scholarly journals Behavior and Fos activation reveal that male and female rats differentially assess affective valence during CTA learning and expression

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260577
Author(s):  
Alyssa Bernanke ◽  
Elizabeth Burnette ◽  
Justine Murphy ◽  
Nathaniel Hernandez ◽  
Sara Zimmerman ◽  
...  
Keyword(s):  
Sex Differences ◽  
D2 Receptor ◽  
Brain Regions ◽  
D1 Receptor ◽  
Neural Mechanisms ◽  
Female Rats ◽  
Post Traumatic Stress ◽  
Affective Valence ◽  
Male And Female Rats ◽  
Males And Females

Females are more affected by psychiatric illnesses including eating disorders, depression, and post-traumatic stress disorder than males. However, the neural mechanisms mediating these sex differences are poorly understood. Animal models can be useful in exploring such neural mechanisms. Conditioned taste aversion (CTA) is a behavioral task that assesses how animals process the competition between associated reinforcing and aversive stimuli in subsequent task performance, a process critical to healthy behavior in many domains. The purpose of the present study was to identify sex differences in this behavior and associated neural responses. We hypothesized that females would value the rewarding stimulus (Boost®) relative to the aversive stimulus (LiCl) more than males in performing CTA. We evaluated behavior (Boost® intake, LiCl-induced behaviors, ultrasonic vocalizations (USVs), CTA performance) and Fos activation in relevant brain regions after the acute stimuli [acute Boost® (AB), acute LiCl (AL)] and the context-only task control (COT), Boost® only task (BOT) and Boost®-LiCl task (BLT). Acutely, females drank more Boost® than males but showed similar aversive behaviors after LiCl. Females and males performed CTA similarly. Both sexes produced 55 kHz USVs anticipating BOT and inhibited these calls in the BLT. However, more females emitted both 22 kHz and 55 kHz USVs in the BLT than males: the latter correlated with less CTA. Estrous cycle stage also influenced 55 kHz USVs. Fos responses were similar in males and females after AB or AL. Females engaged the gustatory cortex and ventral tegmental area (VTA) more than males during the BOT and males engaged the amygdala more than females in both the BOT and BLT. Network analysis of correlated Fos responses across brain regions identified two unique networks characterizing the BOT and BLT, in both of which the VTA played a central role. In situ hybridization with RNAscope identified a population of D1-receptor expressing cells in the CeA that responded to Boost® and D2 receptor-expressing cells that responded to LiCl. The present study suggests that males and females differentially process the affective valence of a stimulus to produce the same goal-directed behavior.

scholarly journals Stem cell treatment improves post stroke neurological outcomes: a comparative study in male and female rats

2021 ◽  
pp. svn-2020-000834
Author(s):  
Koteswara Rao Nalamolu ◽  
Bharath Chelluboina ◽  
Casimir A Fornal ◽  
Siva Reddy Challa ◽  
David M Pinson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Sex Differences ◽  
Motor Function ◽  
Infarct Volume ◽  
Female Rats ◽  
Human Umbilical Cord ◽  
Male And Female ◽  
Post Stroke ◽  
Male And Female Rats ◽  
Males And Females

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.

scholarly journals Sex Differences and Similarities in Hippocampal Cellular Proliferation and the Number of Immature Neurons during Adolescence in Rats

2019 ◽  
Vol 41 (1-2) ◽  
pp. 132-138 ◽  
Author(s):  
Alina Siddiqui ◽  
Russell D. Romeo
Keyword(s):  
Sex Differences ◽  
Dentate Gyrus ◽  
Cellular Proliferation ◽  
Female Rats ◽  
Male Rats ◽  
Ki 67 ◽  
Cross Sectional ◽  
Male And Female Rats ◽  
Immature Neurons ◽  
Males And Females

Adolescence is associated with significant reductions in hippocampal cellular proliferation and neurogenesis, the physiological and behavioral implications of which are unclear. Though sex differences exist in these proliferative processes in adulthood, relatively little is known about the role sex plays in these adolescent-related changes. To address this gap, we examined cross-sectional area of the dentate gyrus and cellular proliferation, as measured by Ki-67 immunohistochemistry, in pre- (30 days), mid- (45 days), and post-adolescent (70 days) male and female rats. We also investigated the number of immature neurons using doublecortin (DCX) immunohistochemistry in pre- and post-adolescent males and females. Despite increases in the size of the dentate gyrus during adolescence, we found significant adolescent-related decreases in hippocampal proliferation in both males and females, with a more dramatic decrease in males, indicating both age- and sex-dependent changes in the dentate gyrus. We also found an adolescent-related decline in the number of immature neurons in the dentate gyrus of male rats and a female-biased sex difference in the number of immature neurons in adults. Given these significant changes in the dentate gyrus, these data suggest that this period in development might be particularly sensitive to internal and external factors known to modulate neurogenesis, with potential sex-specific neurobehavioral ramifications.

scholarly journals Sex differences in traumatic stress reactivity of rats with a history of alcohol drinking

2019 ◽  
Author(s):  
Lucas Albrechet-Souza ◽  
Connor L. Schratz ◽  
Nicholas W. Gilpin
Keyword(s):  
Sex Differences ◽  
Traumatic Stress ◽  
Alcohol Drinking ◽  
Stress Reactivity ◽  
Acoustic Startle ◽  
Predator Odor ◽  
Female Rats ◽  
Post Traumatic Stress ◽  
Male And Female Rats ◽  
Odor Exposure

AbstractBackgroundAlcohol misuse and post-traumatic stress disorder (PTSD) are highly comorbid and treatment outcomes are worse in individuals with both conditions. Although more men report experiencing traumatic events than women, the lifetime prevalence of PTSD is twice as high in females. Despite these data trends in humans, preclinical studies of traumatic stress reactivity have been performed almost exclusively in male animals.MethodsThis study was designed to examine sex differences in traumatic stress reactivity in alcohol-naïve rats and rats given intermittent access to 20% ethanol in a 2-bottle choice paradigm for 5 weeks. Rats were exposed to predator odor (bobcat urine) and tested for avoidance of the odor-paired context 24 hours later; unstressed Controls were never exposed to odor. Two days after stress, we measured physiological arousal using the acoustic startle response (ASR) test. We also measured anxiety-like behavior using the elevated plus-maze (EPM) and circulating corticosterone levels before and immediately after odor exposure.ResultsMale and female rats exposed to predator odor displayed blunted weight gain 24 hours post-stress, but only a subset of stressed animals exhibited avoidance behavior. Chronic intermittent alcohol drinking increased the proportion of Avoiders in males and predator odor exposure increased ASR in these animals. Predator odor stress reduced ASR in females relative to unstressed females and stressed males, regardless of alcohol drinking history. Bobcat urine exposure did not promote persistent anxiety-like behavior, but alcohol-experienced males exhibited reduced activity in the EPM in comparison to alcohol-experienced females.Furthermore, predator odor increased circulating corticosterone levels in females relative to males and baseline.ConclusionsWe report robust sex differences in behavioral and endocrine responses to bobcat urine exposure in adult Wistar rats. Also, chronic moderate alcohol drinking increased traumatic stress reactivity in males but not females. Our findings emphasize the importance of considering sex as a biological variable in the investigation of traumatic stress effects on physiology and behavior.

scholarly journals Dopamine D1 and D2 Receptors Are Important for Learning About Neutral-Valence Relationships in Sensory Preconditioning

2021 ◽  
Vol 15 ◽  
Author(s):  
Stephanie Roughley ◽  
Abigail Marcus ◽  
Simon Killcross
Keyword(s):  
D2 Receptor ◽  
Female Rats ◽  
Sensory Preconditioning ◽  
Affective Valence ◽  
Sensory Stimuli ◽  
D1 And D2 Receptors ◽  
Male And Female Rats ◽  
Dopaminergic Systems ◽  
Series Of Experiments

Dopamine neurotransmission has been ascribed multiple functions with respect to both motivational and associative processes in reward-based learning, though these have proven difficult to tease apart. In order to better describe the role of dopamine in associative learning, this series of experiments examined the potential of dopamine D1- and D2-receptor antagonism (or combined antagonism) to influence the ability of rats to learn neutral valence stimulus-stimulus associations. Using a sensory preconditioning task, rats were first exposed to pairings of two neutral stimuli (S2-S1). Subsequently, S1 was paired with a mild foot-shock and resulting fear to both S1 (directly conditioned) and S2 (preconditioned) was examined. Initial experiments demonstrated the validity of the procedure in that measures of sensory preconditioning were shown to be contingent on pairings of the two sensory stimuli. Subsequent experiments indicated that systemic administration of dopamine D1- or D2-receptor antagonists attenuated learning when administered prior to S2-S1 pairings. However, the administration of a more generic D1R/D2R antagonist was without effect. These effects remained constant regardless of the affective valence of the conditioning environment and did not differ between male and female rats. The results are discussed in the context of recent suggestions that dopaminergic systems encode more than a simple reward prediction error, and provide potential avenues for future investigation.

scholarly journals Sex-specific effects of neonatal progestin receptor antagonism on juvenile social behavior in rats.

2021 ◽  
Author(s):  
Robin M Forbes-Lorman
Keyword(s):  
Sex Differences ◽  
Brain Regions ◽  
Female Rats ◽  
Male Rats ◽  
Postnatal Life ◽  
Social Discrimination ◽  
Specific Effects ◽  
Male And Female Rats ◽  
Brain And Behavior

Abstract Developing mammals are exposed to progesterone through several sources; however, the role of progesterone in early development is not well understood. Males express more progestin receptors (PRs) than females within several brain regions during early postnatal life, suggesting that PRs may be important for the organization of the sex differences in the brain and behavior. Indeed, previous studies showed cognitive impairments in male rats treated neonatally with a PR antagonist. In the present study, we examined the role of PRs in organizing juvenile behaviors. Social play behavior and social discrimination were examined in juvenile male and female rats that had been treated with CDB, a PR antagonist, during the first week of postnatal life. Interestingly, neonatal PR antagonism altered different juvenile behaviors in males and females. A transient disruption in PR signaling during development had no effect on social discrimination but increased play initiation and pins in females. These data suggest that PRs play an important role in the organization of sex differences in some social behaviors.

GONADOTROPHIN PATTERNS IN MALE AND FEMALE RATS:

1968 ◽  
Vol 58 (4) ◽  
pp. 600-612 ◽  
Author(s):  
Robert Boyd ◽  
Donald C. Johnson
Keyword(s):  
Ascorbic Acid ◽  
Testosterone Propionate ◽  
Female Rats ◽  
Female Rat ◽  
Feedback Effects ◽  
Male And Female ◽  
Prostate Weight ◽  
Male And Female Rats ◽  
Males And Females ◽  
Normal Males

ABSTRACT The effects of various doses of testosterone propionate (TP) upon the release of luteinizing hormone (LH or ICSH) from the hypophysis of a gonadectomized male or female rat were compared. Prostate weight in hypophysectomized male parabiotic partners was used to evaluate the quantity of circulating LH. Hypophyseal LH was measured by the ovarian ascorbic acid depletion method. Males castrated when 45 days old secreted significantly more LH and had three times the amount of pituitary LH as ovariectomized females. Administration of 25 μg TP daily reduced the amount of LH in the plasma, and increased the amount in the pituitary gland, in both sexes. Treatment with 50 μg caused a further reduction in plasma LH in males, but not in females, while pituitary levels in both were equal to that of their respective controls. LH fell to the same low level in partners of males or females receiving 100 μg TP. When gonadectomized at 39 days, males and females had the same amount of plasma LH, but males had more stored hormone. Pituitary levels were unchanged from controls following treatment with 12.5, 25 or 50 μg TP daily, but plasma values dropped an equal amount in both sexes with the latter two doses. Androgenized males or females, gonadectomized when 39 days old, were very sensitive to the effects of TP and plasma LH was significantly reduced with 12.5 μg daily. Pituitary LH in androgenized males was higher than that of normal males but was reduced to normal by small amounts of TP. The amount of stored LH in androgenized females was not different from that of normal females and it was unchanged by any dose of TP tested. Results are consistent with the conclusion that the male hypothalamic-hypophyseal axis is at least as sensitive as the female axis to the negative feedback effects of TP. Androgenization increases the sensitivity to TP in both males and females.

scholarly journals Analysis of sex differences in dietary copper-fructose interaction-induced alterations of gut microbial activity in relation to hepatic steatosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Song ◽  
Fang Yuan ◽  
Xiaohong Li ◽  
Xipeng Ma ◽  
Xinmin Yin ◽  
...  
Keyword(s):  
Sex Differences ◽  
Microbial Activity ◽  
Hepatic Steatosis ◽  
Female Rats ◽  
Male Rats ◽  
Calorie Intake ◽  
Dietary Copper ◽  
Male And Female ◽  
Male And Female Rats ◽  
Rrna Sequencing

Abstract Background Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. Methods Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6 mg/kg and 1.5 mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma alanine aminotransferase, aspartate aminotransferase, and liver histology as well as liver triglyceride were evaluated. Fecal microbial contents were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Fecal and cecal short-chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS). Results Male and female rats exhibit similar trends of changes in the body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in the CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF diets. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. Conclusions Our data demonstrated sex differences in the alterations of gut microbial abundance, activities, and hepatic steatosis in response to dietary copper-fructose interaction in rats. The correlation between sex differences in metabolic phenotypes and alterations of gut microbial activities remains elusive.

scholarly journals Vulnerability factors for mephedrone-induced conditioned place preference in rats—the impact of sex differences, social-conditioning and stress

2021 ◽  
Author(s):  
Olga Wronikowska ◽  
Maria Zykubek ◽  
Łukasz Kurach ◽  
Agnieszka Michalak ◽  
Anna Boguszewska-Czubara ◽  
...  
Keyword(s):  
Sex Differences ◽  
Conditioned Place Preference ◽  
Low Dose ◽  
Social Factor ◽  
Place Preference ◽  
Female Rats ◽  
Male Rats ◽  
Social Conditioning ◽  
Male And Female Rats ◽  
The Impact

Abstract Rationale Mephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood. Objectives The aim of the presented study was to assess the impact of several factors (sex differences, social-conditioning, and chronic mild unpredictable stress — CMUS) on the liability to mephedrone-induced reward in Wistar rats. Methods The rewarding effects of mephedrone in male and female rats were assessed using the conditioned place preference (CPP) procedure. Furthermore, the impact of social factor and stress was evaluated in male rats using social-CPP and CMUS-dependent CPP, respectively. Results Mephedrone induced classic-CPP in female (10 mg/kg), as well as in male (10 and 20 mg/kg) rats. However, the impact of mephedrone treatment during social-CPP was highly dose-dependent as the rewarding effects of low dose of mephedrone (5 mg/kg; non-active in classic-CPP) were potentiated when administered during social-conditioning. Interestingly, social-conditioning with a higher dose of 20 mg/kg (that induced classic-CPP) was able to reverse these effects. Finally, CMUS potentiated rewarding effects of a low dose of mephedrone (5 mg/kg) and increased the level of corticosterone in rats’ prefrontal cortex and hippocampus. Conclusions Altogether, the presented results give new insight into possible factors underlying the vulnerability to mephedrone abuse and can serve as a basis for further studies assessing mechanisms underlying observed effects.

scholarly journals Sex Differences in Escalated Methamphetamine Self-Administration and Altered Gene Expression Associated With Incubation of Methamphetamine Seeking

2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  
Keyword(s):  
Sex Differences ◽  
Nucleus Accumbens ◽  
Fixed Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Self Administration ◽  
Male And Female ◽  
Orexin Receptors ◽  
Male And Female Rats

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.

Gonadal steroids effect similar regulation of gonadotrophin subunit mRNA expression in both male and female rats

1992 ◽  
Vol 132 (1) ◽  
pp. 39-45 ◽  
Author(s):  
A. C. Dalkin ◽  
S. J. Paul ◽  
D. J. Haisenleder ◽  
G. A. Ortolano ◽  
M. Yasin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Steady State ◽  
Gnrh Antagonist ◽  
Gonadal Steroids ◽  
Female Rats ◽  
Plasma Testosterone ◽  
Subunit Gene ◽  
Gnrh Secretion ◽  
Male And Female Rats ◽  
Males And Females

ABSTRACT Gonadal steroids can act both indirectly via gonadotrophin-releasing hormone (GnRH) and directly on the pituitary to regulate gonadotrophin subunit gene expression. Recent studies to assess a possible direct action at the pituitary have shown that testosterone, when given to males in the absence of endogenous GnRH action, selectively increases FSH-β mRNA concentrations. Conversely, in females, oestradiol appears to regulate gonadotrophin subunit mRNAs primarily via GnRH. The present study was designed to determine whether these differing results reflect specific actions of the gonadal steroids themselves or different responses of the pituitary gonadotroph cells in males and females. Rats which had been castrated 7 days earlier were given silicone elastomer implants (s.c.) containing oestradiol (plasma oestradiol 68 ± 4 ng/l) in males or testosterone (plasma testosterone 3·5 ± 0·3 μg/l) in females in the absence or presence of a GnRH antagonist. Seven days later pituitaries were removed and steady-state mRNA concentrations measured by dotblot hybridization. In males, oestradiol reduced LH-β and FSH-β but not α mRNA. The antagonist reduced levels of all three subunit mRNAs in males and the addition of oestradiol had no further effect, suggesting that oestradiol regulates gonadotrophin subunit gene expression in males by suppressing GnRH secretion. In females, testosterone reduced all three subunit mRNAs though FSH-β remained threefold higher than in intact animals. The GnRH antagonist was as effective as testosterone alone and reduced α and LH-β to levels found in intact animals. FSH-β mRNA was partially reduced by antagonist alone in ovariectomized females but the addition of testosterone increased FSH-β twofold versus antagonist alone (as has been observed in males). These findings, together with earlier data, suggest that testosterone increased FSH-β twofold versus antagonist alone (as has been observed in males). These findings, together with earlier data, suggest that testosterone reduces gonadotrophin subunit mRNAs by inhibiting GnRH secretion and also acts directly on the gonadotroph to increase steady-state FSH-β mRNA concentrations in both males and females. Journal of Endocrinology (1992) 132, 39–45

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