose (diets MPF and MC, respectively) and their long-term effects on parameters related to potential health benefits were studied in rats. In a first experiment nutrient digestibility and metabolisable energy of the diets were determined. In a second experiment, each diet was fed to 20 male and 20 female rats aged nine weeks old during 12 (Lot W12) or 24 (Lot W24) weeks. Feed intakes per cage and body weight of rats were registered. In all animals organ weight was determined and in animals of Lot W12 and in males of Lot W24 biochemical blood parameters were analysed. In males of Lot W24, caecal SCFA concentration and body composition were also determined. Testosterone blood concentration was determined in males of Lots W12 and W24. Protein and fat digestibilities were lower, while those of ash, crude fibre and NFE were higher in the MPF than the MC diet. The energy value of the MPF diet was greater but energy intake was similar for both diets. Body weight, body protein and fat contents in males of Lot W24 did not differ between the groups, while body ash was significantly greater in MPF than MC rats (2.64 vs. 2.17 g/100 g BW). SCFA concentration and pool were considerably greater in MPF than MC rats, the SCFA profile being similar. Potato fibre did not affect total cholesterol, whereas it decreased triglycerides and very low density lipoproteins (VLDL) in Lot W12 of both genders, and tended to decrease them in males of Lot W24. Blood glucose and testosterone concentrations and relative mass of prostate were significantly depressed by the MPF diet in males of Lot W24. It can be concluded that feeding potato fibre stimulates caecal fermentation, improves mineral absorption and does not affect total cholesterol levels. The concentration of lipids, VLDL, glucose and testosterone depended on potato fibre in an age-dependent way.

  9. Effects of chronic dietary exposure to monosodium glutamate on feeding behavior, adiposity, gastrointestinal motility, and cardiovascular function in healthy adult rats.

    PubMed

    López-Miranda, V; Soto-Montenegro, M L; Uranga-Ocio, J A; Vera, G; Herradón, E; González, C; Blas, C; Martínez-Villaluenga, M; López-Pérez, A E; Desco, M; Abalo, R

    2015-11-01

    Monosodium glutamate (MSG) is a flavor-enhancer widely used as a food additive. However, its safe dietary concentration and its toxicity, including its possible implication in the recent metabolic syndrome pandemia, is still a controversial issue. Therefore, a deep knowledge of its effects upon regular dietary use is needed. Our aim was to evaluate the effects of chronic exposure to MSG on feeding behavior, abdominal fat, gastrointestinal motility, and cardiovascular function in rats. Two groups of adult male Wistar rats were used: control and treated with MSG (4 g/L in drinking water) for 6 weeks. Different functional parameters were determined and the histological structure was analyzed in tissues of interest. Compared to control animals, chronic MSG increased water intake but did not modify food ingestion or body weight gain. Neither the abdominal fat volume nor the fat fraction, measured by magnetic resonance imaging, was modified by MSG. Monosodium glutamate did not alter general gastrointestinal motility, but significantly increased the colonic response to mechanical stimulation. It slightly reduced endothelium-dependent relaxation in aorta, without significantly modifying any other cardiovascular parameters. No significant histological alterations were detected in salivary glands, intestinal wall, aorta, heart, and kidney. Chronic treatment with MSG in the adult rat increased water intake. This supports its potential to improve acceptance of low-fat regimens and to increase hydration in the elderly and sportspeople, often at risk of dehydration. Changes in colonic contractility and cardiovascular function could have some long-term repercussions warranting further research. © 2015 John Wiley & Sons Ltd.

  10. L-Dopa effect on frequency-dependent depression of the H-reflex in adult rats with complete spinal cord transection.

    PubMed

    Liu, Hao; Skinner, Robert D; Arfaj, Ahmad; Yates, Charlotte; Reese, Nancy B; Williams, Keith; Garcia-Rill, Edgar

    2010-10-30

    This study investigated whether l-dopa (DOPA), locomotor-like passive exercise (Ex) using a motorized bicycle exercise trainer (MBET), or their combination in adult rats with complete spinal cord transection (Tx) preserves and restores low frequency-dependent depression (FDD) of the H-reflex. Adult Sprague-Dawley rats (n=56) transected at T8-9 had one of five treatments beginning 7 days after transection: Tx (transection only), Tx+Ex, Tx+DOPA, Tx+Ex+DOPA, and control (Ctl, no treatment) groups. After 30 days of treatment, FDD of the H-reflex was tested. Stimulation of the tibial nerve at 0.2, 1, 5, and 10Hz evoked an H-reflex that was recorded from plantar muscles of the hind paw. No significant differences were found at the stimulation rate of 1Hz. However, at 5Hz, FDD of the H-reflex in the Tx+Ex, Tx+DOPA and Ctl groups was significantly different from the Tx group (p<0.01). At 10Hz, all of the treatment groups were significantly different from the Tx group (p<0.01). No significant difference was identified between the Ctl and any of the treatment groups. These results suggest that DOPA significantly preserved and restored FDD after transection as effectively as exercise alone or exercise in combination with DOPA. Thus, there was no additive benefit when DOPA was combined with exercise. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Effects of maternal separation on behavior and brain damage in adult rats exposed to neonatal hypoxia-ischemia.

    PubMed

    Tata, Despina A; Markostamou, Ioanna; Ioannidis, Anestis; Gkioka, Mara; Simeonidou, Constantina; Anogianakis, Georgios; Spandou, Evangelia

    2015-03-01

    Animal studies suggest that maternal separation, a widely used paradigm to study the effects of early life adversity, exerts a profound and life-long impact on both brain and behavior. The aim of the current study was to investigate whether adverse early life experiences interact with neonatal hypoxia-ischemia, affecting the outcome of this neurological insult at both functional and structural levels during adulthood. Rat pups were separated from their mothers during postnatal days 1-6, for either a short (15 min) or prolonged (180 min) period, while another group was left undisturbed. On postnatal day 7, a subgroup from each of the three postnatal manipulations was exposed to a hypoxic-ischemic episode. Behavioral examination took place approximately at three months of age and included tests of learning and memory (Morris water maze, novel object and novel place recognition), as well as motor coordination (rota-rod). We found that both prolonged maternal separation and neonatal hypoxia-ischemia impaired the animals' spatial learning and reference memory. Deficits in spatial but not visual recognition memory were detected only in hypoxic-ischemic rats. Interestingly, prolonged maternal separation prior to neonatal hypoxia-ischemia augmented the reference memory impairments. Histological analysis of infarct size, hippocampal area and thickness of corpus callosum did not reveal any exacerbation of damage in hypoxic-ischemic rats that were maternally separated for a prolonged period. These are the first data suggesting that an adverse postnatal environmental manipulation of just 6 days causes long-term effects on spatial learning and memory and may render the organism more vulnerable to a subsequent insult.

  12. Cardiovascular and renal effects of a collagen cross-link breaker (ALT 711) in adult and aged spontaneously hypertensive rats.

    PubMed

    Susic, Dinko; Varagic, Jasmina; Ahn, Jwari; Frohlich, Edward D

    2004-04-01

    Increased formation of advanced glycosylation end-products on body proteins is a consequence of aging and leads to exaggerated collagen cross-linking eventually increasing cardiovascular stiffness. This study reports our initial inquires into the cardiovascular and renal effects of a cross-link breaker (ALT-711) in aged spontaneously hypertensive rats (SHR). The first experiment, in 45-week-old SHR, showed that (among four doses) the dose of 1 mg/kg/d of ALT-711 given for 4 months was most effective in reducing left ventricular and aortic mass indexes. ALT-711 also reduced left ventricular hydroxyproline concentration (5.8 +/- 0.2 v 5.1 +/- 0.3 mg/g in controls, P < .05); however, it did not affect systemic or regional hemodynamics. In older SHR, ALT-711 (1 mg/kg/d) reduced (P < .05) systolic pressure (tail-cuff) (from 203 +/- 3 mm Hg at outset to 187 +/- 3 mm Hg at 8 weeks). Systolic pressure remained unchanged in placebo-treated rats. In addition, left ventricular index (3.09 +/- 0.10 v 3.44 +/- 0.05 mg/g) and aortic mass index (1.54 +/- 0.04 v 1.74 +/- 0.05 mg/mm) were reduced by ALT-711. In the third experiment, 1-year-old SHR were given vehicle or ALT-711 (1 mg/kg/d) or placebo until natural death. After 3 months, ALT-711 markedly reduced urinary protein excretion (74.5 +/- 8.6 v 135.4 +/- 11.8 mg/24 h). Echocardiographic studies, performed at the outset and after 3 and 6 months, revealed two changed indexes. Left ventricular end-diastolic diameter increased more in control than in ALT rats, whereas E-wave deceleration time decreased more in control than in ALT rats. Therapy with ALT-711 exerted beneficial cardiovascular and renal effects in aged SHR, improving systolic pressure, left ventricular mass, geometry, and hydroxyproline content while reducing urinary protein excretion.

  13. Effect of neonatal beta-endorphin imprinting on sexual behavior and brain serotonin level in adult rats.

    PubMed

    Csaba, G; Knippel, Barbara; Karabélyos, Cs; Inczefi-Gonda, Agnes; Hantos, Monika; Tóthfalusi, L; Tekes, Kornélia

    2003-05-23

    A single dose (3 microg) beta-endorphin was administered to newborn female and male rats (hormonal imprinting). In adult age (at 5 months) sexual behavior, steroid hormone binding capacity and brain serotonin content was studied. Females' sexual activity (lordosis quotient) significantly decreased and more animals protested against mounting (ratio of kicking and crying 21/24 vs. 8/24; p < 0.001). Males' sexual activity did not change, however more males were aggressive (4/10 vs. 1/10). Uterine estrogen receptor density significantly increased and affinity decreased. There was no change in the binding capacity of thymic glucocorticoid receptors. In the brain, five regions were studied for serotonin content. There was a gender difference in serotonin level and the intragroup differences were also high. In the endorphin treated males the serotonin level was significantly lower than in the controls. In the endorphin treated females the intragroup scattering has been significantly reduced. Nociceptin content of the cerebrospinal fluid was not changed. The experiments call attention to the possibility of adjustment of sexual and behavioral sphere by the individually different endorphin surge during labor.

  14. Effects of long-term sensory deprivation on asymmetric synapses in the whisker barrel field of the adult rat.

    PubMed

    Machín, Raquel; Pérez-Cejuela, César G; Bjugn, Roger; Avendaño, Carlos

    2006-08-30

    Whisker trimming deprives the cortical barrel field from the patterned sensory input that derives from active touch but leaves passive tactile signals unaltered. We have studied in the rat barrel field, by stereological procedures, the effects of a sustained period of unilateral deprivation by whisker clipping during adolescence and early adulthood on (1) the surface density (SV) of asymmetric synapses, as determined from measuring the presynaptic membrane specializations, and (2) the numerical density of asymmetric synaptic profiles (NA), classified according to their postsynaptic target and their apparent curvature. Compared to control rats, the procedure did not change the overall volume of the region, the volume fraction occupied by each cortical layer, or the volume fraction occupied by unmyelinated axons and boutons. However, the deprived barrel cortex displayed an increase in SV in layers I and II, and an increase in NA in layer I and in the cortex as a whole, mainly due to an increase in profiles with a convex shape. Layer IV was the least affected by the deprivation. These results point to a net increase, rather than a decrease, of excitatory synapses in the deprived cortex, which could result from a deprivation-induced decrease in the rate of normal synapse loss. This effect occurs specifically in superficial layers, more involved in intracortical and cortico-cortical, rather than thalamo-cortical, processing.

  15. Long-term effect of morphine administration in young rats on the analgesic opioid response in adult life.

    PubMed

    Rozisky, Joanna Ripoll; Dantas, Giovana; Adachi, Lauren Spezia; Alves, Viviane Soares; Ferreira, Maria Beatriz Cardoso; Sarkis, João José Freitas; Torres, Iraci Lucena Da Silva

    2008-10-01

    Neonates, infants and children are often exposed to pain from invasive procedures during intensive care and during the post-operative period. Opioid anesthesia and post-operative opioid analgesia have been used in infants and result in clinical benefits. The objectives of this study were to verify the effect of repeated 5 microg morphine administration (subcutaneous), once a day for 7 days in 8-day-old rats, at P8 until P14. To verify the long-term effect of morphine, the animals were submitted to a second exposure of 5mg/kg (intraperitoneal) of morphine at P80 until P86. Animals that received morphine for 7 days, at P14 did not develop tolerance, however at P80, rats demonstrated greater morphine analgesia. At P86, after 7 days of morphine administration, animals showed classical tolerance. These findings may have important implications for the human neonate, suggesting a possible explanation for the differences in the requirements of morphine observed in the youngest patients.

  16. The effects of a ketogenic diet on behavioral outcome after controlled cortical impact injury in the juvenile and adult rat.

    PubMed

    Appelberg, K Sofia; Hovda, David A; Prins, Mayumi L

    2009-04-01

    The ketogenic diet has been shown to have unique properties that make it a more suitable cerebral fuel under various neuropathological conditions (e.g., starvation, ischemia, and traumatic brain injury (TBI). Recently, age-dependent ketogenic neuroprotection was shown among postnatal day 35 (PND35) and PND45 rats after TBI, but not in PND17 and PND65 animals (Prins et al., 2005). The present study addresses the therapeutic potential of a ketogenic diet on motor and cognitive deficits after TBI. PND35 and PND75 rats received sham or controlled cortical impact (CCI) surgery and were placed on either standard (Std) or ketogenic (KG) diet for 7 days. Beam walking and the Morris water maze (MWM) were used to assess sensory motor function and cognition, respectively. PND35 CCI Std animals showed significantly longer traverse times than sham and CCI KG animals at the beginning of motor training. Footslip analysis revealed better performance among the sham and the CCI KG animals compared to the CCI Std group. In the MWM PND35 CCI KG animals showed significantly shorter escape latencies compared to CCI Std-fed animals. During the same time period there was no significant difference between sham animals and CCI KG animals. The therapeutic effect of the ketogenic diet on beam walking and cognitive performance was not observed in PND75 animals. This finding supports our theory about age-dependent utilization and effectiveness of ketones as an alternative fuel after TBI.

  17. The Effects of a Ketogenic Diet on Behavioral Outcome after Controlled Cortical Impact Injury in the Juvenile and Adult Rat

    PubMed Central

    Appelberg, K. Sofia; Hovda, David A.

    2009-01-01

    Abstract The ketogenic diet has been shown to have unique properties that make it a more suitable cerebral fuel under various neuropathological conditions (e.g., starvation, ischemia, and traumatic brain injury (TBI). Recently, age-dependent ketogenic neuroprotection was shown among postnatal day 35 (PND35) and PND45 rats after TBI, but not in PND17 and PND65 animals (Prins et al., 2005). The present study addresses the therapeutic potential of a ketogenic diet on motor and cognitive deficits after TBI. PND35 and PND75 rats received sham or controlled cortical impact (CCI) surgery and were placed on either standard (Std) or ketogenic (KG) diet for 7 days. Beam walking and the Morris water maze (MWM) were used to assess sensory motor function and cognition, respectively. PND35 CCI Std animals showed significantly longer traverse times than sham and CCI KG animals at the beginning of motor training. Footslip analysis revealed better performance among the sham and the CCI KG animals compared to the CCI Std group. In the MWM PND35 CCI KG animals showed significantly shorter escape latencies compared to CCI Std-fed animals. During the same time period there was no significant difference between sham animals and CCI KG animals. The therapeutic effect of the ketogenic diet on beam walking and cognitive performance was not observed in PND75 animals. This finding supports our theory about age-dependent utilization and effectiveness of ketones as an alternative fuel after TBI. PMID:19231995

  18. Metabolic and Testicular Effects of the Long-Term Administration of Different High-Fat Diets in Adult Rats

    PubMed Central

    Campos-Silva, Pamella; Furriel, Angelica; Costa, Waldemar S.; Sampaio, Francisco J. B.; Gregório, Bianca M.

    2015-01-01

    ABSTRACT Purpose: To evaluate the effects of different high-fat diets on body mass, carbohydrate metabolism and testicular morphology in rats seven months old. Materials and Methods: Male Wistar rats were divided into four groups: SC (standard chow), HF-S (high fat diet rich in saturated fatty acids), HF-P (high fat diet rich in polyunsaturated fatty acids), HF-SP (high fat diet rich in saturated and polyunsaturated fatty acids). The rats were fed for 16 weeks. Blood samples, testes and genital fat deposits were collected for analysis. Data were analyzed by one-way ANOVA and Bonferroni post hoc test, considering p<0.05 as statistically significant. Results: Different high-fat diets promoted an increase in the body mass (p<0.0001). The genital fat deposits were higher in the high-fat groups (HF-S, HF-P, HF-SP) (p=0.0004). Regarding serum parameters, the animals in the HF-S and HF-SP groups presented hyperglycemia (p=0.0060), hyperinsulinemia (p=0.0030) and hypercholesterolemia (p=0.0021). All of the hyperlipidemic groups showed hyperleptinemia (p=0.0019). Concerning the testis, the HF-S group showed a reduction on the seminiferous epithelium height (p=0.0003) and cell proliferation (p=0.0450). Seminiferous tubule diameter was lower in the HF-SP than in the SC group (p=0.0010). Conclusions: The high fat diet administration, independent of the lipid quality, promotes overweight. Diet rich in saturated fatty acids (lard) alters the carbohydrate metabolism and the testicular morphology with reductions of seminiferous epithelium height, seminiferous tubule diameter and cell proliferation which could be related to a disturbance of spermatogenesis. PMID:26200553

  19. Early nutritional changes induce sexually dimorphic long-term effects on body weight gain and the response to sucrose intake in adult rats.

    PubMed

    Fuente-Martín, Esther; Granado, Miriam; García-Cáceres, Cristina; Sanchez-Garrido, Miguel A; Frago, Laura M; Tena-Sempere, Manuel; Argente, Jesús; Chowen, Julie A

    2012-06-01

    Long-term metabolic effects induced by early nutritional changes are suspected to differ between males and females, but few studies have analyzed both sexes simultaneously. We analyzed the consequences of neonatal nutritional changes on body weight (BW) and the adult response to a sucrose-enriched diet in both male and female rats. Litter size was manipulated at birth to induce over- and undernutrition (4 pups: L4; 12 pups: L12; 20 pups: L20). From 50 to 65 days of age, half of each group received a 33% sucrose solution instead of water. Serum leptin, insulin, and ghrelin levels were analyzed at day 65. At weaning, rats from L4 weighed more and those from L20 weighed less than controls (L12). Body weight was greater in L4 rats throughout the study and increased further compared with controls in adult life. L20 males ate less and gained less weight throughout the study, but L20 females had a significant catch-up in BW. Sucrose intake increased total energy consumption in all groups, but not BW gain, with L4 males and L4 and L20 females reducing weight gain. Yet, sucrose intake increased serum leptin levels, with this increase being significant in L4 and L20 males. Our results suggest that females are more capable than males of recuperating and maintaining a normal BW after reduced neonatal nutrition. Furthermore, increased sucrose intake does not increase BW, but could alter body composition as reflected by leptin levels, with the percentage of calories consumed in the form of sucrose being affected by sex and neonatal nutrition.

  20. Melatonin ameliorates dexamethasone-induced inhibitory effects on the proliferation of cultured progenitor cells obtained from adult rat hippocampus.

    PubMed

    Ekthuwapranee, Kasima; Sotthibundhu, Areechun; Tocharus, Chainarong; Govitrapong, Piyarat

    2015-01-01

    Glucocorticoids, hormones that are released in response to stress, induce neuronal cell damage. The hippocampus is a primary target of glucocorticoids in the brain, the effects of which include the suppression of cell proliferation and diminished neurogenesis in the dentate gyrus. Our previous study found that melatonin, synthesized primarily in the pineal, pretreatment prevented the negative effects of dexamethasone, the glucocorticoid receptor agonist, on behavior and neurogenesis in rat hippocampus. In the present study, we attempted to investigate the interrelationship between melatonin and dexamethasone on the underlying mechanism of neural stem cell proliferation. Addition of dexamethasone to hippocampal progenitor cells from eight-week old rats resulted in a decrease in the number of neurospheres; pretreatment with melatonin precluded these effects. The immunocytochemical analyses indicated a reduction of Ki67 and nestin-positive cells in the dexamethasone-treated group, which was minimized by melatonin pretreatment. A reduction of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation and G1-S phase cell cycle regulators cyclin E and CDK2 in dexamethasone-treated progenitor cells were prevented by pretreatment of melatonin. Moreover, luzindole, a melatonin receptor antagonist blocked the positive effect of melatonin whereas RU48, the glucocorticoid receptor antagonist blocked the negative effect of dexamethasone on the number of neurospheres. Moreover, we also found that dexamethasone increased the glucocorticoid receptor protein but decreased the level of MT1 melatonin receptor, whereas melatonin increased the level of MT1 melatonin receptor but decreased the glucocorticoid receptor protein. These suggest the crosstalk and cross regulation between the melatonin receptor and the glucocorticoid receptor on hippocampal progenitor cell proliferation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Effects of rat odour and shelter on maternal behaviour in C57BL/6 dams and on fear and stress responses in their adult offspring.

    PubMed

    Coutellier, Laurence; Friedrich, Anne-Christin; Failing, Klaus; Marashi, Vera; Würbel, Hanno

    2008-06-09

    Recent studies in rats and mice suggest that developmental plasticity of HPA-stress and fear responses could be mediated by environment-dependent variations in maternal behaviour. The present study was designed to examine this question further by varying the adversity of the maternal environment to study its effects on nest-attendance and maternal care and on the HPA and fear responses in the adult offspring. C57BL/6 dams and their litter were housed in a cage system composed of a nest cage (NC) and a foraging cage (FC) connected by a tunnel. Using a 2 x 2 factorial design, we varied the maternal foraging environment (FC) by the presence or absence of rat odour (feces) and shelters (MouseHouse and tube) from postnatal days 1-14 and assessed the adult offspring's corticosterone response to isolation/novelty stress and their behaviour in three tests of fearfulness (elevated-O-maze, open-field, free exploration). While the presence of shelters in the FC reduced time spent in the NC (nest site attendance), the presence of rat odour in the FC increased active maternal care without altering nest site attendance. Alterations of the offspring's HPA and fear responses were rather subtle. The presence of shelters in the dam's foraging environment decreased fearfulness in the offspring in the free exploration test. In addition, males reared by dams exposed to rat odour were less fearful in the open-field test, and both males and females reared by dams without shelters and rat odour in the FC showed a greater corticosterone response to isolation/novelty stress. Multiple regression analysis indicated a negative relationship between maternal licking/grooming and fearfulness in males and a positive relationship between nest site attendance and fearfulness in females. Taken together, these results indicate that mouse dams adjust specific aspects of maternal behaviour in response to the specific properties of their environment, and that active maternal care and nest site attendance

  2. Safflower (Catharmus tinctorius L.) oil supplementation in overnourished rats during early neonatal development: effects on heart and liver function in the adult.

    PubMed

    Costa, Laís Ribeiro; Macêdo, Patrícia Cavalcanti; de Melo, Janatar Stella Vasconcelos; Freitas, Cristiane Moura; Alves, Aiany Simoes; Barbosa, Humberto de Moura; Lira, Eduardo; Fernandes, Mariana Pinheiro; Batista-de-Oliveira-Hornsby, Manuella; Lagranha, Claudia

    2016-12-01

    Carthamus tinctorius L. (common name: safflower) is an herb whose extracted oil (safflower oil) has been employed in both alternative and conventional medicine in the treatment of disease. Overnutrition during early postnatal life can increase the lifetime risk of obesity and metabolic syndrome. Here we investigate the effect of safflower oil supplementation given during a critical early developmental stage on the eventual occurrence of metabolic disease in overnourished rats. Groups of overnourished or adequately nourished rats were randomly assigned into 2 additional groups for supplementation with either safflower oil (SF) or vehicle for 7 to 30 days. Murinometric data and weights were examined. Serum was collected for measurement of glucose, cholesterol, high-density lipoprotein cholesterol, and triglycerides. Heart and liver oxidative status were also measured. Overnutrition for 7-30 days induced a significant increase in body weight and in values for abdominal circumference, thoracic circumference, body length, and body mass index. SF supplementation did not attenuate the effect of overnutrition on any of these parameters. In addition, overnutrition increased levels of glucose, triglycerides, and very low-density lipid compared with normal controls, but SF supplementation had no effect on these parameters. Measures of oxidative status in heart or liver were not influenced by overnutrition. However, oxidative measures were altered by SF supplementation in both of these organs. The present study reveals that nutritional manipulation during early development induces detrimental effects on metabolism in the adult that are not ameliorated by supplemental SF.

  3. Lasting facilitatory effects of neonatal vibrissae removal on the propagation of cortical spreading depression: an electrophysiological study in well-nourished and early-malnourished adult rats.

    PubMed

    Tenório, Angélica da Silva; Moura, Fábia Rossana da Silva; Silva, Levy Petrus Silvestre de Lima; Guedes, Rubem Carlos Araújo

    2009-12-01

    Early malnutrition interferes with the formation of somatosensory pathways and reduced sensory input activity during brain development can induce morphological and physiological changes in the cerebral cortex, altering their response properties in the long-term. Here, we investigated cortical spreading depression (CSD) propagation in male adult rats submitted to unilateral vibrissae removal, at postnatal days 2-3, and malnourished during lactation followed by nutritional recovery until adulthood (90-120 days), when CSD was recorded. Compared to nutrition-matched non-lesioned controls, CSD-propagation was increased in the hemisphere contralateral to the vibrissae removal. The findings indicate that vibrissae removal during brain development enhances CSD-propagation, and early malnutrition did not modify this effect. Considering that CSD-facilitation persisted until adulthood, we suggest that this effect is permanent. The data might contribute to the understanding of the mechanisms by which sensory input deprivation-induced plasticity modifies cerebral electrophysiological responses in the developing brain.

  4. Effects of acute administration of phentermine, alone or in combination with dexfenfluramine, on pain reactivity in the adult rat.

    PubMed

    Wellman, P J

    2008-09-01

    In the 1990s, phentermine was combined with either fenfluramine or its active enantiomer dexfenfluramine to promote weight loss. Appetite suppressants are known to alter pain reactivity. The current experiment examined the acute impact of phentermine (0, 2.5, 5, 10, or 20 mg/kg) on paw-lick/jump latencies recorded just before and at 10, 20, and 30 min after phentermine injection. In addition, separate groups of rats were treated with 1, 2, or 4 mg/kg dexfenfluramine or with selected combinations of phentermine with dexfenfluramine. Phentermine induced significant analgesia in rats at a dose of 2.5 mg/kg, whereas only the 4.0 mg/kg dose of dexfenfluramine induced significant analgesia. Combinations of 1 mg/kg dexfenfluramine or 2 mg/kg dexfenfluramine with phentermine were mostly additive in terms of changes in analgesia scores. The present results characterize the analgesic action of phentermine, further confirm the analgesic action of dexfenfluramine and suggest an additive analgesic effect for the combination of dexfenfluramine with phentermine.

  5. Ameliorative effect of quercetin against arsenic-induced sperm DNA damage and daily sperm production in adult male rats.

    PubMed

    Jahan, Sarwat; Rehman, Saima; Ullah, Hizb; Munawar, Asma; Ain, Qurat Ul; Iqbal, Tariq

    2016-01-01

    In this study, the protective effect of quercetin was evaluated against arsenic induced reproductive ailments in male rats. For this purpose, male rats (n = 5/group) weighing 180-250 g were used. First group served as control, second group received arsenic (50 ppm) in drinking water. Third group was treated with quercetin (50 mg/kg) alone, while fourth group received arsenic + quercetin. All treatments were carried out for 49 days. After treatment, animals were killed by decapitation; testis and epididymis were dissected out. Right epididymis was minced immediately for comet assay, while left epididymis was processed for histology. Similarly, right testis was homogenized for estimation of daily sperm production (DSP) and detection of metal concentration. The results of our research revealed that arsenic treatment did not cause any significant change in body weight and testicular volume. Quercetin treatment significantly prevented tissue deposition of arsenic within the testis. Arsenic treatment caused a significant reduction in DSP, however, in the arsenic + quercetin-treated group and quercetin alone-treated group, DSP was significantly high as compared to the arsenic-treated group. Histological study of epididymis showed empty lumen in arsenic-treated group while in arsenic + quercetin-treated group and quercetin alone-treated group, lumen were filled with sperm and were comparable to control. Sperm DNA damage, induced by arsenic, was significantly reversed toward control levels by supplementation of quercetin. These results suggest that quercetin not only prevents deposition of arsenic in tissues, but can also protect the sperm DNA damage.

  6. Effect of neural stem cell transplantation combined with erythropoietin injection on axon regeneration in adult rats with transected spinal cord injury.

    PubMed

    Zhao, Y; Zuo, Y; Wang, X L; Huo, H J; Jiang, J M; Yan, H B; Xiao, Y L

    2015-12-22

    We investigated the effect of neural stem cells (NSC) and erythropoietin (EPO) on axon regeneration in adult rats with transected spinal cord injury, and provided an experimental basis for clinical treatment. Forty Wistar rats with T10-transected spinal cord injury were randomly divided into four groups of ten rats: a control group (group A), an NSC-transplant group (group B), an NSC-transplant and EPO group (group C), and an EPO group (group D). Biotinylated dextran amines (BDA) anterograde corticospinal cord neuronal tracing and Fluoro-Gold (FG) retrograde tracing were carried out at the 8th week after operation to observe the regeneration of nerve fibers. The Basso, Beattie, and Bresnahan (BBB) locomotor score was used to evaluate restoration. 1) BDA and FG immunofluorescence staining: in group C, a large number of regenerated axons were observed and some penetrated the injured area. In group B, only a small number of regenerated axons were observed and none penetrated the injured area. In group D, only sporadic regenerated nerve fibers were observed occasionally, while in group A, no axonal regeneration was observed. In group C, a small number of cones and axons emitted yellow fluorescence, and no FG-labeled cells were observed in the other groups. 2) The BBB scores for group C were higher than those for the other groups, and the differences were statistically significance (P < 0.05). NSC transplantation combined with EPO intraperitoneal injection may benefit axon regeneration in rats with transected spinal cord injury, and accelerate the functional recovery of the hindlimb locomotor.

  7. Effects of Unpredictable Variable Prenatal Stress (UVPS) on Bdnf DNA Methylation and Telomere Length in the Adult Rat Brain

    NASA Technical Reports Server (NTRS)

    Blaze, Jennifer; Asok, A.; Moyer, E. L.; Roth, T. L.; Ronca, A. E.

    2015-01-01

    In utero exposure to stress can shape neurobiological and behavioral outcomes in offspring, producing vulnerability to psychopathology later in life. Animal models of prenatal stress likewise have demonstrated long-­-term alterations in brain function and behavioral deficits in offspring. For example, using a rodent model of unpredictable variable prenatal stress (UVPS), in which dams are exposed to unpredictable, variable stress across pregnancy, we have found increased body weight and anxiety-­-like behavior in adult male, but not female, offspring. DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could be responsible for the long-­-term effects of UVPS. Here, we measured methylation of brain-­-derived neurotrophic factor (bdnf), a gene important in development and plasticity, and telomere length in the brains of adult offspring from the UVPS model. Results indicate that prenatally stressed adult males have greater methylation in the medial prefrontal cortex (mPFC) compared to non-­-stressed controls, while females have greater methylation in the ventral hippocampus compared to controls. Further, prenatally stressed males had shorter telomeres than controls in the mPFC. These findings demonstrate the ability of UVPS to produce epigenetic alterations and changes in telomere length across behaviorally-­-relevant brain regions, which may have linkages to the phenotypic outcomes.

  8. The effect of high-energy extracorporeal shock waves on hyaline cartilage of adult rats in vivo.

    PubMed

    Mayer-Wagner, Susanne; Ernst, Judith; Maier, Markus; Chiquet, Matthias; Joos, Helga; Müller, Peter E; Jansson, Volkmar; Sievers, Birte; Hausdorf, Jörg

    2010-08-01

    The aim of this study was to determine if extracorporeal shock wave therapy (ESWT) in vivo affects the structural integrity of articular cartilage. A single bout of ESWT (1500 shock waves of 0.5 mJ/mm(2)) was applied to femoral heads of 18 adult Sprague-Dawley rats. Two sham-treated animals served as controls. Cartilage of each femoral head was harvested at 1, 4, or 10 weeks after ESWT (n = 6 per treatment group) and scored on safranin-O-stained sections. Expression of tenascin-C and chitinase 3-like protein 1 (Chi3L1) was analyzed by immunohistochemistry. Quantitative real-time polymerase chain reaction (PCR) was used to examine collagen (II)alpha(1) (COL2A1) expression and chondrocyte morphology was investigated by transmission electron microscopy no changes in Mankin scores were observed after ESWT. Positive immunostaining for tenascin-C and Chi3L1 was found up to 10 weeks after ESWT in experimental but not in control cartilage. COL2A1 mRNA was increased in samples 1 and 4 weeks after ESWT. Alterations found on the ultrastructural level showed expansion of the rough-surfaced endoplasmatic reticulum, detachment of the cell membrane and necrotic chondrocytes. Extracorporeal shock waves caused alterations of hyaline cartilage on a molecular and ultrastructural level that were distinctly different from control. Similar changes were described before in the very early phase of osteoarthritis (OA). High-energy ESWT might therefore cause degenerative changes in hyaline cartilage as they are found in initial OA. Copyright 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  9. Repeated forced swim stress has additive effects in anxiety behavior and in cathecolamine levels of adult rats exposed to deltamethrin.

    PubMed

    Habr, Soraya F; Macrini, Daclé J; Florio, Jorge C; Bernardi, Maria M

    2014-01-01

    Deltamethrin (DTM) is a type II pyrethroid insecticide that elicits autonomic and neuroendocrine responses that indicate high levels of stress, presumably caused by the neurotoxic effect of the insecticide. This study investigated the effect of DTM exposure (10 mg/kg, p.o.) and an additional stress induced in the forced swim test (FST) in behavioral tasks related to anxiety, serum corticosterone levels, and striatal neurotransmitter levels. Open field behavior and social interaction were evaluated after DTM administration (10 mg kg(-1), p.o). DTM per se reduced rearing frequency in the open field, but no alterations in locomotion frequency or immobility duration were detected. Stress increased immobility duration compared with non-stressed animals. DTM reduced social interaction and increased corticosterone levels, and these effects were enhanced in stressed animals. Mainly stress affected dopaminergic and serotoninergic activity. In anxiety behavior and in both neurotransmitters and metabolites levels it was observed an additive effect of stress in DTM treated rat data. These results indicate that DTM enhanced the anxiogenic responses and stress had an additive effect over the DTM stress. The neurochemical data did not indicate an interaction between stress and DTM exposure. The present results maybe important for implementing pyrethroid insecticide safety standards.

  10. Long-term effects of neonatal alcohol exposure on photic reentrainment and phase-shifting responses of the activity rhythm in adult rats.

    PubMed

    Allen, Gregg C; Farnell, Yuhua Z; Maeng, Ji-ung; West, James R; Chen, Wei-Jung A; Earnest, David J

    2005-10-01

    In rats, neonatal alcohol (EtOH) exposure coinciding with the period of rapid brain growth produces structural damage in some brain regions that often persists into adulthood and thus may have long-term consequences in the neural regulation of behavior. Because recent findings indicate that the circadian clock located in the rat suprachiasmatic nucleus is vulnerable to alcohol-induced insults during development, the present study examined the long-term effects of neonatal alcohol exposure on the photic regulation of circadian behavior in adult rats. Rat pups were exposed to alcohol (3.0, 4.5, or 6.0 g x kg(-1) x day(-1)) or isocaloric milk formula on postnatal days 4-9 using artificial-rearing methods. At 2 months of age, animals were housed individually and circadian wheel-running behavior was continuously analyzed to determine the effects of neonatal alcohol treatment on the rate of reentrainment to a 6-h advance in the 12-h light:12-h dark photoperiod and the phase-shifting properties of free-running rhythms in response to discrete light pulses on a background of constant darkness. For all doses, neonatal alcohol exposure had a significant effect in reducing the time for reentrainment such that EtOH-treated rats required four to five fewer days than control animals for stable realignment of the activity rhythm to the shifted light-dark cycle. Coupled with the accelerated rate of reentrainment, the amplitude of light-evoked phase delays at circadian time 14 and advances at circadian time 22 in the 4.5 and 6.0 g x kg(-1) x day(-1) EtOH groups was almost twofold greater than that observed in control animals. The present observations indicate that the mechanisms by which photic signals regulate circadian behavior are permanently altered following alcohol exposure during the period of rapid brain development. These long-term alterations in the photic regulation of circadian rhythms may account, at least partially, for some neurobehavioral consequences of prenatal

  11. Effect of prenatal protein malnutrition on numbers of neurons in the principal cell layers of the adult rat hippocampal formation.

    PubMed

    Lister, James P; Blatt, Gene J; DeBassio, William A; Kemper, Thomas L; Tonkiss, John; Galler, Janina R; Rosene, Douglas L

    2005-01-01

    Malnutrition has been associated with a variety of functional and anatomical impairments of the hippocampal formation. One of the more striking of these is widespread loss of hippocampal neurons in postnatally malnourished rats. In the present study we have investigated the effect of prenatal malnutrition on these same neuronal populations, neurons that are all generated during the period of the dietary restriction. In prenatally protein deprived rats, using design-based stereology, we have measured the regional volume and number of neurons in the hilus of the dentate gyrus and the pyramidal cell layers of CA3, CA2, CA1, and the subiculum of 90-day-old animals. These results demonstrated a statistically significant reduction of 20% in neuron numbers in the CA1 subfield, while numbers in the other subfields were unchanged. There was a corresponding significant reduction of 22% in the volume of the CA1 subfield and a significant 14% decrease in the volume of the pyramidal layer of the subiculum. The change in volume of the pyramidal layer of the subiculum without neuron loss may reflect loss of CA1 afferent input to the pyramidal layer. Although the effect of nutritional deprivation on the neuronal population appears to be different in pre- and postnatal malnutrition, both dietary paradigms highlight the vulnerability of key components of the hippocampal trisynaptic circuit (consisting of the dentate granule cell mossy fibers projection to CA3 pyramids and the CA3 projection to the CA1 pyramids), which is an essential circuit for memory and learning. Copyright (c) 2005 Wiley-Liss, Inc.

  12. The long-term effects of FSH and triiodothyronine administration during the pubertal period on Connexin 43 expression and spermatogenesis efficiency in adult rats.

    PubMed

    Marchlewska, Katarzyna; Slowikowska-Hilczer, Jolanta; Walczak-Jedrzejowska, Renata; Oszukowska, Elzbieta; Filipiak, Eliza; Kula, Krzysztof

    2015-04-01

    Follicle-stimulating hormone (FSH) and triiodothyronine (T3) are known regulatory factors of spermatogenesis initiation. Hyperstimulation of both hormones evokes regressional changes in connexin 43 expression and the seminiferous epithelium in young rats during testicular maturation. However, separate treatments with T3 reduce Sertoli cell number, which seems to be closely connected with the maturation of connexin 43 gap junctions. FSH elevates Sertoli cell number and function, but this effect may take place regardless of the presence of connexin 43-dependent intercellular communication. The aim of the study was to evaluate the later effects of such treatments. Newborn, male Wistar rats were divided randomly into experimental groups receiving daily subcutaneous injections of either 7.5 IU/animal FSH, or 100 mg/kg b.w. T3, or both substances or the same volume of vehicle (control group) until day 15 of life. The animals were sacrificed on day 50. Morphometric analysis and immunohistochemical reactions were performed using antibodies against Vimentin, Proliferating Cell Nuclear Antigen and Connexin 43 in the testis. Sertoli cell count, efficiency of spermatogenesis, and hormonal pattern were examined. Disturbances in the connexin 43 expression reduced the number of Sertoli cells, the efficiency of spermatogenesis and impaired endocrine function of testes in adult rats treated with FSH and T3 during puberty. Stimulation with FSH alone increased Sertoli cell number, but was associated with a negative effect on cell-to-cell connexin 43-dependent communication, with a consequential reduction of spermatogenesis efficiency. J. Exp. Zool. 323A: 256-265, 2015. © 2015 Wiley Periodicals, Inc.

  13. Cellular engineering of ventricular adult rat cardiomyocytes.

    PubMed

    Weikert, Christian; Eppenberger-Eberhardt, Monika; Eppenberger, Hans M

    2003-10-01

    Preparation of viable cultured adult cardiomyocytes (vARCs) is a prerequisite for cell-based transplantation and tissue engineering. Ectopic gene expression is important in this context. Here, we present an in vitro cell replating strategy using Accutase for cultured vARCs, allowing ectopic gene expression. Cultured vARCs from 6- to 8-week-old rats were used. Transfections with EGFP (enhanced green fluorescent protein) constructs, Mlc-3f-EGFP or alpha-actinin-EGFP were performed using adenovirus-enhanced transferrin-mediated infection (AVET). Accutase (PAA Laboratories, Linz, Austria) was used for the detachment of cultured cells. Immunohistochemical analysis, together with confocal laser microscopy was used for structural analysis of the cells. Cultured vARCs could be detached with a high yield (40 to 60%) from primary cultures using Accutase. The cultivation period plays an important role in the yield of viable cells. Resultant replated vARCs (rep-vARCs) rapidly (1-2 h) acquired a rounded up shape without degradation of their contractile apparatus, which is in contrast to the rod-shaped freshly isolated vARCs (fi-vARCs). The detached cells survived passage through a narrow syringe needle. After seeding, detached cells rapidly attached to various substrates, increased their content of the contractile apparatus, and formed cell-cell contacts within 3 days after reseeding. The detached cells survived passage through a narrow syringe needle. The high recovery of cells after replating enabled the use of the AVET system for gene delivery. AVET is free of infectious particles and does not lead to expression of viral proteins. Transfection of vARCs prior to detachment had a small effect on cell recovery and ectopically synthesized proteins were properly localized after replating. Detachment of cultured vARCs using Accutase is well compatible with ectopic gene expression and yields a viable transgenic population of vARCs that eventually may be suitable as transgenic

  14. Endotoxemia in newborn rats attenuates acute pancreatitis at adult age.

    PubMed

    Jaworek, J; Konturek, S J; Macko, M; Kot, M; Szklarczyk, J; Leja-Szpak, A; Nawrot-Porabka, K; Stachura, J; Tomaszewska, R; Siwicki, A; Pawlik, W W

    2007-03-01

    Bacterial endotoxin (lipopolysaccharide, LPS), at high concentration is responsible for sepsis, and neonatal mortality, however low concentration of LPS protected the pancreas against acute damage. The aim of this study was to investigate the effect of exposition of suckling rats to LPS on the course of acute pancreatitis at adult age. Suckling rat (30-40g) received intraperitoneal (i.p.) injection of saline (control) or LPS from Escherichia coli or Salmonella typhi (5, 10 or 15 mg/kg-day) during 5 consecutive days. Two months later these rats have been subjected to i.p. cearulein infusion (25 microg/kg) to produce caerulein-induced pancreatitis (CIP). The following parameters were tested: pancreatic weight and morphology, plasma amylase and lipase activities, interleukin 1beta (IL-1 beta), interleukin 6 (IL-6), and interleukin 10 (IL-10) plasma concentrations. Pancreatic concentration of superoxide dismutase (SOD) and lipid peroxidation products; malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) have been also measured. Caerulein infusion produced CIP in all animals tested, that was confirmed by histological examination. In the rats, which have been subjected in the neonatal period of life to LPS at doses 10 or 15 mg/kg-day x 5 days, all manifestations of CIP have been reduced. In these animals acute inflammatory infiltration of pancreatic tissue and pancreatic cell vacuolization have been significantly diminished. Also pancreatic weight, plasma lipase and alpha-amylase activities, as well as plasma concentrations of IL-1beta and IL-6 have been markedly decreased, whereas plasma anti-inflammatory IL-10 concentration was significantly increased in these animals as compared to the control rats, subjected in the infancy to saline injection instead of LPS. Caerulein-induced fall in pancreatic SOD concentration was reversed and accompanied by significant reduction of MDA + 4 HNE in the pancreatic tissue. The effects of LPS derived from E. coli or S. typhi were similar

  15. Effects of ethanol, Δ(9)-tetrahydrocannabinol, or their combination on object recognition memory and object preference in adolescent and adult male rats.

    PubMed

    Swartzwelder, Nicholas A; Risher, M Louise; Abdelwahab, Sabri H; D'Abo, Anouska; Rezvani, Amir H; Levin, Edward D; Wilson, Wilkie A; Swartzwelder, H Scott; Acheson, Shawn K

    2012-10-03

    Recent advances have been made in our understanding of the deleterious effects of both ethanol and THC on adolescent behavior and brain development. However, very little is known about the combined effects of EtOH+THC during adolescence, a time in which these drugs are often used together. The purpose of this experiment was to: (1) determine whether EtOH and/or THC induced greater working memory impairment in adolescent than adult male rats using the novel object recognition (NOR) task and (2) determine whether the EtOH+THC combination would produce a more potent additive effect in adolescents than adults when compared to these drugs alone. NOR was performed with a 24h delay under each of the four drug conditions: vehicle; 1.5g/kg ethanol; 1.0mg/kg THC; and 1.5g/kg EtOH+1.0mg/kg THC, at 72h intervals. The results show that there was an age effect on working memory in NOR after the EtOH+THC challenge. Specifically, adolescent animals showed a preference for the familiar object whereas adults showed no preference for the novel or familiar object, the latter being characteristic of a classic working memory deficit. These effects were not dependent on changes in exploration across session, global activity across drug condition, or total object exploration. These novel findings clearly indicate that further understanding of this age-drug interaction is crucial to elucidating the influence that adolescent EtOH+THC use may have on repeated drug use and abuse later in life. Published by Elsevier Ireland Ltd.

  16. Anxiolytic-like effect of hydroalcoholic extract of ripe pistachio hulls in adult female Wistar rats and its possible mechanisms.

    PubMed

    Rostampour, Mohammad; Hadipour, Elham; Oryan, Shahrbano; Soltani, Bahram; Saadat, Farshid

    2016-12-01

    The present study was designed to study the preventive effect of hydroalcoholic extract of ripe pistachio hulls (RPH) in the elevated plus maze model of anxiety. One hundred twenty female wistar rats in their estrous cycle were divided into 15 groups of 8 each and received various concentrations of hydroalcoholic extract of RPH except the control groups. Elevated plus maze was used to measure the level of anxiety. Percentage of time spent in the open arms (%OAT), percentage of the number of entries into the open arms (%OAE), locomotor activity, and time spent in the closed arms (CAT), and the number of entries in to the closed arms (CAE) were measured and compared. Dose-response experiments showed that only 10 mg/kg dose of RPH extract significantly increased %OAT (P < 0.001) and %OAE (P < 0.05) compared to the control group, indicating anti-anxiety effects of the extract. Also, pentylenetetrazol and an estrogen receptor antagonist (ERA) tamoxifen could block anti-anxiety effects of the extract (P < 0.001). It was also noticed that tamoxifen was able to significantly reduce locomotor activity. As the RPH extract showed a preventive effect in experimental model of anxiety, it might be concomitantly administered with other anxiolytic medications.

  17. Anxiolytic-like effect of hydroalcoholic extract of ripe pistachio hulls in adult female Wistar rats and its possible mechanisms

    PubMed Central

    Rostampour, Mohammad; Hadipour, Elham; Oryan, Shahrbano; Soltani, Bahram; Saadat, Farshid

    2016-01-01

    The present study was designed to study the preventive effect of hydroalcoholic extract of ripe pistachio hulls (RPH) in the elevated plus maze model of anxiety. One hundred twenty female wistar rats in their estrous cycle were divided into 15 groups of 8 each and received various concentrations of hydroalcoholic extract of RPH except the control groups. Elevated plus maze was used to measure the level of anxiety. Percentage of time spent in the open arms (%OAT), percentage of the number of entries into the open arms (%OAE), locomotor activity, and time spent in the closed arms (CAT), and the number of entries in to the closed arms (CAE) were measured and compared. Dose-response experiments showed that only 10 mg/kg dose of RPH extract significantly increased %OAT (P < 0.001) and %OAE (P < 0.05) compared to the control group, indicating anti-anxiety effects of the extract. Also, pentylenetetrazol and an estrogen receptor antagonist (ERA) tamoxifen could block anti-anxiety effects of the extract (P < 0.001). It was also noticed that tamoxifen was able to significantly reduce locomotor activity. As the RPH extract showed a preventive effect in experimental model of anxiety, it might be concomitantly administered with other anxiolytic medications. PMID:28003838

  18. Effects of Traumatic Stress Induced in the Juvenile Period on the Expression of Gamma-Aminobutyric Acid Receptor Type A Subunits in Adult Rat Brain

    PubMed Central

    Lu, Cui Yan; Liu, De Xiang; Jiang, Hong; Ho, Cyrus S. H.; Ho, Roger C. M.

    2017-01-01

    Studies have found that early traumatic experience significantly increases the risk of posttraumatic stress disorder (PTSD). Gamma-aminobutyric acid (GABA) deficits were proposed to be implicated in development of PTSD, but the alterations of GABA receptor A (GABAAR) subunits induced by early traumatic stress have not been fully elucidated. Furthermore, previous studies suggested that exercise could be more effective than medications in reducing severity of anxiety and depression but the mechanism is unclear. This study used inescapable foot-shock to induce PTSD in juvenile rats and examined their emotional changes using open-field test and elevated plus maze, memory changes using Morris water maze, and the expression of GABAAR subunits (γ2, α2, and α5) in subregions of the brain in the adulthood using western blotting and immunohistochemistry. We aimed to observe the role of GABAAR subunits changes induced by juvenile trauma in the pathogenesis of subsequent PTSD in adulthood. In addition, we investigated the protective effects of exercise for 6 weeks and benzodiazepine (clonazepam) for 2 weeks. This study found that juvenile traumatic stress induced chronic anxiety and spatial memory loss and reduced expression of GABAAR subunits in the adult rat brains. Furthermore, exercise led to significant improvement as compared to short-term BZ treatment. PMID:28352479

  19. Contextual fear conditioning differs for infant, adolescent, and adult rats

    PubMed Central

    Esmorís-Arranz, Francisco J.; Méndez, Cástor; Spear, Norman E.

    2009-01-01

    Contextual fear conditioning was tested in infant, adolescent, and adult rats in terms of Pavlovian conditioned suppression. When a discrete auditory conditioned stimulus (CS) was paired with footshock (unconditioned stimulus, US) within the largely olfactory context, infants and adolescents conditioned to the context with substantial effectiveness but adult rats did not. When unpaired presentations of the CS and US occurred within the context, contextual fear conditioning was strong for adults, weak for infants, but about as strong for adolescents as when pairings of CS and US occurred in the context. Nonreinforced presentations of either the CS or context markedly reduced contextual fear conditioning in infants, but, in adolescents, CS extinction had no effect on contextual fear conditioning, although context extinction significantly reduced it. Neither CS extinction nor context extinction affected responding to the CS-context compound in infants, suggesting striking discrimination between the compound and its components. Female adolescents showed the same lack of effect of component extinction on response to the compound as infants, but CS extinction reduced responding to the compound in adolescent males, a sex difference seen also in adults. Theoretical implications are discussed for the development of perceptual-cognitive processing and hippocampus role. PMID:18343048

  20. Immediate and prolonged effects of alcohol exposure on the activity of the hypothalamic-pituitary-adrenal axis in adult and adolescent rats

    PubMed Central

    ALLEN, Camryn D.; LEE, Soon; KOOB, George F.; RIVIER, Catherine

    2011-01-01

    Alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) axis. Part of this influence is likely exerted directly at the level of the corticotropin-releasing factor (CRF) gene, but intermediates may also play a role. Here we review the effect of alcohol on this axis, provide new data on the effects of binge drinking during adolescence, and argue for a role of catecholaminergic circuits. Indeed, acute injection of this drug activates brain stem adrenergic and noradrenergic circuits, and their lesion, or blockade of α1 adrenergic receptors significantly blunts alcohol-induced ACTH release. As alcohol can influence the HPA axis even once discontinued, and alcohol consumption in young people is associated with increased adult drug abuse (a phenomenon possibly mediated by the HPA axis), we determined whether alcohol consumption during adolescence modified this axis. The number of CRF-immunoreactive (ir) cells/section was significantly decreased in the central nucleus of the amygdala of adolescent self-administering binge-drinking animals, compared to controls. When another group of adolescent binge-drinking rats was administered alcohol in adulthood, the number of colocalized c-fos-ir and PNMT-ir cells/brain stem section in the C3 area was significantly decreased, compared to controls. As the HPA axis response to alcohol is blunted in adult rats exposed to alcohol vapors during adolescence, a phenomenon which was not observed in our model of self-administration, it is possible that the blood alcohol levels achieved in various models play a role in the long-term consequences of exposure to alcohol early in life. Collectively, these results suggest an important role of brain catecholamines in modulating the short- and long-term consequences of alcohol administration. PMID:21300146

  1. Immediate and prolonged effects of alcohol exposure on the activity of the hypothalamic-pituitary-adrenal axis in adult and adolescent rats.

    PubMed

    Allen, Camryn D; Lee, Soon; Koob, George F; Rivier, Catherine

    2011-06-01

    Alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) axis. Part of this influence is likely exerted directly at the level of the corticotropin-releasing factor (CRF) gene, but intermediates may also play a role. Here we review the effect of alcohol on this axis, provide new data on the effects of binge drinking during adolescence, and argue for a role of catecholaminergic circuits. Indeed, acute injection of this drug activates brain stem adrenergic and noradrenergic circuits, and their lesion, or blockade of α1 adrenergic receptors significantly blunts alcohol-induced ACTH release. As alcohol can influence the HPA axis even once discontinued, and alcohol consumption in young people is associated with increased adult drug abuse (a phenomenon possibly mediated by the HPA axis), we determined whether alcohol consumption during adolescence modified this axis. The number of CRF-immunoreactive (ir) cells/section was significantly decreased in the central nucleus of the amygdala of adolescent self-administering binge-drinking animals, compared to controls. When another group of adolescent binge-drinking rats was administered alcohol in adulthood, the number of colocalized c-fos-ir and PNMT-ir cells/brain stem section in the C3 area was significantly decreased, compared to controls. As the HPA axis response to alcohol is blunted in adult rats exposed to alcohol vapors during adolescence, a phenomenon which was not observed in our model of self-administration, it is possible that the blood alcohol levels achieved in various models play a role in the long-term consequences of exposure to alcohol early in life. Collectively, these results suggest an important role of brain catecholamines in modulating the short- and long-term consequences of alcohol administration.

  2. Effects of date palm pollen (Phoenix dactylifera L.) and Astragalus ovinus on sperm parameters and sex hormones in adult male rats

    PubMed Central

    Mehraban, Fouad; Jafari, Mehrzad; Akbartabar Toori, Mehdi; Sadeghi, Hossein; Joodi, Behzad; Mostafazade, Mostafa; Sadeghi, Heibatollah

    2014-01-01

    Background: Date Palm Pollen (DPP) and Astragalus genus are used in some countries for the treatment of infertility. Objective: This study was designed to investigate effects of DPP and Astragalus ovinus (A.Ovinus) on fertility in healthy adult male rats. Materials and Methods: Thirty-six rats were divided into six groups (n=6) including control and five treatment groups. DPP (120, 240 and 360 mg/kg) and A.ovinus (100, 500 mg/ kg) were orally given to the treatment groups. After thirty-five days, blood samples were taken to determine serum levels of FSH, LH, testosterone and estradiol. Weight of testis and epididymis, sperm count, sperm motility, seminiferous tubules diameter (STD), germinal cell layer thickness (GCLT), sertoli, leydig and spermatogonia cells were also evaluated. Results: DPP at the of 120 and 240 mg/kg doses significantly raised the ratio of testis or epididymis to body weight, sperm count, sperm motility , and estradiol level compared to the control group (p<0.05). LH and testosterone levels only noticeably increased at 120 mg/kg of DPP (p<0.01 and p<0.001 respectively). STD increased in the three applied doses (p=0.001). A. ovinus extract at the indicated doses produced a significant reduction in the ratio of testis or epididymis to body weight and sperm motility (p<0.05). Sperm count, spermatogonia, leydig cells and FSH level decreased at dose of 500 mg/kg. Furthermore, GCLT, spermatogonia cells, and serum estradiol level increased at 100 mg/kg dose of A. ovinus. Conclusion: Our findings indicate that DPP could improve fertility factors, while A.ovinus can exhibit deleterious effects on gonad and sperm parameters in rats. PMID:25469129

  3. Unexpected Lack of Deleterious Effects of Uranium on Physiological Systems following a Chronic Oral Intake in Adult Rat

    PubMed Central

    Dublineau, Isabelle; Souidi, Maâmar; Gueguen, Yann; Lestaevel, Philippe; Bertho, Jean-Marc; Manens, Line; Delissen, Olivia; Grison, Stéphane; Paulard, Anaïs; Monin, Audrey; Kern, Yseult; Rouas, Caroline; Loyen, Jeanne; Gourmelon, Patrick; Aigueperse, Jocelyne

    2014-01-01

    Uranium level in drinking water is usually in the range of microgram-per-liter, but this value may be as much as 100 to 1000 times higher in some areas, which may raise question about the health consequences for human populations living in these areas. Our purpose was to improve knowledge of chemical effects of uranium following chronic ingestion. Experiments were performed on rats contaminated for 9 months via drinking water containing depleted uranium (0.2, 2, 5, 10, 20, 40, or 120 mg/L). Blood biochemical and hematological indicators were measured and several different types of investigations (molecular, functional, and structural) were conducted in organs (intestine, liver, kidneys, hematopoietic cells, and brain). The specific sensitivity of the organs to uranium was deduced from nondeleterious biological effects, with the following thresholds (in mg/L): 0.2 for brain, >2 for liver, >10 for kidneys, and >20 for intestine, indicating a NOAEL (No-Observed-Adverse-Effect Level) threshold for uranium superior to 120 m g/L. Based on the chemical uranium toxicity, the tolerable daily intake calculation yields a guideline value for humans of 1350 μg/L. This value was higher than the WHO value of 30 μg/L, indicating that this WHO guideline for uranium content in drinking water is very protective and might be reconsidered. PMID:24693537

  4. Effects of co-exposure to imidacloprid and gibberellic acid on redox status, kidney variables and histopathology in adult rats.

    PubMed

    Lafi, Bornia; Chaâbane, Mariem; Elwej, Awatef; Grati, Malek; Jamoussi, Kamel; Mnif, Hela; Boudawara, Tahia; Ketata Bouaziz, Hanen; Zeghal, Najiba

    2017-09-06

    Data on the individual nephrotoxic effects of imidacloprid (IMI) and gibberellic acid (GA3) are scarce. Moreover, there is a lack of information about their combined effects on the renal tissue. Our study investigated the effects of IMI and GA3 separately or together on rats kidney. IMI (64 mg/kg bw) was given for 3 weeks by gavage either individually or in combination with GA3 (200 mg/L) via drinking water. IMI associated or no with GA3 increased the levels of kidney malondialdehyde, advanced oxidation protein products, protein carbonyls and metallothionein, plasma creatinine, urea, blood urea nitrogen and lactate dehydrogenase activity. A decline of kidney uric acid level and antioxidant status was also observed. All these changes were supported by histopathological observations. Our results highlighted the role of IMI and/or GA3-induced nephrotoxicity. Co-exposure to IMI and GA3 exhibited synergism in biochemical kidney variables and histopathology and antagonism in physical and morphological parameters.

  5. Interactions between respiratory oscillators in adult rats

    PubMed Central

    Huckstepp, Robert TR; Henderson, Lauren E; Cardoza, Kathryn P; Feldman, Jack L

    2016-01-01

    Breathing in mammals is hypothesized to result from the interaction of two distinct oscillators: the preBötzinger Complex (preBötC) driving inspiration and the lateral parafacial region (pFL) driving active expiration. To understand the interactions between these oscillators, we independently altered their excitability in spontaneously breathing vagotomized urethane-anesthetized adult rats. Hyperpolarizing preBötC neurons decreased inspiratory activity and initiated active expiration, ultimately progressing to apnea, i.e., cessation of both inspiration and active expiration. Depolarizing pFL neurons produced active expiration at rest, but not when inspiratory activity was suppressed by hyperpolarizing preBötC neurons. We conclude that in anesthetized adult rats active expiration is driven by the pFL but requires an additional form of network excitation, i.e., ongoing rhythmic preBötC activity sufficient to drive inspiratory motor output or increased chemosensory drive. The organization of this coupled oscillator system, which is essential for life, may have implications for other neural networks that contain multiple rhythm/pattern generators. DOI: http://dx.doi.org/10.7554/eLife.14203.001 PMID:27300271

  6. Toluene effects on the motor activity of adolescent, young-adult, middle-age and senescent male Brown Norway rats.

    EPA Science Inventory

    Life stage is an important risk factor for toxicity. Children and aging adults, for example, are more susceptible to certain chemicals than are young adults. In comparison to children, relatively little is known about susceptibility in older adults. Additionally, few studies have...

  7. Toluene effects on the motor activity of adolescent, young-adult, middle-age and senescent male Brown Norway rats.

    EPA Science Inventory

    Life stage is an important risk factor for toxicity. Children and aging adults, for example, are more susceptible to certain chemicals than are young adults. In comparison to children, relatively little is known about susceptibility in older adults. Additionally, few studies have...

  8. Combine effect of Chondroitinase ABC and low level laser (660nm) on spinal cord injury model in adult male rats.

    PubMed

    Janzadeh, Atousa; Sarveazad, Arash; Yousefifard, Mahmoud; Dameni, Sima; Samani, Fazel Sahraneshin; Mokhtarian, Kobra; Nasirinezhad, Farinaz

    2017-07-14

    After spinal cord injury (SCI) there are many recoveries inhibiting factors such as chondroitin sulfate proteoglycan (CSPG) and inflammation. The present study investigated the combinational effect of low level laser therapy (LLLT) as anti-inflammatory agent and Chondroitinase ABC (ChABC) enzyme as CSPG digesting factor on spinal cord after injury. This study performed on 44 male Wistar rats, spinal cord injury induced by a clip compression injury. Animals received two-weeks treatment of 660nm low level laser (LLL) and intraspinal injection of 1μg ChABC. Functional recovery, cavity size, myelination, axonal projections around the cavity, fibroblast invasion and expression of glycogen synthase kinase-3β (GSk 3β), CSPG and aquaporin 4 (AQP4) expression were evaluated. In statistical evaluation p<0.05 considered significant. Result showed the combination of LLLT and ChABC have more effect on reduction of cavity size, improvement of myelination and number of axons around the cavity and decreasing the expression of GSK3β, CSPG and AQP4 expression compared to LLLT and ChABC alone. In the laser and laser+enzyme groups AQP4 expression decreased significantly after SCI. Functional recovery, improved in LLLT and ChABC treated animals, but higher recovery belonged to the combination therapy group. The current study showed combination therapy by LLLT and ChABC is more efficient than a single therapy with each of them. Copyright © 2017. Published by Elsevier Ltd.

  9. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain.

    PubMed

    Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.

  10. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

    PubMed Central

    Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J.; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence. PMID:26483633

  11. Effects of depressant amino acids and antagonists on an in vitro spinal cord preparation from the adult rat.

    PubMed

    Long, S K; Evans, R H; Krijzer, F

    1989-07-01

    A mature sacrococcygeal in vitro spinal preparation from the rat has been used to demonstrate effects of neutral amino acids and their antagonists. gamma-Aminobutanoate (GABA), glycine and taurine (0.5-5 mM) produced dose-dependent depression of spontaneous paroxysmal activity generated in Mg2+ -free medium. The depressant effect of GABA was antagonised selectively by picrotoxin (25-50 microM) and the depressant effects of glycine and taurine were antagonised selectively by strychnine (0.2 microM). Glycine (0.5-5 mM) had a dose-dependent depolarizing action which was present at the central ends of isolated ventral roots. gamma-Aminobutanoate and taurine, had only weak depolarizing actions on ventral root fibres. Depolarizing responses to glycine showed a marked fading. Reduction in the fading appeared to be responsible for a paradoxical potentiation of glycine-induced depolarizations, which occurred in the presence of strychnine (0.2-2 microM). Strychnine (2-10 microM), picrotoxin (10-50 microM) or bicuculline (10 microM) had little or no effect on the amplitude, duration or latency of the monosynaptic component of ventral root reflexes evoked by supramaximal stimulation of dorsal roots (DR-VRP). However all three antagonists introduced slow, NMDA receptor mediated, components to these ventral root potentials. Picrotoxin and bicuculline, but not strychnine, reversibly depressed the dorsal root potential evoked from an adjacent dorsal root (DR-DRP). The depressant actions of 2-amino-5-phosphonopentanoate (AP5), kynurenate and 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) revealed both NMDA and non-NMDA receptor mediated components in the dorsal root potential.

  12. Short-term effect of a high-protein/low-carbohydrate diet on aminopeptidase in adult rat jejunoileum. Site of aminopeptidase response.

    PubMed

    Raul, F; Goda, T; Gossé, F; Koldovský, O

    1987-10-15

    The short-term effects of high-protein/low-carbohydrate diet on aminopeptidase N activity were studied in the brush-border membranes of proximal jejunum and proximal ileum of adult rats. The animals were starved overnight and re-fed for 15 h either with a standard diet (20% protein, 55% carbohydrate, in terms of energy content) or with a high-protein/low-carbohydrate diet of equal energy content (70% protein, 5% carbohydrate). All rats consumed similar amounts of diet, and measurements were made 15 h after initiation of re-feeding. In the proximal jejunum a slight increase in aminopeptidase activity was observed after the high-protein intake. In contrast, considerable stimulation (52%) of the enzyme specific activity was obtained in the proximal ileum. This increase in ileal aminopeptidase activity was more prominent in the mature cells of the upper villus. To determine if the increase of aminopeptidase activity was due to an increased amount of enzyme protein, rocket immunoelectrophoresis was performed with detergent-solubilized brush-border protein from ileum on agarose gels containing anti-(rat brush-border) antiserum. When the same amount of enzyme activity was loaded on the gels, the peaks of immunoprecipitate for aminopeptidase were similar for animals fed on a standard or a high-protein diet. When the same amount of protein was loaded, the peak of immunoprecipitate for aminopeptidase was higher (81%) after a high-protein diet. These results showed that the high protein intake evoked an increase in aminopeptidase activity, with a concomitant increase in the amount of immunoreactive protein.

  13. The Association Between Effective Dose of Magnesium and Mild Compulsive Exercise on Spatial Learning, Memory, and Motor Activity of Adult Male Rats.

    PubMed

    Hajizade Ghonsulakandi, Shahnaz; Sheikh, Mahmuod; Dehghan Shasaltaneh, Marzieh; Chopani, Samira; Naghdi, Nasser

    2017-01-25

    One of the most important survival mechanisms is learning and memory processes. To emphasize the role of physical exercises and magnesium (Mg) in improvement of cognitive performance, we planned to investigate the effect of Mg and mild compulsive exercise on spatial learning and memory of adult male rats. Accordingly, we divided male Wistar rats into four groups: (I) control, (II) Mg treatment, (III) exercise, and (IV) Mg-exercise in the different dosages of Mg (0.5, 1, 1.5, and 2 mmol/kbw) were injected in the form of gavage during 1 week. Also, 1-week mild running on treadmill was used for exercise treatment. The Morris water maze (MWM) test and open field tool were used to evaluate spatial learning, memory, and motor activity, respectively. Our results clearly showed that 1 mmol/kbw Mg was applied as an effective dosage. Strikingly, 1-week mild exercise on treadmill had no significant effect on spatial motor activity, learning, and memory. Feeding 1 mmol/kbw Mg for a week showed a significant difference in learning and exploration stages. Compared to control animals, these results reveal exercise and Mg simultaneously had effect on learning and reminding. As a consequence, although mild exercise had no effect on motor activity and memory, Mg intake improved spatial learning, memory, and locomotor activity. The Mg feeding could be a promising supplemental treatment in the neurodegenerative disease. It is worthwhile to mention consumption of Mg leads to enhancement of memory, so animals find the hidden platform with the highest velocity.

  14. Ro 04-6790-induced cognitive enhancement: no effect in trace conditioning and novel object recognition procedures in adult male Wistar rats.

    PubMed

    Thur, K E; Nelson, A J D; Cassaday, H J

    2014-12-01

    The evidence for cognitively enhancing effects of 5-hydroxytryptamine6 (5-HT6) receptor antagonists such as Ro 04-6790 is inconsistent and seems to depend on the behavioral test variant in use. Trace conditioning holds promise as a behavioral assay for hippocampus-dependent working memory function. Accordingly, Experiment 1 assessed the effect of Ro 04-6790 (5 and 10mg/kg i.p.) on associating a noise conditioned stimulus paired with foot shock (unconditioned stimulus) at a 3 or 30s trace interval in adult male Wistar rats. Contextual conditioning was measured as suppression to the contextual cues provided by the experimental chambers and as suppression to a temporally extended light background stimulus which provided an experimental context. Experiment 2 assessed the effect of Ro 04-6790 (5 and 10mg/kg i.p.) on recognition memory as tested by the exploration of novel relative to familiar objects in an open arena. In Experiment 1, Ro 04-6790 (5 and 10mg/kg) was without effect on trace and contextual conditioning. In Experiment 2, there was no indication of the expected improvement under Ro 04-6790 at the same doses previously found to enhance recognition memory as measured in tests of novel object exploration. Thus, there was no evidence that treatment with the 5-HT6 receptor antagonist Ro 04-6790 acted as a cognitive enhancer in either trace conditioning or object recognition procedures. We cannot exclude the possibility that the experimental procedures used in the present study would have been sensitive to the cognitive enhancing effects of Ro 04-6790 in a different dose range, behavioral test variant, or in a different strain of rat. Nonetheless the drug treatment was not ineffective in that object exploration was reduced under 10mg/kg Ro 04-6790.

  15. Ro 04-6790-induced cognitive enhancement: No effect in trace conditioning and novel object recognition procedures in adult male Wistar rats

    PubMed Central

    Thur, K.E.; Nelson, A.J.D.; Cassaday, H.J.

    2014-01-01

    The evidence for cognitively enhancing effects of 5-hydroxytryptamine6 (5-HT6) receptor antagonists such as Ro 04-6790 is inconsistent and seems to depend on the behavioral test variant in use. Trace conditioning holds promise as a behavioral assay for hippocampus-dependent working memory function. Accordingly, Experiment 1 assessed the effect of Ro 04-6790 (5 and 10 mg/kg i.p.) on associating a noise conditioned stimulus paired with foot shock (unconditioned stimulus) at a 3 or 30 s trace interval in adult male Wistar rats. Contextual conditioning was measured as suppression to the contextual cues provided by the experimental chambers and as suppression to a temporally extended light background stimulus which provided an experimental context. Experiment 2 assessed the effect of Ro 04-6790 (5 and 10 mg/kg i.p.) on recognition memory as tested by the exploration of novel relative to familiar objects in an open arena. In Experiment 1, Ro 04-6790 (5 and 10 mg/kg) was without effect on trace and contextual conditioning. In Experiment 2, there was no indication of the expected improvement under Ro 04-6790 at the same doses previously found to enhance recognition memory as measured in tests of novel object exploration. Thus, there was no evidence that treatment with the 5-HT6 receptor antagonist Ro 04-6790 acted as a cognitive enhancer in either trace conditioning or object recognition procedures. We cannot exclude the possibility that the experimental procedures used in the present study would have been sensitive to the cognitive enhancing effects of Ro 04-6790 in a different dose range, behavioral test variant, or in a different strain of rat. Nonetheless the drug treatment was not ineffective in that object exploration was reduced under 10 mg/kg Ro 04-6790. PMID:25450117

  16. Effects of MAO inhibition and a combination of minor alkaloids, β-carbolines, and acetaldehyde on nicotine self-administration in adult male rats*

    PubMed Central

    Smith, Tracy T.; Schaff, Matthew B.; Rupprecht, Laura E.; Schassburger, Rachel L.; Buffalari, Deanne M.; Murphy, Sharon E.; Sved, Alan F.; Donny, Eric C.

    2015-01-01

    Introduction Although nicotine is the primary reinforcing constituent in cigarettes, there is evidence that other constituents in cigarette smoke may interact with nicotine to reinforce smoking behavior. Methods The present experiments investigated whether a novel combination of these cigarette smoke constituents would increase nicotine self-administration in adult male rats. The constituents included five minor alkaloids (anabasine, nornicotine, cotinine, myosmine, and anatabine), two β-carbolines (harman and norharman), and acetaldehyde. All doses were indexed to be proportional to concentrations in cigarette smoke given a standard dose of nicotine used in rodent self-administration, or ten times higher than this standard. To model MAO inhibition seen in chronic smokers, some groups received separate injections of tranylcypromine prior to each self-administration session. Results Tranylcypromine increased low-dose nicotine self-administration independent of other smoke constituents, which had no effect on self-administration behavior. The effect of tranylcypromine was confirmed across a large range of reinforcement schedules. The effect of tranylcypromine on low-dose nicotine self-administration was observed regardless of whether the injection was delivered 1-hr or 23-hrs prior to the self-administration session, consistent with the interpretation that MAO inhibition was responsible for the increase in self-administration, instead of acute off-target effects. Conclusions These data suggest that this cocktail of constituents does not significantly alter the primary reinforcing effects of nicotine, but constituents that inhibit MAO may increase the primary reinforcing effects of nicotine, especially at low doses. PMID:26257022

  17. Differential effects of chronic overload-induced muscle hypertrophy on mTOR and MAPK signaling pathways in adult and aged rats

    USDA-ARS?s Scientific Manuscript database

    We examined activation of the mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) signaling pathways in adult (Y; 6 mo old; n = 16) and aged (O; 30 mo old; n = 16) male rats (Fischer 344 x Brown Norway) subjected to chronic overload-induced muscle hypertrophy of the plan...

  18. LACK OF ANTIANDROGENIC EFFECTS IN ADULT MALE RATS FOLLOWING ACUTE EXPOSURE TO 2, 2-BIS (4-CHLOROPHENYL)-1,1-DICHLOROETHYLENE (P,P'DDE)

    EPA Science Inventory

    Although the insecticide dichlorodiphenyltrichloroethane (DDT) was banned in the US in 1972, DDT and its major metabolite 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (DDE) are still persistent in the environment. DDE at high doses is antiandrogenic in fetal and adult rats and, t...

  19. LACK OF ANTIANDROGENIC EFFECTS IN ADULT MALE RATS FOLLOWING ACUTE EXPOSURE TO 2, 2-BIS (4-CHLOROPHENYL)-1,1-DICHLOROETHYLENE (P,P'DDE)

    EPA Science Inventory

    Although the insecticide dichlorodiphenyltrichloroethane (DDT) was banned in the US in 1972, DDT and its major metabolite 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (DDE) are still persistent in the environment. DDE at high doses is antiandrogenic in fetal and adult rats and, t...

  20. Methylphenidate reduces impulsive behaviour in juvenile Wistar rats, but not in adult Wistar, SHR and WKY rats.

    PubMed

    Bizot, Jean-Charles; Chenault, Nicolas; Houzé, Bérengère; Herpin, Alexandre; David, Sabrina; Pothion, Stéphanie; Trovero, Fabrice

    2007-08-01

    Impulsivity is a core symptom of attention deficit/hyperactivity disorder (ADHD). The spontaneously hypertensive rats (SHR) is a strain commonly used as an animal model of ADHD. However, there is no clear evidence that psychostimulants, which are used for treatment of ADHD, reduce impulsivity in SHR. Because ADHD mainly affects children, it may be relevant to study psychostimulants on juvenile animals. Using tolerance to delay of reward as index of impulsivity, the effects of methylphenidate were assessed in adult SHR, Wistar Kyoto (WKY) and Wistar rats and in juvenile Wistar rats. Animals were trained in a T-maze to choose between a small-but-immediate and a large-but-delayed reward. Adult SHR, WKY and Wistar rats were compared for their ability to tolerate a 15-s delay. The effect of methylphenidate on the tolerance to a 30-s delay was studied in adult rats of the three strains and in juvenile (4.5 to 6.5-week-old) Wistar rats. In adult rats, the waiting ability was lower in SHR than in control strains. Waiting ability was improved by methylphenidate (3 and 5 mg/kg) in juveniles, but not by methylphenidate (3 mg/kg) in adults. These data support the idea that SHR are more impulsive than control strains. However, at the dose studied, methylphenidate fails to improve tolerance to delay in adult rats whatever the strain used. The reduction of impulsivity induced by methylphenidate in juvenile Wistar rats indicates that juvenile animals may be suitable for testing the therapeutic potential of drugs intended to the treatment of ADHD in children.

  1. Effect of whole-body exposure to the 848.5 MHz code division multiple access (CDMA) electromagnetic field on adult neurogenesis in the young, healthy rat brain.

    PubMed

    Kim, Hye Sun; Kim, Yeon Ju; Lee, Yu Hee; Lee, Yun-Sil; Choi, Hyung Do; Pack, Jeong-Ki; Kim, Nam; Ahn, Young Hwan

    2015-04-01

    Whether exposure to the 848.5 MHz code division multiple access (CDMA) signal affects adult neurogenesis is unclear. An animal experiment was performed with a reverberation chamber designed as a whole-body CDMA exposure system. Male Sprague-Dawley rats were assigned to three groups (n = 6 per group): Cage-control, sham-exposed, and CDMA-exposed groups. Rats in the CDMA-exposed group were exposed to the CDMA signal at a 2 W/kg whole-body specific absorption rate (SAR) for 1 or 8 h daily, 5 days per week, for 2 weeks. Rats received a single intraperitoneal injection of Bromodeoxyuridine (BrdU) to label proliferative cells daily for the last five consecutive days of CDMA signal exposure. An unbiased stereological method was used to estimate the number of BrdU(+) cells in the subventricular zone (SVZ) and dentate gyrus (DG). We found no significant changes in the number of BrdU(+) cells in the SVZ or DG in the CDMA-exposed rats, compared with rats in the cage-control and sham-exposed groups (p > 0.05). Our results suggest that exposure to the CDMA signal does not affect neurogenesis in the adult rat brain, at least under our experimental conditions.

  2. 17β-estradiol replacement in young, adult and middle-aged female ovariectomized rats promotes improvement of spatial reference memory and an antidepressant effect and alters monoamines and BDNF levels in memory- and depression-related brain areas.

    PubMed

    Kiss, Agata; Delattre, Ana Márcia; Pereira, Sofia I R; Carolino, Ruither G; Szawka, Raphael E; Anselmo-Franci, Janete A; Zanata, Sílvio M; Ferraz, Anete C

    2012-02-01

    Clinical and experimental evidence suggest that estrogens have a major impact on cognition, presenting neurotrophic and neuroprotective actions in regions involved in such function. In opposite, some studies indicate that certain hormone therapy regimens may provoke detrimental effects over female cognitive and neurological function. Therefore, we decided to investigate how estrogen treatment would influence cognition and depression in different ages. For that matter, this study assessed the effects of chronic 17β-estradiol treatment over cognition and depressive-like behaviors of young (3 months old), adult (7 months old) and middle-aged (12 months old) reproductive female Wistar rats. These functions were also correlated with alterations in the serotonergic system, as well as hippocampal BDNF.