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Adult Sprague-Dawley rats were exposed to a single session of 100 inescapable tail shocks (IS). Bromodeoxyuridine (BrdU) was administered 1 h, 2 days or 7 days later and hippocampal cell proliferation (CP) was assessed after a 2-h survival period. Measures of plasma corticosterone (CORT) levels were also obtained. Despite a large increase in CORT immediately following IS, no associated change in CP was observed. In fact, the only significant change in CP was seen 7 days after IS, at a time when CORT was unchanged from control levels. These data raise questions about the general nature of the relationship between CORT and CP. They also suggest that, under some conditions, changes in hippocampal CP may emerge only after an "incubation period".

Compared with the use of classic receptor ligands, antisense oligonucleotides (ASO) targeted at specific central nervous system receptors are an effective alternative in experiments designed to examine the behavioral role of such systems.The nociception/orphaninFQ (N/OFQ) system has been implicated in mediating endocrine function, feeding, stress, pain, anxiety, and the rewarding effects of drugs of abuse. The objective of the current study was to examine whether long-term ASO-induced downregulation of N/OFQ's receptor (NOP) produced changes in endocrine, anxiety, nociception and ethanol's (EtOH's) locomotor activating properties.Male Long Evans rats were implanted with osmotic mini-pumps containing ASO for the NOP receptor. ASO was chronically infused for 26 days and, during this time, multiple behavioral and physiological measurements were conducted.ASO infusion significantly reduced expression of the NOP receptor in brain, confirmed by significant reductions of OFQ-stimulated [(35)S]-GTPgammaS binding in the paraventricular nucleus, prefrontal cortex, and septum. Behavioral changes were observed in ASO-treated animals including higher body temperature, increased water intake, decreased corticosterone (CORT) levels, decreased grooming in the open field, increased tail-flick latency, shorter durations on the open arms of the elevated plus maze, and heightened locomotor activity following EtOH.These behavioral, physiological and endocrine changes are relatively consistent with previous findings with agonists and antagonists for the NOP receptor and, taken together, suggest that ASO-induced downregulation of the NOP receptor is an effective method for studying the N/OFQ system.

Social stressors, like other stressors, are powerful activators of the sympathoadrenomedullary system. Differential housing (single vs. group) and social defeat of rats is known to alter the activity of catecholamine-synthesizing enzymes in the medulla. The present studies examined the effect of 70 days of triad (3 rats per large cage) and individual housing of male rats on adrenal mRNA levels of tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) and on TH protein levels. Behavioral ratings carried out at the triad formation indicated that dominant rats exhibited mostly offensive aggressive behaviors. By contrast, subordinate rats expressed primarily defensive behaviors, while the subdominant rats displayed intermediate levels of these behaviors. Overall, compared with single housing, triad housing resulted in lower gene expression for TH, DBH and PNMT and lower TH protein in the adrenals. Within triads, gene expression for these enzymes and TH protein concentration were higher in subordinate compared with dominant and subdominant rats. The dominant rats tended to have the lowest gene expression of these enzymes. These data indicate that in rodents, individual housing and a subject’s social rank have a differential impact on the regulation of catecholamine biosynthesis already during the process of gene expression of catecholamine biosynthetic enzymes in the adrenals.

Pheromones are volatile chemical cues that in rodents originate in large part from the preputial glands and influence various behavioral and physiological processes. We have examined the effect of psychosocial stress on volatile compound composition of preputial glands of male rats. Rats were housed three per cage or singly for 70 days. Dominants had heavier preputials compared to subdominant and subordinate rats. Capillary gas chromatographic mass spectrometry identified 55 volatile preputial compounds: 17 did not differ between groups, while 26 compounds were higher in single-housed compared to triad-housed rats. Six compounds were higher in dominant, while another six were higher in both dominant and single-housed rats. We conclude that both housing condition and rank status have significant differential effects on the preputial volatile compounds.

In rodents the preputial glands are one of the major sources of pheromones. These volatile chemosignaling compounds are known to elicit specific behavioral and physiological effects in their conspecifics. While social stress can alter both the behavior and hormonal status of rodents, little is known about its influence on the volatile constituents of the preputial glands. We have examined the composition of volatile compounds in the preputial glands of gonadally intact male rats housed for 70 days in either unisex triads (three/cage) or singly. The rank status of triad-housed rats was based on quantitative behavioral assessments taken during the initial 30 min of triad housing. Dominant rats had heavier preputial glands compared to subdominant and subordinate rats. Capillary gas chromatography-mass spectrometry identified 56 volatile preputial compounds, of these 17 did not differ between groups while 26 compounds were significantly higher in the single-housed compared to the triad-housed rats. Six additional volatile compounds were higher in the dominant compared to the other 3 groups, while another six compounds were higher in both the dominant and single-housed rats compared to the subdominant and subordinate rats. It can be concluded that both housing condition and social rank status have significant but different effects on the composition of volatile compounds found in preputial glands of male rats. The physiological and behavioral significance of these changes in preputial gland volatile compound composition in rats remain to be investigated.

Psychosocial stress, including social rank status, has been shown to alter spontaneously occurring behaviors in rodents as well as the behavioral effects of drugs of abuse. In this study, rats were repeatedly evaluated in a modified open field following: their initial exposure, and after intraperitoneal injections of saline and 0.75 g/kg ethanol (EtOH). All subjects were first tested while under single housing conditions, then again following 35 days of differential housing (singly or 3 rats/cage) with social status determined by scoring agonistic behavior at triad formation. The data suggest that (1) future subordinate rats differed with respect to specific aspects of behavior displayed in a 'novel' open field arena, (2) future subordinate rats were more emotional since they showed greater "anxiety-like" behavior and less exploratory behavior, (3) subordinate rats were more impaired by the saline injection stress, (4) subordinate rats were more sensitive to the depressant effects of EtOH, (5) grooming behavior did not show habituation, in contrast to the other behaviors, but showed sensitization on the second test. Overall, subordinate rats may have differed from their cage mates in innate anxiety, and this may underlie their distinct response to both stressors and EtOH. Furthermore, while EtOH had mostly stimulant effects in naive rats, psychosocial stress and/or repeated testing resulted in enhancement of EtOH's depressant effects.

Most alcohol researchers do not address the effects of intoxication on the sympatho-adrenomedullary system response to stressful situations. We previously determined that rats consuming nearly 9 g ethanol (EtOH) per kg body weight per day in liquid diet form for 1 week increased adrenal gene expression of enzymes for catecholamine synthesis that was further elevated by acute IMMO. We hypothesized that the response to chronic mild stressors would also be altered after consumption of lower concentrations of EtOH in drinking water. Two experiments were conducted: 10% w/v for 4 weeks or 6% w/v for 7 weeks +/- wire mesh restraint (WMR). These were compared with ad libitum (adlib) and pair-fed control rats. Adrenal gene expression of catecholamine synthesizing enzymes was assayed. Tyrosine hydroxylase gene expression was elevated 80% to 90% by alcohol consumption in both experiments (P0.001) compared with adlib control rats. Dopamine betab-hydroxylase and phenylethanolamine-N-methyl transferase gene expressions were unaffected by 10% alcohol (P0.05) but were increased by 6% alcohol (P0.01). WMR decreased already elevated gene expression of all three enzymes. Pair feeding to 6% EtOH drinkers also increased gene expression for the three enzymes but was decreased by WMR, although not to levels of adlib rats. Increased gene expression for adrenal synthesis of catecholamines in response to repeated alcohol consumption increases the likelihood that the subject can respond physiologically to acute or chronic stress. This may have life-saving consequences in humans and in animals known to consume fermented materials and may contribute to increased aggressive behavior.