Responses Of Male Rats Research Articles

Predator odor exposure in early adolescence influences the effects of the bacterial product, propionic acid, on anxiety, sensorimotor gating, and acoustic startle response in male rats in later adolescence and adulthood

It is becoming evident than the adolescent period is a sensitive period in stress response programming. Stressors during this time may alter signaling from the gut microbiome, which has been shown to increase the risk for psychiatric disorders. It was hypothesized that adolescent stressors may potentiate the symptoms of anxiety and sensory abnormalities induced by a gut bacterial product, the short-chain fatty acid, propionic acid (PPA). The present study investigated the effects of repeated predator odor exposure during early adolescence on male rats administered PPA in late adolescence and adulthood on a behavioral test battery. Male adolescent Long-Evans rats were repeatedly exposed to a worn or unworn cat collar stimulus in early adolescence on postnatal days (P) 28, P30, P32, and P34. They were administered either PPA (500 mg/kg i.p.), or its vehicle in late adolescence on P40 and P43, and were subsequently tested on the light-dark anxiety task and acoustic startle task, respectively. In adulthood, the rats were again injected with PPA or its vehicle on P74 and P77, and subsequently tested on the light-dark apparatus and acoustic startle task, respectively. The repeated predator odor exposure was aversive and produced long-term anxiogenic effects as measured by the light-dark apparatus. PPA decreased activity and percent prepulse inhibition of the acoustic startle response, with its effects on vertical activity, a putative measure of escape behavior, being potentiated by prior predator stress. PPA's effects in adulthood were diminished in comparison to adolescence. These results suggest the importance of evaluating the effects of early adolescent stress on subsequent environmental insults on the development of behavioral abnormalities.

Sexual activity modulates neuroinflammatory responses in male rats

Immune activity influences reproduction, however, the extent to which mating experience may inversely alter immune pathways is poorly understood. A few studies in humans suggest that mating triggers a circulating immune and hypothalamic-pituitary-adrenal axis response. In male rats, mating experience enhances neuroplasticity and improves cognitive function and affective-like behavior, independent of the physical activity component. Yet, the extent to which mating experience may influence immune responses in the brain remain unexplored. Here, we hypothesized that recent mating experience in male rats increases neuroinflammatory signaling (via lipopolysaccharide [LPS] stimulation, i.p.) and associated sickness behaviors (i.e., food intake, weight loss) relative to sexually-naïve controls. Virgin male rats were exposed to a sexually non-receptive (control) or sexually-receptive female for 30 min for six consecutive days. Immediately following the last mating experience, rats were administered a saline or LPS injection and euthanized four hours later. Mating increased Tnfα responses to LPS in the brain, which positively correlated with LPS-induced weight loss. Mating also increased peripheral corticosterone among saline-treated rats, but this corticosterone response was attenuated in the most proficient copulators (e.g., shortest latencies). Thus, recent mating experience may be a unique modulator of select stimulated inflammatory signals that are relevant to adaptive neuroimmune responses and behavior.

Challenges to Body Fluid Homeostasis Differentially Recruit Phasic Dopamine Signaling in a Taste-Selective Manner.

The internal environment of an organism must remain stable to ensure optimal performance and ultimately survival. The generation of motivated behaviors is an adaptive mechanism for defending homeostasis. Although physiological state modulates motivated behaviors, the influence of physiological state on phasic dopamine signaling, an underlying neurobiological substrate of reward-driven behavior, is underexplored. Here, we use sodium depletion and water restriction, manipulations of body fluid homeostasis, to determine the flexibility and specificity of dopamine responses. Changes in dopamine concentration were measured using fast-scan cyclic voltammetry in the nucleus accumbens shell of male rats in response to intraoral infusions of fluids that either satisfied or did not satisfy homeostatic need. Increases in dopamine concentration during intraoral infusions were observed only under conditions of physiological deficit. Furthermore, dopamine increases were selective and limited to those that satisfied the need state of the animal. Thus, dopamine neurons track fluid balance and respond to salt and water stimuli in a state- and taste-dependent manner. Using Fluoro-Gold tracing and immunohistochemistry for c-Fos and Foxp2, a marker of sodium-deprivation responsive neurons, we revealed brainstem populations of neurons that are activated by sodium depletion and project directly to the ventral tegmental area. The identified projections may modulate dopamine neuron excitability and consequently the state-specific dopamine release observed in our experiments. This work illustrates the impact of physiological state on mesolimbic dopamine signaling and a potential circuit by which homeostatic disruptions are communicated to mesolimbic circuitry to drive the selective reinforcement of biologically-required stimuli under conditions of physiological need.SIGNIFICANCE STATEMENT Motivated behaviors arise during physiological need and are highly selective for homeostasis-restoring stimuli. Although phasic dopamine signaling has been shown to contribute to the generation of motivated behaviors, the state and stimulus specificity of phasic dopamine signaling is less clear. These studies use thirst and sodium appetite to show that dopamine neurons dynamically track body fluid homeostasis and respond to water and salt stimuli in a state- and taste-dependent manner. We also identify hindbrain sodium deprivation-responsive neurons that project directly to the ventral tegmental area, where dopamine neuron cell bodies reside. This work demonstrates command of homeostasis over dopamine signaling and proposes a circuit by which physiological need drives motivated behavior by state- and taste-selective recruitment of phasic dopamine signaling.

ACUTE EXPOSURE TO NANO‐TIO2 PARTICLES CAUSES SEVERE ENDOTHELIUM‐ DEPENDENT DYSFUNCTION IN THE MIDDLE CEREBRAL ARTERY

BackgroundThe use of engineered nanomaterials (ENM) is increasing; however, proper EMN toxicological assessments are typically incomplete. Previous studies demonstrate that ENM exposure is linked to adverse cardiovascular outcomes, including stroke. The cerebral microcirculation is key in regulating cerebral blood flow and any dysfunction may increase the risk of stroke. The direct impact of exposure to nano‐titanium dioxide (TiO2) on cerebral microvasculature is unknown.MethodsTo determine whether acute nano‐TiO2 exposure causes cerebral endothelial dysfunction, intratracheal instillation was used to deliver 240 μg of TiO2 suspended in 300 μl of sterile PBS vehicle to male and female Sprague‐Dawley rats 24 hours prior to surgery. The middle cerebral arteries (MCAs) were isolated and hung in a pressurized myobath. To assess endothelial‐dependent function, MCAs were challenged with increasing doses of acetylcholine (ACh; endo dependent dilation) and phenylephrine (PE; α‐adrenergic‐mediated constrictor). As endothelial dysfunction can be caused by oxidative stress, possibly through increased xanthine oxidase activity. To explore this, MCAs were incubated with Febuxostat (10 μM), a xanthine oxidase inhibitor, for 30 mins prior to treatment with Ach. To examine the effects of oxidative stress on MCA function we then exposed MCAs to the XO‐specific inhibitor, febuxostat (10 μM) for 30 min prior to ACh‐induced dilation.ResultsTiO2 exposure decreased MCA endothelium‐dependent dilation (p<0.05) in both sexes. However, febuxostat treatment restored the impaired dilation response in male rats, whereas no effect was observed in females. Interestingly, PE‐induced constriction of MCAs was also attenuated (p<0.05) in rats exposed to nano‐TiO2 compared to controls, suggesting overall MCA function was significantly decreased with nano‐TiO2 exposure.ConclusionThese data provide evidence that acute exposure to nano‐TiO2 significantly impairs MCA endothelium‐dependent dilation and constriction. However, incubation with a XO inhibitor limits this dysfunction but only in males, suggesting 1) a contributory role for XO in mediating TiO2 toxicity in the vasculature, and 2) an interesting sex‐related difference in the compromised cerebral microvascular health after nano‐TiO2 exposure. Experiments are underway to discover the underlying mechanism(s) that contribute to these observations.Support or Funding InformationNIH ES015022 (TRN); NIHGMS 1P20 GM‐109098 (PDC), AHA 16PRE30820000 (ED)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Voluntary physical activity counteracts the proliferative tumor growth microenvironment created by adipose tissue via high-fat diet feeding in female rats

The adipokine secretion profile created from adipose tissue may represent the molecular mechanism behind the obesity‐breast cancer association. Two adipokines, adiponectin (ADIPO), and leptin (LEP), are altered with obesity and exert antagonistic effects on breast cancer proliferation. We set out to determine whether the adipose‐dependent tumor promoting growth environment created by a high‐fat diet (HFD) in female Sprague‐Dawley rats is altered compared to established responses in male rats and whether voluntary physical activity (PA) ameliorates any HFD‐dependent effects. We found that conditioned media (CM) created from the adipose tissue of female HFD‐fed rats increased the proliferation of MCF7 cells compared to those cells grown in CM prepared from lean adipose tissue. HFD‐CM inhibited AMPK and activated Akt signaling, decreased p27 phosphorylation at T198, reduced total p27 and AdiporR1 protein levels and promoted cell‐cycle entry. PA reversed the proliferative effects of HFD‐CM on MCF7 cells by preventing the effects of HFD on AMPK, Akt, p27 and AdipoR1, ultimately resulting in cell‐cycle withdrawal. Overexpressing AdipoR1 abolished the proliferative effects of the HFD‐CM on MCF7 cells and enhanced the anti‐proliferative effects PA on the HFD‐CM. Thus, PA represents a means to prevent deleterious obesity‐related alterations in tumor growth environment which are brought about by changes in adipokine secretion profile from adipose tissue in the presence of estrogen. Furthermore, although adipose produces hundreds of adipokines, the ADIPO:LEP ratio may serve to indicate the contribution of adipose in creating a tumor growth microenvironment.

High-monosaccharide intake inhibits anorexigenic hypothalamic insulin response in male rats

Objective: The aim of this research is to evaluate if intake of 20% fructose solution is able to change the anorexigenic hypothalamic insulin action.Methods: Thirty day-old male Wistar rats were randomly assigned to one of the following groups: standard chow and water for the rats (Control group, C) and standard chow and 20% fructose solution for the rats (Fructose group, F).These treatments lasted 8 weeks. Three-month-old rats from group C and F received insulin or saline intracerebroventricular injections for evaluation of 24 h food intake, phosphorylated forms of the IR (p-IR) and Akt (p-Akt) proteins and quantified hypothalamic insulin receptor (IR) and insulin receptor substrate 1 (IRS-1) proteins.Results: Insulin injection was able to decrease food intake in group C compared to 0.9% saline. However, insulin infusion failed to inhibit 24 h food intake in group F compared to 0.9% saline. The hypothalamic content of the IRS-1 was 37% higher in group F as well as p-Akt protein was significant higher vs. group C.Conclusion: We concluded that the 20% fructose solution compromised insulin signaling considering that it inhibited the anorexigenic hypothalamic response to acute injection of this hormone and increase of IRS-1 and p-Akt content.

A mixed glucocorticoid/mineralocorticoid receptor modulator dampens endocrine and hippocampal stress responsivity in male rats

Aberrant glucocorticoid secretion is implicated in the pathophysiology of stress-related disorders (i.e., depression, anxiety). Glucocorticoids exert biological effects via mineralocorticoid (MR) and glucocorticoid (GR) receptors. Previous data from our laboratory indicate that GR antagonism/modulation (i.e., mifepristone, CORT 108297) regulate endocrine, behavioral, and central stress responses. Because of the dynamic interplay between MR and GR on HPA axis regulation and emotionality, compounds targeting both receptors are of interest for stress-related pathology. We investigated the effects of CORT 118335 (a dual selective GR modulator/MR antagonist) on endocrine, behavioral, and central (c-Fos) stress responses in male rats. Rats were treated for five days with CORT 118335, imipramine (positive control), or vehicle and exposed to restraint or forced swim stress (FST). CORT 118335 dampened corticosterone responses to both stressors, without a concomitant antidepressant-like effect in the FST. Imipramine decreased corticosterone responses to restraint stress; however, the antidepressant-like effect of imipramine in the FST was independent of circulating glucocorticoids. These findings indicate dissociation between endocrine and behavioral stress responses in the FST. CORT 118335 decreased c-Fos expression only in the CA1 division of the hippocampus. Imipramine decreased c-Fos expression in the basolateral amygdala and CA1 and CA3 divisions of the hippocampus. Overall, the data indicate differential effects of CORT 118335 and imipramine on stress-induced neuronal activity in various brain regions. The data also highlight a complex relationship between neuronal activation in stress and mood regulatory brain regions and the ensuing impact on endocrine and behavioral stress responses.

Age-Dependent Effects of Prenatal Dexamethasone Exposure on Immune Responses in Male Rats.

Prenatal glucocorticoid therapy is indicated in preterm delivery to prevent respiratory distress. This study was designed to evaluate the age-dependent effects of prenatal dexamethasone (DEX) therapy on the immune system using a rat model. Pregnant Sprague-Dawley rats received an intraperitoneal injection of DEX (0.1 mg/kg/day) or saline (VEH) over gestational days 14-20. Male offspring were sacrificed at postnatal day 7 (D7; infant stage), D120 (young adult stage), and D180 (adult stage) for evaluation of leukocyte subsets and isolation of splenocytes. The production of innate and adaptive immune cytokines was assessed from the culture supernatants of splenocytes, stimulated with lipopolysaccharide and concanavalin A, respectively. For innate cytokines, the levels of interferon gamma inducible protein 10 were significantly higher, but those of tumor necrosis factor-α were significantly lower, in the culture medium of splenocytes prepared from the DEX group at D120 than those in the VEH group. For adaptive cytokines, the levels of interleukin-4 (IL-4) were significantly higher at D7 and those of IL-10 were significantly higher at D120 after prenatal exposure to DEX. We also showed that the expression level of IL-4 mRNA was significantly higher in splenocytes prepared from the DEX group at D7, compared with the VEH group. Importantly, the mRNA expression level of T-bet, a key transcription factor for immune cells, was greatly decreased in the spleen of the DEX group at D7, compared with the VEH group. In conclusion, prenatal dexamethasone exposure shows the greater impact on immune responses of their male offspring in early life.

Development of a lipopolysaccharide (LPS)-supplemented adjuvant and its effects on cell-mediated and humoral immune responses in male rats immunized against sperm.

Supplementation with lipopolysaccharide (LPS) from non-pathogenic Escherichia coli was found to enhance the adjuvant effects of a veterinary vaccine adjuvant (ISA 71VG®). Sperm immunization using 71VG as an adjuvant in the immature period induced infertility in 25% of male rats, whereas this increased to 62.5% after immunization with 71VG + LPS or Freund′s complete adjuvant (FCA). Mean testicular weight of non-sterile males in the 71VG + LPS group was significantly lower than that in the 71VG or FCA group. Histological examination of testicular tissue from sterile males demonstrated severe impairment of spermatogenesis due to experimental autoimmune orchitis, a cell-mediated autoimmune condition. The serum anti-sperm titer was elevated in the three sperm-immunized groups relative to male rats treated with adjuvant alone, but the titer was higher in the 71VG + LPS and FCA groups than in the 71VG group. We consider that this LPS-supplemented adjuvant stimulates both humoral and cell-mediated immune responses to an extent comparable to FCA.

Social buffering enhances extinction of conditioned fear responses in male rats

In social species, the phenomenon in which the presence of conspecific animals mitigates stress responses is called social buffering. We previously reported that social buffering in male rats ameliorated behavioral fear responses, as well as hypothalamic-pituitary-adrenal axis activation, elicited by an auditory conditioned stimulus (CS). However, after social buffering, it is not clear whether rats exhibit fear responses when they are re-exposed to the same CS in the absence of another rat. In the present study, we addressed this issue using an experimental model of extinction. High stress levels during extinction training impaired extinction, suggesting that extinction is enhanced when stress levels during extinction training are low. Therefore, we hypothesized that rats that had received social buffering during extinction training would not show fear responses to a CS, even in the absence of another rat, because social buffering had enhanced the extinction of conditioned fear responses. To test this, we subjected male fear-conditioned rats to extinction training either alone or with a non-conditioned male rat. The subjects were then individually re-exposed to the CS in a recall test. When the subjects individually underwent extinction training, no responses were suppressed in the recall test. Conversely, when the subjects received social buffering during extinction training, freezing and Fos expression in the paraventricular nucleus of the hypothalamus and lateral amygdala were suppressed. Additionally, the effects of social buffering were absent when the recall test was conducted in a different context from the extinction training. The present results suggest that social buffering enhances extinction of conditioned fear responses.

Sex-Specific Effect of Endothelin in the Blood Pressure Response to Acute Angiotensin II in Growth-Restricted Rats.

The renal endothelin system contributes to sex differences in blood pressure with males demonstrating greater endothelin type-A receptor-mediated responses relative to females. Intrauterine growth restriction programs hypertension and enhance renal sensitivity to acute angiotensin II in male growth-restricted rats. Endothelin is reported to work synergistically with angiotensin II. Thus, this study tested the hypothesis that endothelin augments the blood pressure response to acute angiotensin II in male growth-restricted rats. Systemic and renal hemodynamics were determined in response to acute angiotensin II (100 mg/kg per minute for 30 minutes) with and without the endothelin type-A receptor antagonist, Atrasentan (ABT-627; 10 ng/kg per minute for 30 minutes), in rats pretreated with enalapril (250 mg/L for 1 week) to normalize the endogenous renin-angiotensin system. Endothelin type-A receptor blockade reduced angiotensin II-mediated increases in blood pressure in male control and male growth-restricted rats. Endothelin type-A receptor blockade also abolished hyper-responsiveness to acute angiotensin II in male growth-restricted rats. Yet, blood pressure remained significantly elevated above baseline after endothelin type-A receptor blockade, suggesting that factors in addition to endothelin contribute to the basic angiotensin II-induced pressor response in male rats. We also determined sex-specific effects of endothelin on acute angiotensin II-mediated hemodynamic responses. Endothelin type-A receptor blockade did not reduce acute angiotensin II-mediated increases in blood pressure in female control or growth-restricted rats, intact or ovariectomized. Thus, these data suggest that endothelin type-A receptor blockade contributes to hypersensitivity to acute angiotensin II in male growth-restricted rats and further supports the sex-specific effect of endothelin on blood pressure.

17β-Estradiol Enhances ASIC Activity in Primary Sensory Neurons to Produce Sex Difference in Acidosis-Induced Nociception

Sex differences have been reported in a number of pain conditions. Women are more sensitive to most types of painful stimuli than men, and estrogen plays a key role in the sex differences in pain perception. However, it is unclear whether there is a sex difference in acidosis-evoked pain. We report here that both male and female rats exhibit nociceptive behaviors in response to acetic acid, with females being more sensitive than males. Local application of exogenous 17β-estradiol (E2) exacerbated acidosis-evoked nociceptive response in male rats. E2 and estrogen receptor (ER)-α agonist 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole, but not ERβ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile, replacement also reversed attenuation of the acetic acid-induced nociceptive response in ovariectomized females. Moreover, E2 can exert a rapid potentiating effect on the functional activity of acid-sensing ion channels (ASICs), which mediated the acidosis-induced events. E2 dose dependently increased the amplitude of ASIC currents with a 42.8 ± 1.6 nM of EC50. E2 shifted the concentration-response curve for proton upward with a 50.1% ± 6.2% increase of the maximal current response to proton. E2 potentiated ASIC currents via an ERα and ERK1/2 signaling pathway. E2 also altered acidosis-evoked membrane excitability of dorsal root ganglia neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acidic stimuli. E2 potentiation of the functional activity of ASICs revealed a peripheral mechanism underlying this sex difference in acetic acid-induced nociception.

Adrenal response of male rats exposed to prenatal stress and early postnatal stimulation

Stress in pregnant rats caused by chronic immobilization alters the pattern of secretion of corticosterone and modifies the hypothalamic-pituitary-adrenal axis (HPA) of the fetus. Early postnatal handling, however, may reverse the effects of increased secretion of corticosterone. We investigated the effects of prenatal stress and postnatal handling on the activity of the HPA axis of male offspring of stressed female rats. Male 90-day-old rats from four groups were investigated: prenatally stressed animals without postnatal handling, prenatally stressed animals with postnatal handling, unstressed control animals with postnatal handling, and unstressed control animals without postnatal handling. After sacrifice, the adrenal glands were weighed to determine the adrenal-somatic index. Apoptosis was evaluated by TUNEL assay and active caspase-3 expression. We found that the adrenal gland cortex:medulla ratio increased in animals with prenatal stress and that eventually the stress caused apoptosis. Handling newborns to simulate maternal activity ameliorated some of the negative effects of prenatal stress.

Effects of dietary Thymus vulgaris extract alone or with atorvastatin on the liver, kidney, heart, and brain histopathological features in diabetic and hyperlipidemic male rats

Thymus vulgaris (thyme) is commonly used in folk medicine for several therapeutic purposes. The aim of the present study was to evaluate the histopathological changes in the four vital organs, liver, kidney, heart, and brain, of diabetic and hyperlipidemic male rats after consumption of different doses of hydroalcoholic extract of thyme alone or in 11 combinations with atorvastatin. In a double-blind animal-based controlled randomized clinical trial, 90 male rats were randomly allocated into nine equal independent groups, according to consumption of atorvastatine and/or T. vulgaris extract, and the histopathological changes of vital organs of diabetic and hyperlipidemic male rats in response to T. vulgaris extract were evaluated. Our results indicated that in diabetes mellitus and hyperlipidemia, the liver and brain were observed to have more histopathological lesions than the kidney and heart. Also, after using atorvastatin, the frequency of brain histopathological lesions was decreased. In treatment groups, by increasing the dose of thyme extract, the hepatic histopathological lesions were disappeared and a decline in brain histopathological lesions was seen. It is found that atorvastatine can decrease the histopathological lesions especially in liver, if used alone or in combination with T. vulgaris extract.

Effects of lesion of posterior part of cerebellar vermis and fastigial nuclei on some immune responses in male rats

Considering the autonomic function of cerebellum, it is a potential neural area for immunomodulation. Though the role of fastigial nucleus (FN) and vestibulocerebellum on immunomodulation has been investigated, the results are contradictory. In the present study the role of posterior cerbellar vermis (PV) and FN on some immunological parameters such as TC and DC of WBC, leukocyte adhesive inhibition index (LAI) of splenic mononuclear cell (MNC) and phagocytic activity of peripheral WBC by fluorescence activated cell sorter (FACS) were investigated after two and three weeks lesions of PV (lobules VII, IX and X) and FN by aspiration technique in male rats. The TC of WBC was decreased after two weeks of PV+FN lesioned rats compared to that of sham lesion and control rats. The percentage neutrophil and eoisinophil counts were increased and the lymphocyte count was decreased after two weeks of PV+ FN lesioned rats compared to that of sham operated and control rats. The phagocytic activity of blood WBC and LAI of splenic MNC were increased after two weeks of PV+FN lesioned rats compared to that of sham lesioned and control rats. After three weeks of PV+FN lesioned these immunological parameters were regain to the normal level. The results indicate that the combined lesion of PV and FN induced enhanced immune responses but this effect is transitory.

Expression of nerve growth factor in the prostate of male rats in response to chronic stress and sympathetic denervation.

Nerve growth factor (NGF) has been found in the normal prostate of the Wistar rat and is regarded as an important prostatic mitogen. We have previously shown that chronic stress induced epithelial hyperplasia while sympathetic denervation caused atrophy in the male Wistar rat prostate. NGF may have been a contributing mechanism to the hyperplasia and atrophy response that was observed. The aim of the present study was to investigate the expression of NGF in the prostate of the male rat in response to chronic stress and denervation. Two weeks of restraint water-immersion stress were used to induce a chronic stress model in Wistar rats. Denervation of the peripheral sympathetic nerve was induced by 6-hydroxydopamine. The expression levels of NGF in the dissected prostate lobes were examined by immunohistochemistry. After 14 days of stress, proliferation of the epithelium in the ventral lobes was observed, whereas the dorsolateral lobes were almost unaffected. NGF immunoreactive protein was localized to the columnar secretory epithelium lines of the prostate tissue. Stress and denervation led to an increase in NGF expression in the ventral lobes. In conclusion, NGF was involved in the hyperplasia and atrophy in the prostate of the male rat in response to chronic stress and sympathetic denervation, and thus may be a contributing factor in the pathophysiology of the prostate.

Central vasopressin V1A receptor blockade alters patterns of cellular activation and prevents glucocorticoid habituation to repeated restraint stress exposure

Our previous experiments implicated a role for the arginine vasopressin (AVP) V1A receptor subtype in mediating the normal decline (habituation) of hypothalamic-pituitary-adrenal (HPA) axis responses to repeated restraint exposure. To explore pathways mediating the endogenous effects of central AVP on stress HPA axis habituation, here we compared cellular (Fos) and hormone responses in male rats receiving chronic icv infusion of vehicle or a V1A receptor antagonist that began 7 d before stress testing, continued through the duration of acute and repeat restraint exposure. As a group, rats with V1A antagonism displayed a modest reduction in ACTH habituation, whereas the decline in corticosterone was completely prevented. V1A antagonized rats also showed reduced evidence of habituated Fos responses in the paraventricular nucleus of the hypothalamus, medial amygdala, and within the anterior division of the bed nucleus of the stria terminalis. Based on these cellular and neuroendocrine responses, we then examined whether repeated restraint is reflected by changes in V1A receptor binding. Relative to stress naïve animals, repeatedly exposed rats showed lower levels of V1A binding in the dentate gyrus of the hippocampus, thalamus and central amygdala, but higher levels in the septum and anterior BST. Taken together, these findings suggest that AVP may act within multiple targets to regulate the normal decline in stress-induced drive to the HPA axis, and that this may involve the net of V1A receptor stimulatory and inhibitory influences on neuroendocrine habituation.

Changes in the sexual behavior and testosterone levels of male rats in response to daily interactions with estrus females

Male rat sexual behavior has been intensively studied over the past 100years, but few studies have examined how sexual behavior changes over the course of several days of interactions. In this experiment, adult male rats in the experimental group (n=12) were given daily access to estrus females for 30min per day for 15 consecutive days while control males (n=11) did not interact with females. Ovariectomized females were induced into estrus with hormonal injections, and males interacted with a different female each day. The amount of sexual activity (mounts, intromissions, and ejaculations) was found to cycle with a period of approximately 4days in most male rats. Additionally, blood was collected every other day following sexual interactions to assess serum testosterone levels. Testosterone was found to peak on the first day of interaction and then fell back to near the level of control rats that did not interact with females. Following the initial peak, testosterone concentrations fluctuated less in males exposed to females than in controls. Sexual activity was not found to predict testosterone concentration. We conclude that when male rats have daily sexual interactions, sexual behavior tends to show cyclic changes and testosterone is significantly elevated only on the first day of interactions.

Sexual odor discrimination and physiological profiles in adult male rats after a neonatal, short term, reversible nasal obstruction.

The present study was designed to examine behavioral responses (interpreted as preferences) to olfactory cues (nest bedding odor and odors of estrous and anestrus females) in adult male rats after they had a short term reversible, bilateral, nasal obstruction (RbNO) as developing rat pups. These results were compared to behavior of control (untreated) and sham operated male littermates. Behavioral tests and physiological parameters were analyzed 90 days after recovery of nasal breathing. Experiments investigated the time spent in arms or the center of a maze of male rats in response to odors from the nest bedding or from adult females. There were no differences in responses between untreated, sham and RbNO adult male rats to fresh and nest bedding odors. RbNO males spent more time in the center of the maze when given a choice of estrus or anestrus female odors, or bedding odors from untreated or sham operated female rats. In contrast untreated and sham male rats preferred the odors of estrous females and of untreated or sham females. Plasma corticosterone levels in the males increased during the behavioral tests. Plasma testosterone levels were significantly lower in RbNO males compared to untreated males and did not increase during the behavioral tests compared to sham operated males. Males from all groups had similar preferences for the odor of bedding from adult RbNO females. Plasma levels of cholesterol and triglycerides were increased in RbNO adults. In conclusion, short term nasal obstruction in males while juvenile has long term consequences on hormones and behavioral preferences, thus potential partner selection when adult.

A familiar conspecific is more effective than an unfamiliar conspecific for social buffering of conditioned fear responses in male rats

In social animals, the presence of an affiliative conspecific alleviates acute stress responses, and this is called social buffering. We previously reported in male rats that the presence of a conspecific mitigates conditioned fear responses to auditory conditioned stimulus paired with foot shocks. Subsequent studies revealed that we could observe this social buffering when rats were tested in a box odorized by a conspecific. Because we previously used an unfamiliar conspecific, the effects of familiarity with a conspecific on the intensity of social buffering remain unclear. Here, we examine this question by preparing a familiar conspecific that had been housed with a subject for 3 weeks in the same cage. We exposed fear-conditioned subjects to a conditioned stimulus in either a clean control box or a box odorized beforehand by either an unfamiliar or a familiar conspecific. When the subjects were tested in the control box, they showed freezing and Fos expression in the paraventricular nucleus. These responses were suppressed when we placed rats in the box odorized by a conspecific. However, the suppression was greater when the box was odorized by a familiar conspecific rather than by an unfamiliar conspecific. Fos expression in the lateral amygdala was also suppressed in the same manner. These results suggest that a familiar conspecific is more effective for social buffering of conditioned fear responses.