Performance Of Female Rats Research Articles

Cognitive performance is associated with cardiovascular and renal remodeling in young female rats with chronic kidney disease

AbstractBackgroundThe prevalence of cognitive impairment (CI) and dementia in end‐stage chronic kidney disease (CKD) has been estimated at 30‐60%. Cardiovascular dysfunction accompanies CKD and contributes to CI in humans and animal models. Since CKD occurs more often in females in clinical studies, the aim of this study was to determine whether cardiovascular and renal remodeling is associated with cognitive performance in the female rats with CKD.MethodsFour‐month‐old female Sprague‐Dawley rats were fed with 0.25% adenine diet to induce CKD (n = 19) or a regular control diet (n = 16; CTRL) for 8weeks. Body weight (BW), blood pressure (BP), heart rate (HR), blood urea nitrogen (BUN), sodium, potassium, creatinine, hematocrit, estradiol, and behavioral tests were assessed at the end of the study. The level of anxiety was tested in open field test (OFT) and elevated plus maze (EPM). Spatial memory was tested by the ability to find a hidden platform in Morris water maze (MWM). The data were analyzed by two‐tailed unpaired t‐test and linear regression analysis (LRA).ResultsCKD was associated with higher creatinine and BUN, lower hematocrit, and enlarged hearts, aortae and kidneys vs. CTRL (Table 1). There was no difference in BP, estradiol, sodium and potassium, MWM, OFT and EPM performance between the groups. However, the LRA revealed the association of higher heart weights with a reduced spatial memory and higher anxiety level in both CTRL and CKD (Table 2; Figure 1A,B). The association of higher aortic weight with a reduced spatial memory, and higher kidney weight with higher anxiety levels was demonstrated in CKD only (Table 2; Figure 1C,D). Estradiol was associated with better spatial memory in CKD (LRA: R2 = 0.264; p = 0.04).ConclusionAnxiety‐like behavior and spatial memory were associated with cardiovascular remodeling in young female rats with CKD. We suggest that (1) CKD stimulates development of cardiovascular remodeling, which may affect blood supply of cortex and hippocampus, responsible for anxiety and spatial memory, and (2) estradiol may contribute to a better cognitive performance in the young CKD female rats. The future direction is to investigate whether CKD influences the trajectory of neurocognitive and cardiovascular aging.Supported by NIA/NIH/IRP

Comparable assessment of adolescent repeated physical or psychological stress effects on adult cardiac performance in female rats

Extensive evidence highlights a robust connection between various forms of chronic stress and cardiovascular disease (CVD). In today's fast-paced world, with chronic stressors abound, CVD has emerged as a leading global cause of mortality. The intricate interplay of physical and psychological stressors triggers distinct neural networks within the brain, culminating in diverse health challenges. This study aims to discern the unique impacts of chronic physical and psychological stress on the cardiovascular system, unveiling their varying potencies in precipitating CVD. Twenty-one adolescent female rats were methodically assigned to three groups: (1) control (n = 7), (2) physical stress (n = 7), and (3) psychological stress (n = 7). Employing a two-compartment enclosure, stressors were administered to the experimental rats over five consecutive days, each session lasting 10 min. After a 1.5-month recovery period post-stress exposure, a trio of complementary techniques characterized by high specificity or high sensitivity were employed to meticulously evaluate CVD. Echocardiography and single-photon emission computed tomography (SPECT) were harnessed to scrutinize left ventricular architecture and myocardial viability, respectively. Subsequently, the rats were ethically sacrificed to facilitate heart removal, followed by immunohistochemistry staining targeting glial fibrillary acidic protein (GFAP). Rats subjected to psychological stress showed a wider range of significant cardiac issues compared to control rats. This included left ventricular hypertrophy [IVSd: 0.1968 ± 0.0163 vs. 0.1520 ± 0.0076, P < 0.05; LVPWd: 0.2877 ± 0.0333 vs. 0.1689 ± 0.0057, P < 0.01; LVPWs: 0.3180 ± 0.0382 vs. 0.2226 ± 0.0121, P < 0.05; LV-mass: 1.283 ± 0.0836 vs. 1.000 ± 0.0241, P < 0.01], myocardial ischemia [21.30% vs. 32.97%, P < 0.001], and neuroinflammation. This outcome underscores the imperative of prioritizing psychological well-being during adolescence, presenting a compelling avenue to curtail the prevalence of CVD in adulthood. Furthermore, extending such considerations to individuals grappling with CVD might prospectively enhance their overall quality of life.

Multiple decrements in switch task performance in female rats exposed to space radiation

Astronauts on the Artemis missions to the Moon and Mars will be exposed to unavoidable Galactic Cosmic Radiation (GCR). Studies using male rats suggest that GCR exposure impairs several processes required for cognitive flexibility performance, including attention and task switching. Currently no comparable studies have been conducted with female rats. Given that both males and females will travel into deep space, this study determined whether simulated GCR (GCRsim) exposure impairs task switching performance in female rats. Female Wistar rats exposed to 10 cGy GCRsim (n = 12) and shams (n = 14) were trained to perform a touchscreen-based switch task that mimics a switch task used to evaluate pilots’ response times. In comparison to sham rats, three-fold more GCRsim-exposed rats failed to complete the stimulus response stage of training, a high cognitive loading task. In the switch task, 50% of the GCRsim-exposed rats failed to consistently transition between the repeated and switch blocks of stimuli, which they completed during lower cognitive loading training stages. The GCRsim-exposed rats that completed the switch task only performed at 65% of the accuracy of shams. Female rats exposed to GCRsim thus exhibit multiple decrements in the switch task under high, but not low, cognitive loading conditions. While the operational significance of this performance decrement is unknown, if GCRSim exposure was to induce similar effects in astronauts, our data suggests there may be a reduced ability to execute task switching under high cognitive loading situations.

Sex differences in the acute ethanol effects on object recognition memory: influence of estrous cycle.

Effects of acute ethanol (EtOH) on memory depend on several factors, including type of behavioral task. Sex differences in EtOH effects have been reported in humans and animals, and recognition memory can be influenced by circulating sex hormones. The aim of this study was to investigate the influence of sex and estrous cycle in the acute effects of EtOH on novel object recognition memory in rats. Male and female Wistar rats were part of one of the groups: control, 0.6-g/kg EtOH and 1.8-g/kg EtOH (administered intraperitoneally before the training session). The estrous cycle was evaluated by vaginal smear. The task was conducted in an open field arena. During training, animals were exposed to two identical objects, and test sessions were performed 1 h (short-term) and 24 h (long-term) later. One of the objects was changed in each test. Increased novel object exploration was shown by male and female controls in the short- and long-term tests, respectively. In the short-term test, females did not show preference for the novel object, and EtOH 1.8 g/kg impaired performance in males. In the long-term test, both sexes showed object discrimination, and 1.8-g/kg EtOH reduced preference for the new object in male rats. The phase of the cycle, the performance on proestrus was worse compared with other phases, and EtOH failed to impair performance mainly on estrous. In conclusion, while male rats displayed ethanol-induced recognition memory deficit, female rats were unaffected by EtOH impairing effects. In addition, the performance of female rats was influenced by the estrous cycle phases.

Juvenile stress increases cocaine-induced impulsivity in female rats

In humans, adverse childhood experiences are associated with an increased risk of developing a neuropsychiatric disorder. Changes in social behavior and cognitive function are hallmarks of numerous neuropsychiatric disorders. Here we examined the effects of exposure to variable stress during the juvenile period on social behavior, reward, and cognitive function (as measured in the 5-choice serial reaction time task (5CSRTT)) in rats. From postnatal days (PND) 25–29 male and female rats were exposed to a variable stress protocol. In adulthood, social interactions and sucrose preference were assessed prior to training on the 5CSRTT. Once successfully trained, rats were challenged with different task versions, and then the effects of cocaine (0, 10, or 20 mg/kg, IP) on performance were assessed. A follow-up experiment examined the ability of the D2 receptor antagonist eticlopride (0.0, 0.025, 0.05 mg/kg, IP) to block the effects of cocaine on 5CSRTT performance in female rats. Male rats exposed to juvenile stress tended to engage in less social behavior and had an increased correct response latency in the 5CSRTT following cocaine administration. Female rats exposed to juvenile stress exhibited a trend towards increased social behavior and demonstrated increased cocaine-induced impulsivity. The increase in impulsivity was not blocked by co-administration of eticlopride. Juvenile stress had minimal effects on adult behavior in male rats, but increased cocaine-induced impulsivity in female rats. Such an effect could contribute to the enhanced escalation of drug-use observed in females that experience juvenile stress. This possibility awaits further testing.

Sex differences in noradrenergic modulation of attention and impulsivity in rats.

Noradrenaline (NE) is closely related to attentive performance and impulsive control. However, the potential sex differences regarding attention and impulsivity under the noradrenergic modulation have been largely neglected. Therefore, our study aimed to investigate whether male and female rats exhibit differential responses to NE-related drugs during the five-choice serial reaction time task (5CSRT). Male and female rats were trained in 5CSRT and administered with different NE drugs after obtaining stable baseline performance: atipamezole, a highly selective α2 receptor antagonist; prazosin, an α1 receptor antagonist; and atomoxetine, a selective NE reuptake inhibitor. Later, prazosin was selected to co-administration with atomoxetine. Male and female rats exhibited equal learning speed, and no significant baseline differences were found as measured by the 5CSRT. Atomoxetine decreased premature responses in both sexes, but the extent of this reduction was different, with the reduction greater in males. Besides, atomoxetine (1.8 mg/kg) increased the error of omissions in females. The high dose of prazosin (0.5 mg/kg) decreased the accuracy only in male rats, but this was ameliorated by the co-administration with atomoxetine. Atomoxetine showed significant improvement in impulsivity, but atomoxetine had less beneficial effects on impulsive control in females than in males, and it even impaired attentional performance in female rats. The α1 receptors were mainly responsible for NE drug-related sex differences in attention rather than impulsivity. The results obtained in this study indicate that the sex differences exist in both attention and impulsivity by the modulation of noradrenaline and raise the concern to improve sex-specific treatments.

Impaired discriminative avoidance and increased plasma corticosterone levels induced by vaginal lavage procedure in rats

Historically, females have been neglected in behavioral neuroscience research due to the alleged increased variability caused by hormonal fluctuations. More recently, there has been a tendency to include female subjects in the studies, in a majority of those cases with the condition that the hormonal variation is controlled. In rodent studies, the vaginal lavage procedure is a common method of collecting smears and determining the estrous cycle phase. However, little is known regarding the consequences of the procedure, although stress is often mentioned as a concern. Within the neuroscience field, spatial memory has been a relevant subject in terms of sex differences. The plus-maze discriminative avoidance task (PMDAT) allows for the concomitant evaluation of spatial memory, anxiety-like behavior, and locomotion, as well as possible interactions between these behaviors. The aim of the present study was to investigate the effects of the vaginal lavage procedure (VLP) on the performance of female rats in the PMDAT. We submitted adult female Wistar rats to VLP for 14 straight days and then to training and test sessions in the PMDAT. Additionally, another set of animals was submitted to the VLP procedure for determination of plasma corticosterone levels. Rats submitted to the vaginal lavage procedure did not discriminate the enclosed arms of the PMDAT apparatus, indicating impaired performance, but no anxiety-like alterations were found. VLP also resulted in a higher corticosterone level, suggesting it is a stressful manipulation. As such, the use of this method to control for hormonal variation should be restricted in behavioral studies.

Rfamide-related peptide-3 suppresses the substance P-induced promotion of the reproductive performance in female rats modulating hypothalamic Kisspeptin expression.

RFamide-related peptide-3 (RFRP-3) has been postulated as the suppressor of the reproductive axis at hypothalamic, pituitary and gonadal levels. Considering the hypothalamic level, RFRP-3 can suppress the activity of gonadotropin-releasing hormone (GnRH) neurons and their upstream neuronal stimulator, namely; the kisspeptin neurons. The effects of the RFRP-3 on the other regulators of GnRH neurons, however, are not completely investigated. Furthermore, substance P (SP) has been known as one of the coordinators of GnRH/ luteinizing hormone (LH) and the kisspeptin/G protein-coupled receptor 54 (GPR54) systems. The present study was aimed at investigating the impacts of RFRP-3 on the effects of SP on the reproductive performance in ovariectomized female rats. After intracerebroventricular (ICV) cannulation, the rats were subjected to the ICV injection of either SP or RFRP-3 and simultaneous injection of them and their selective antagonists. Blood and hypothalamic samplings and also sexual behavioral test were carried out on two main groups of rats. The analyses of the results of LH radioimmunoassay, gene expression assay for hypothalamic Gnrh1, Kisspeptin and Gpr54 accompanied by sexual behavioral examination revealed that the SP administration promotes reproductive behavior and GnRH/LH system and upregulates Kisspeptin expression. The RFRP-3 administration suppressed reproductive behavior, GnRH / LH system and Kisspeptin expression; however, the simultaneous injection of SP and RFRP-3 was devoid of significant alterations in the assessed parameters. The results showed that RFRP-3 can modulates the impacts of SP on the reproductive performance in ovariectomized female rats in part through adjusting Kisspeptin expression.

Sexually dimorphic responses of rats to fluoxetine in the forced swimming test are unrelated to the function of the serotonin transporter in the brain

Due to the prevalence of depression in women, female rats may be a better models for antidepressant research than males. In male rats, fluoxetine inhibited the serotonin (5-hydroxytryptamine, 5-HT) transporter (SERT) which is reducing the immobility time in the repeated forced swimming test (rFST). The performance of female rats in this test is unknown. In this study, responses of male and female rats in the rFST under chronic treatment with fluoxetine and the function of SERT in their brains were examined. Wistar rats received oral fluoxetine (females: 0, 1, 2.5, or 5mgkg-1 day-1 ; males: 0 or 2.5mgkg-1 day-1 ; in sucrose 10%, 1.5ml/rat) 1 hr before the test daily for 12days over the course of the rFST. rFST consisted of a 15 min pretest followed by 5 min sessions of swimming at 1 (test), 7 (retest 1), and 14 (retest 2) days later. SERT functioning was assessed by ex vivo assays of the frontal cortex and hippocampus of rats. Fluoxetine reduced immobility time of males in the rFST while it failed to do so in females. In vitro treatment with fluoxetine inhibited the uptake of 5-HT of both sexes similarly, while in vivo chronic administration of fluoxetine failed to do so. In summary, rats responded to the chronic treatment with fluoxetine in a sexually dimorphic fashion during the rFST despite the functioning of SERT in their brains remaining equally unchanged. Hence, our data suggest that sexually dimorphic responses to fluoxetine in rFST may be unrelated to the function of SERT in rat brains.

Consequences of Adolescent Exposure to the Cannabinoid Receptor Agonist WIN55,212-2 on Working Memory in Female Rats.

Marijuana is a prevalent illicit substance used by adolescents, and several studies have indicated that adolescent use can lead to long-term cognitive deficits including problems with attention and memory. However, preclinical animal studies that observe cognitive deficits after cannabinoid exposure during adolescence utilize experimenter administration of doses of cannabinoids that may exceed what an organism would choose to take, suggesting that contingency and dose are critical factors that need to be addressed in translational models of consequences of cannabinoid exposure. Indeed, we recently developed an adolescent cannabinoid self-administration paradigm in male rats, and found that prior adolescent self-administration of the cannabinoid receptor agonist WIN55,212-2 (WIN) resulted in improved working memory performance in adulthood. In addition, the doses self-administered were not as high as those that are found to produce memory deficits. However, given known sex differences in both drug self-administration and learning and memory processes, it is possible that cannabinoid self-administration could have different cognitive consequences in females. Therefore, we aimed to explore the effects of self-administered vs. experimenter-administered WIN in adolescent female rats on adult cognitive function. Female rats were trained to self-administer WIN daily throughout adolescence (postnatal day 34–59). A control group self-administered vehicle solution. The acute effects of adolescent WIN self-administration on memory were determined using a short-term spatial memory test 24 h after final SA session; and the long-term effects on cognitive performance were assessed during protracted abstinence in adulthood using a delayed-match-to-sample working memory task. In a separate experiment, females were given daily intraperitoneal (IP) injections of a low or high dose of WIN, corresponding to self-administered and typical experimenter-administered doses, respectively, or its vehicle during adolescence and working memory was assessed under drug-free conditions in adulthood. While self-administration of WIN in adolescence had no significant effects on short-term spatial memory or adult working memory, experimenter administration of WIN resulted in improved adult working memory performance that was more pronounced in the low dose group. Thus, low-dose adolescent WIN exposure, whether self-administered or experimenter-administered, results in either improvements or no change in adult working memory performance in female rats, similar to previous results found in males.

Sex differences in the strategies of spatial learning in prenatally-exposed rats treated with various drugs in adulthood

In the present study we investigated the sex differences in the effect of adult long-term drug treatment on cognitive functions of Wistar rats, which were prenatally exposed to MA (5mg/kg) or saline. Cognitive functions were tested as an ability of spatial learning in the Morris Water Maze (MWM), which consisted of three types of tests: “Place Navigation Test”; “Probe Test”, and “Memory Recall Test”. Adult animals were injected daily, after completion of the last trial, either with saline or cocaine (COC; 5mg/kg), MDMA (3,4-methylenedioxy-methamphetamine; 5mg/kg), morphine (MOR; 5mg/kg), or delta-9-tetrahydrocannabinol (THC; 2mg/kg). Results revealed worsened MWM performance in female rats after drug treatment in adulthood. Not only were traditionally investigated parameters affected by drug treatment (latency of platform acquisition, search strategy, distance traveled), but also strategies used by animals (thigmotaxis, scanning). Analyses of search strategies observed in the Place Navigation Test, as well as in the Memory Recall Test, demonstrated variations in the percentage of time spent in thigmotaxis and scanning in females after treatment with COC, MDMA, MOR, and THC. Although we did not see a sensitizing effect of prenatal MA, in some cases the effect of drug treatment in adulthood differed depending on the prenatal drug exposure. The data presented in this study demonstrates that exposure to drugs with various mechanisms of action alters spatial abilities of female rats in the MWM. Alterations in the effect of adult drug treatment with reference to prenatal drug exposure were also found in the present study.

Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: Potential relevance of limbic GAD

Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague–Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for 2 days and given one retention trial on the third day, with brains removed 30min later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory.

Effects of pretraining and water temperature on female rats' performance in the Morris water maze

The water maze is a complex spatial task that requires the coordination of multiple systems to perform efficiently. Various factors have been shown to influence performance in this task, including motivational state and prior experience. Although a consistent sex difference has been observed in acquiring the water maze in rats, the contribution of the various factors in female rat performance has not been fully assessed. Therefore, the current study tested the effects of motivation as manipulated by water temperature of the maze and prior experience in the maze on the performance of female rats. It was hypothesized that females pretrained in the maze would perform better than those without exposure to the water maze, regardless of water temperature, but in naïve rats, colder water would improve performance as shown previously in male rats. For pretraining, female rats were taught to find a visible platform in cold (19°C, 4 trials on one day) and warm (25°C, 4 trials on one day) water before acquisition trials, with the order of the water temperature randomly assigned. Control rats were not given any training and were naïve to the water maze procedure. Pretrained and control rats were then tested to locate a hidden platform in either cold or warm water for 5 consecutive days. Overall, pretraining had a significant effect on distance, latency, and directness of path to the platform. Water temperature did not show a significant effect on any measure or a significant interaction with pretraining. Thus, while our hypothesis that pretraining would improve performance was supported, the results did not support the prediction that water temperature would also significantly influence performance. These results show that non-spatial pretraining can critically improve the performance of females in acquiring a place strategy for the hidden platform, irrespective of water temperature.

Chronically stressed female rats show increased anxiety but no behavioral alterations in object recognition or placement memory: A preliminary examination

Stress, depending on intensity and duration, elicits adaptive or maladaptive physiological effects. Increasing evidence shows those patterns of advantageous versus deleterious physiologic stress effects also exist for some brain functions, including learning and memory. For example, short stress enhances, while chronic stress impairs, performance on numerous cognitive tasks in male rats. In contrast, performance of female rats is enhanced, or not altered, following both short-term and long-term stress exposure on the same behavioral tasks. The current study was designed to better characterize the behavioral effects of sustained chronic restraint stress in female rats. Female Sprague Dawley rats were assigned to a stress (restraint, 6 h/day, 35 days) or control (no stress) condition, weighed weekly, and then tested on open field (OF), object recognition (OR) and object placement (OP) tasks. Stressed females gained less weight during stress than controls. On the OF, there were no group differences in locomotor activity, but stressed females made fewer inner visits than controls, indicating increased anxiety. Both groups successfully performed the OP and OR tasks across all inter-trial delays, indicating intact non-spatial and spatial memory in both control and stress females. The current results provide preliminary evidence that the commonly used chronic restraint stress model may not be an efficient stressor to female rats.

P.1.g.022 Effects of intermittent cold exposure on long-term potentiation and water maze performance in female rats

P.1.g.022 Effects of intermittent cold exposure on long-term potentiation and water maze performance in female rats

Evaluation of safety margins of Chenopodium albumseed decoction: 14-day subacute toxicity and microbicidal activity studies

BackgroundSperm immobilizing activity and plausible mechanism of action of Chenopodium album seed decoction (CAD) have been elucidated in our earlier studies. The present study has been carried out to explore the safety standards of CAD along with microbicidal properties as prerequisite for its use as a topically applicable vaginal contraceptive.MethodsThe safety standards of CAD were assessed by a) Hemolytic index determination using rabbit erythrocytes, to set the doses of the other experiments, b) Dermal irritancy test using refined version of Draize scoring system on rabbits, c) Possible effect on local tissues and reproductive performance in female rats after fourteen daily single dose application, d) PCNA staining- to evaluate the effect of CAD on vaginal tissue proliferation, e) TUNEL assay- to examine its ability to induce in situ apoptosis in the vaginal tissue sections of the treated animals, and f) Microbicidal activity- to explore the effect of CAD on the growth of Lactobacillus acidophilus and Candida albicans.ResultsIn vitro irritation studies on rabbit erythrocytes revealed the hemolytic index of CAD to be 8.2 mg/ml. The dermal irritation test showed it to be a non-irritant even at higher doses. Intra vaginal application of CAD in rat vagina for 14 consecutive days caused slight reversible inflammation on vaginal epithelial cells at doses as high as 82 mg/ml. However, at this dose level it neither had any adverse effect on vaginal tissue proliferation nor did it cause in situ apoptosis as evident from PCNA staining and TUNEL assay. Fertility and fecundity were restored 4-15 days after withdrawal of CAD application. At dose level 10 times that of its spermicidal MEC (minimum effective concentration), CAD did not block the growth of Lactobacillus, although the size of individual colony was marginally reduced. However, growth of the pathogenic fungus Candida albicans was completely inhibited with 20 mg/ml of CAD.ConclusionThe overall result evolved from the study strengthens the candidature of CAD as a safe microbicidal spermicide. It is almost non-irritant to rabbit skin and rat vaginal tissues at doses 10 fold higher than its hemolytic index. The effect of CAD on Lactobacillus culture was not highly encouraging but it prevented the growth of the fungal pathogen Candida albicans at 20 mg/ml of CAD.

Enhanced Learning Deficits in Female Rats Following Lifetime Pb Exposure Combined with Prenatal Stress

Pb (lead) exposure and stress are co-occurring risk factors (particularly in low socioeconomic communities) that also act on common biological substrates and produce common adverse outcomes, including cognitive impairments. This study sought to determine whether lifetime Pb exposure combined with prenatal stress would enhance the cognitive deficits independently associated with each of these risk factors and to explore associated mechanisms of any observed impairments. Learning was evaluated using a multiple schedule of repeated learning and performance in female rats subjected to lifetime Pb exposure (0 or 50 ppm Pb in drinking water beginning in dams 2 months prior to breeding; blood Pb levels ∼10 μg/dl), to prenatal restraint stress on gestational days 16 and 17, or to both. Blood Pb, corticosterone levels, brain monoamines, and hippocampal nerve growth factor levels were also measured. Sequence-specific learning deficits produced by Pb, particularly the number of responses to correctly learn response sequences, were further enhanced by stress, whereas performance measures were unimpaired. Statistical analyses indicated significant relationships among corticosterone levels, frontal cortex dopamine (DA), nucleus accumbens dopamine turnover, and total responses required to learn sequences. This study demonstrates that Pb and stress can act together to produce selective and highly condition-dependent deficits in learning in female rats that may be related to glucocorticoid-mediated interactions with mesocorticolimbic regions of brain. These findings also underscore the critical need to evaluate toxicants in the context of other risk factors pertinent to human diseases and disorders.

Root Extract of Polygonum Hydropiper Alters the Expression of Rat Uterine Protein Profile in Presence and Absence of Ovary in-situ during Periimplantation Period: An Evidence on SDS-PAGE

Objective To study its effects on reproductive performance in albino rats. Methods The chromatographic fraction (CF) of crude methanolic extract of the herb has been subcutaneously administered to female albino rats. Experiments were carried out in adult cyclic females and oavriectomised (OVX) females during early gestation period. Uterine horns were collected following the respective treatment regimen to study the protein profile in 15% gel SDS-PAGE. Results The CF induced changes in the expression of protein in rat uterus. New proteins have been expressed in uterus of adult cyclic females having ovary in-situ. The OVX females treated with CF showed altered uterine protein profile compared with that of OVX control and OVX estradiol-17β (E2) treated rats. The CF exerted its effect on expression of uterine protein during early gestation period in rats. While uterine proteins of CF treated females were similar to that of controls during preimplantation period; many of the proteins on day 6 of gestation have been found either missing or expressed in lesser intensity. Conclusion The root of Polygonum hydropiper contains potential compound(s) which can alter the reproductive performance of female rats modulating uterine protein expression.

Isolation rearing impairs novel object recognition and attentional set shifting performance in female rats

It has been suggested that the isolation rearing paradigm models certain aspects of schizophrenia symptomatology. This study aimed to investigate whether isolation rearing impairs rats' performance in two models of cognition: the novel object recognition (NOR) and attentional set-shifting tasks, tests of episodic memory and executive function, respectively. Two cohorts of female Hooded-Lister rats were used in these experiments. Animals were housed in social isolation or in groups of five from weaning, post-natal day 28. The first cohort was tested in the NOR test with inter-trial intervals (ITIs) of 1 min up to 6 h. The second cohort was trained and tested in the attentional set-shifting task. In the NOR test, isolates were only able to discriminate between the novel and familiar objects up to 1-h ITI, whereas socially reared animals remembered the familiar object up to a 4-h ITI. In the attentional set-shifting task, isolates were significantly and selectively impaired in the extra-dimensional shift phase of the task (P < 0.01). Rats reared in isolation show impaired episodic memory in the NOR task and reduced ability to shift attention between stimulus dimensions in the attentional set-shifting task. Because schizophrenic patients show similar deficits in performance in these cognitive domains, these data further support isolation rearing as a putative preclinical model of the cognitive deficits associated with schizophrenia.

Sex differences in the long-term effect of preweanling isolation stress on memory retention

Social experiences during development can powerfully modulate later neuroendocrine and behavioral system. In the present study, male and female rat pups experienced daily bouts of social isolation for 6 h per day or control conditions during the third postnatal week. Performance on a 12-arm radial maze with 8 arms consistently baited with food reward was examined in adulthood. During the social isolation, both male and female pups exhibited a significant increase in plasma corticosterone levels. When tested on the radial arm maze as adults, the performance of female rats that had experienced social isolation during development was not affected; however, male rats in the isolation condition initially exhibited impairments in working memory but not reference memory. Despite achieving comparable asymptotic levels of performance on the maze, male rats that experienced social isolation during the third week demonstrated disruption in working memory retention when radial arm maze trials were interrupted after the fourth arm choice. Thus, while male rats that experience social isolation during the third week of life eventually perform comparably to controls on the standard radial arm maze task, their ability to retain information over a delay remains impaired. These findings highlight an important sex difference in the long-term effects of stress during this period of late preweanling development.