Single-housed Rats Research Articles

Fast-acting antidepressant-like effects of ketamine in aged male rats

BackgroundThe aging process causes anatomical and physiological changes that predispose to the development of late-life depression while reduces the efficacy of classical antidepressants. Novel fast-acting antidepressants such as ketamine might be good candidates to be explored in the context of aging, especially given the lack of previous research on its efficacy for this age period. Thus, the aim of the present study was to characterize ketamine’s effects in older rats.MethodsThe fast-acting (30 min) and repeated (7 days) antidepressant-like effects of ketamine (5 mg/kg, ip) were evaluated in 14-month-old single-housed rats through the forced-swim and novelty-suppressed feeding tests. In parallel, the modulation of neurotrophic-related proteins (i.e., mBDNF, mTOR, GSK3) was assessed in brain regions affected by the aging process, prefrontal cortex and hippocampus, as well as possible changes in hippocampal cell proliferation.ResultsAcute ketamine induced a fast-acting antidepressant-like response in male aged rats, as observed by a reduced immobility in the forced-swim test, in parallel with a region-specific increase in mBDNF protein content in prefrontal cortex. However, repeated ketamine failed to induce antidepressant-like efficacy, but decreased mBDNF protein content in prefrontal cortex. The rate of hippocampal cell proliferation and/or other markers evaluated was not modulated by either paradigm of ketamine.ConclusionsThese results complement prior data supporting a fast-acting antidepressant-like effect of ketamine in rats, to further extend its efficacy to older ages. Future studies are needed to further clarify the lack of response after the repeated treatment as well as its potential adverse effects in aging.

Pair housing does not alter incubation of craving, extinction, and reinstatement after heroin self-administration in female and male rats.

Evidence suggests that single housing in rats acts as a chronic stressor, raising the possibilities that it contributes to measures of heroin craving and that pair housing ameliorates such measures. This study aimed to determine whether pair housing after heroin self-administration reduces the incubation of craving, extinction, and reinstatement of heroin seeking. Single-housed female and male Sprague-Dawley rats underwent daily 6-hr heroin self-administration, wherein active lever presses produced a heroin infusion paired with light/tone cues. One day after self-administration, rats underwent a baseline cued-seeking test wherein active lever presses only produced light/tone cues. Immediately following this cued-seeking test, rats were either pair-housed with weight- and sex-matched naïve rat or remained single-housed for the rest of the study. For 14 days, rats remained in their homecages, after which they underwent a cued-seeking test to assess the incubation of craving compared to their baseline test. Rats then underwent extinction sessions followed by cue-induced and heroin-primed reinstatements. The findings reveal that pair-housed rats did not differ from single-housed rats in terms of the incubation of craving, extinction, or reinstatement of heroin seeking. Additionally, the results did not reveal any evidence of sex-based differences in the study. The present work indicates that pair housing during the forced abstinence period does not alter measures of heroin craving/seeking. These findings suggest that the chronic stress of single housing specifically during forced abstinence does not contribute to the degree of such measures. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Operant social seeking to a novel peer after social isolation is associated with activation of nucleus accumbens shell in rats.

Deprivation of social interaction promotes social reward seeking in rodents, assessed primarily by the conditioned place preference procedure. Here, we used an operant social procedure in rats and examined the effect of the housing condition (pair-housing vs. single-housing) during or after social self-administration on social reward seeking. We first trained paired-housed or single-housed rats to gain access to an age- and sex-matched novel peer. On post-training day 1 (PTD1), we tested both groups for social seeking without the presence of the novel peer. Next, we divided each group into pair-housing or single-housing conditions and tested all four groups (pair-pair, pair-single, single-pair, and single-single) for social seeking on post-training day 12 (PTD12). Finally, we analyzed Fos expression in the striatum associated with social seeking on PTD12. Single-housed rats earned more social rewards during social self-administration than pair-housed rats. Social isolation during social self-administration also promoted social seeking on PTD1 and PTD12, regardless of their housing conditions after social self-administration training. Additionally, in pair-housed rats, social isolation during the post-training period led to a time-dependent increase of social seeking on PTD12 compared with PTD1. Finally, the Fos analyses revealed an increase of Fos expression in NAc shell of single-single rats after social seeking test on PTD12 compared with pair-pair rats. Our data suggest that social isolation promotes operant social self-administration and social seeking. In addition, neuronal activation of NAc shell is associated with social seeking after social isolation.

The Influence of Social Isolation on Social Orientation, Sociability, Social Novelty Preference, and Hippocampal Parvalbumin-Expressing Interneurons in Peripubertal Rats - Understanding the Importance of Meeting Social Needs in Adolescence.

The fulfillment of belonging needs underlies a variety of behaviors. In order to understand how social needs unmet during maturation shape everyday life, we examined social motivation and cognition in peripubertal rats, as a rodent model of adolescence, subjected to social isolation (SI) during early and early-to-mid adolescence. The behavioral correlates of social orientation (social space preference), sociability (preference for social over non-social novelty), and social novelty preference (SNP) were examined in group-housed (GH) and single-housed (SH) rats in a 3-chamber test. The response to social odors was examined to gain insights into the developmental role of social odors in motivated social behavior. Differentiation between appetitive (number of visits/approaches) and consummatory (exploratory time) aspects of motivated social behavior was done to determine which facet of social motivation characterizes maturation when social needs are met and which aspect dominates when social needs are unsatisfied. The SI-sensitive parvalbumin-expressing interneurons (PVI) in the hippocampus were examined using immunohistochemistry. The main findings are the following: (1) in GH rats, the preference for social space is not evident regardless of animals’ age, while sociability becomes apparent in mid-adolescence strictly through consummatory behavior, along with complete SNP (appetitive, consummatory); (2) SH promotes staying in a social chamber/space regardless of animals’ age and produces an appetitive preference for it only in early-adolescent animals; (3) SH promotes sociability (appetitive, consummatory) regardless of the animals’ age and prevents the SNP; (4) the preference for a social odor is displayed in all the groups through consummatory behavior, while appetitive behavior is evident only in SH rats; (5) the response to social odors does not commensurate directly to the response to conspecifics; (6) SH does not influence PVI in the hippocampus, except in the case of early-adolescence when a transient decrease in the dentate gyrus is observed. These results accentuate the developmental complexity of social motivation and cognition, and the power of SI in adolescence to infringe social maturation at different functional levels, promoting appetitive behavior toward peers overall but harming the interest for social novelty. The findings emphasize the importance of the fulfillment of basic social needs in the navigation through the social world.

Social isolation of adolescent male rats increases anxiety and K+ -induced dopamine release in the nucleus accumbens: Role of CRF-R1.

Early life adversity can disrupt development leading to emotional and cognitive disorders. This study investigated the effects of social isolation after weaning on anxiety, body weight and locomotion, and on extracellular dopamine (DA) and glutamate (GLU) in the nucleus accumbens (NAc) and their modulation by corticotropin releasing factor receptor 1. On the day of weaning, male rats were housed singly or in groups for 10 consecutive days. Anxiety-like behaviors were assessed by an elevated plus maze (EPM) and an open field test (OF). Neurotransmitter levels were measured by in vivo microdialysis. Single-housed rats spent less time, and entered more, into the closed arms of an EPM than group-housed rats. They also spent less time in the center of an OF, weighed more and showed greater locomotion. In the NAc, no differences in CRF, or in basal extracellular DA or GLU between groups, were observed. A depolarizing stimulus increased DA release in both groups but to higher levels in isolated rats, whereas GLU increased only in single-housed rats. Blocking CRF-R1 receptors with CP-154,526 decreased DA release in single-housed but not in group-housed rats. The corticotropin releasing factor receptor type 1 receptor antagonist also decreased GLU in group-housed animals. These results show that isolating adolescent rats increases anxiety, body weight and ambulation, as well as the sensitivity of dopaminergic neurons to a depolarizing stimulus. This study provides further evidence of the detrimental effects of social isolation during early development and indicates that dysregulation of the CRF system in the NAc may contribute to the pathologies observed.

Incubation of Oxycodone Craving Following Adult-Onset and Adolescent-Onset Oxycodone Self-Administration in Male Rats.

Relapse is a major obstacle to curb the ongoing epidemic of prescription opioid abuse. We and others previously demonstrated that oxycodone seeking in adult rats progressively increases after abstinence from oxycodone self-administration (incubation of oxycodone craving). In humans, the onset of oxycodone use in adolescents may increase individuals’ vulnerability to later opioid addiction. However, little is known about incubation of oxycodone craving after adolescent-onset oxycodone self-administration in rats. In the first study, we trained single-housed adolescent (postnatal day 35 at start) and adult (postnatal day 77 at start) male Sprague–Dawley rats to self-administer oxycodone (0.1 mg/kg/infusion, 6 h/day for 10 days) and then tested oxycodone relapse on both abstinence day 1 and day 15. Given that social experience is critical for neurobehavioral development in adolescents, we performed the second study using group-housed adolescent and adult rats. In both studies, we observed no age differences in oxycodone self-administration and incubated oxycodone seeking on abstinence day 15. However, on abstinence day 1, we observed decreased oxycodone seeking in adolescents compared with adults. This pattern of data led to elevated incubation slopes in adolescent rats compared with adult rats. Finally, group-housed rats exhibited attenuated oxycodone seeking compared with single-housed rats on abstinence day 15, but not on day 1. Taken together, these data suggest that adolescents may be resistant to oxycodone relapse during early abstinence, but this resistance dissipates quickly during the transition between adolescent and young adulthood. In addition, group-housing plays a protective role against incubated oxycodone craving.

Prolonged Social Isolation, Started Early in Life, Impairs Cognitive Abilities in Rats Depending on Sex.

Background: The chronic stress of social isolation is a valid predictor of cognitive pathology. This study aimed to compare the effects of long-term social isolation on female versus male Wistar rats’ learning and memory. We hypothesized that prolonged social isolation stress, which starts early in life, would affect learning in a sex-dependent manner. Methods: Social isolation started at the edge of early to mid-adolescence and lasted 9 months. The rat’s cognitive abilities were assessed by habituation and reactivity to novelty in the open field (OF) test, spatial memory in the Morris water maze (MWM), and the conditioned passive avoidance (PA) reflex. Basal serum corticosterone levels were assessed using an enzyme-linked immunosorbent assay. Results: Regardless of the housing conditions, females habituated to the OF under low illumination slower than males. Under bright light, the single-housed rats showed hyporeactivity to novelty. In the MWM, all the rats learned to locate the platform; however, on the first training day, the single-housed females’ speed was lower relative to other groups. Four months later, in the post-reminder probe trial, the single-housed rats reached the area around the platform site later, and only males, regardless of housing conditions, preferred the target quadrant. Single-housed rats, irrespective of sex, showed a PA deficit. There was a more pronounced conditioned fear in the single-housed males than in females. In both male and female rats, basal corticosterone levels in rat blood serum after 9 months of social isolation did not differ from that in the group-housed rats of the corresponding sex. Meanwhile, females’ basal corticosterone level was higher than in males, regardless of the housing conditions. The relative weight of the adrenal glands was increased only in single-housed females. Conclusions: Under long-term social isolation, started early in life, single-housed females compared with males showed more pronounced cognitive impairments in the MWM and PA paradigm, findings that specify their greater vulnerability to the stress of prolonged social isolation.

Role of adolescent-formed, context-drug-associations on reinstatement of drug-seeking behavior in rats.

Drug use during adolescence results in a lifelong risk to develop substance-use disorders. Adolescent rats are less reactive to cocaine-associated cues compared with adults; however, the contribution of adolescent-formed, context-drug-associations to elicit relapse-like behavior is underexplored. Although it is known that social isolation can impact drug-seeking behavior, the effects of housing conditions on context-induced, cocaine-seeking during adolescence vs adulthood are unknown. The present study compared the effect of adolescent vs adult-formed context-drug associations under different housing conditions (pair vs single) on cocaine-seeking behavior during adolescence or adulthood. This objective was accomplished using operant cocaine self-administration (Coc-SA) under a standard, non-abbreviated (Non-ABRV) or modified abbreviated (ABRV) paradigm. In experiment 1, adolescent and adult rats received Non-ABRV Coc-SA in a distinct context (2h, 1×/day, 10days), and extinction training (EXT) in a second context (1h, 1×/day, 8days) with reinstatement test (TEST) during adulthood in the cocaine-paired context. In experiments 2 and 3, rats received all behavioral phases during adolescence or adulthood: ABRV Coc-SA (2h, 2×/day, 5days), EXT (1h, 4×/day, 2days) with TEST in a cocaine-paired or novel, unpaired context. All experiments included pair and single-housing conditions. Age at cocaine exposure did not influence behavior in Non-ABRV or ABRV paradigms. Under Non-ABRV conditions, adolescent and adult single-housed rats had higher seeking behavior than pair housed. These data suggest that social isolation influences context-induced, cocaine-seeking regardless of age at drug exposure and provides a condensed, ABRV paradigm to investigate context-induced, cocaine-seeking behavior during adolescence.

Predator odor stress blunts alcohol conditioned aversion

Alcohol use disorder is highly co-morbid with traumatic stress disorders in humans, and dually diagnosed individuals cite negative affective symptoms as a primary reason for drinking alcohol. Therefore, it is reasonable to hypothesize that traumatic stress history increases the rewarding properties and/or blunts the aversive properties of alcohol. We used a place conditioning procedure to test the rewarding/aversive properties of alcohol in adult male Wistar rats with or without a traumatic stress (i.e., predator odor exposure) history, and with or without an alcohol drinking history. Because extended amygdala regions have documented roles in stress, reward, and stress-induced changes in reward, we also tested the effect of acute alcohol on CREB phosphorylation (pCREB) and striatal-enriched protein tyrosine phosphatase (STEP) expression in central amygdala (CeA) and bed nucleus of stria terminalis (BNST). Our results show that a moderate alcohol dose (1.0 g/kg) produces conditioned place aversion (CPA) that is blunted by stress history but is not affected by alcohol drinking history, and this effect differed in pair-housed versus single-housed rats. Stress history reduced pCREB expression in BNST of rats with and without an alcohol drinking history. Finally, acute alcohol effects on pCREB and STEP expression in CeA were positively associated with preference for the alcohol-paired chamber. These data suggest that stress history reduces the aversive properties of moderate alcohol doses, and that alcohol aversion is associated with acute alcohol effects on pCREB and STEP expression in the extended amygdala.

Activation patterns of vasopressinergic and oxytocinergic brain regions following social play exposure in juvenile male and female rats.

Social play is a highly rewarding and motivated behavior predominately displayed by juveniles and expressed by nearly all mammalian species. Prior work suggested that the vasopressin (AVP) and oxytocin (OT) systems can regulate the expression of social play in sex-specific ways. Here we investigated whether there are sex differences in the recruitment of vasopressinergic and oxytocinergic brain regions following social play exposure in juvenile rats. Single-housed rats were allowed to play, in their home cage, with an age- and sex-matched unfamiliar conspecific for 10 min, or received similar handling but no partner. Double-labeled fluorescent immunohistochemistry for Fos and either AVP or OT was completed in adjacent series of tissue to determine recruitment of AVP- and OT-immunoreactive neurons in response to social play. Exposure to social play did not increase recruitment of AVP or OT neurons in the supraoptic (SO) or paraventricular (PVH) hypothalamic nuclei of either sex compared to the no-play control condition. Interestingly, there was a robust sex difference in SO recruitment, irrespective of social play condition, with males exhibiting twice the recruitment of SO-AVP and SO-OT neurons compared to females. Lastly, exposure to social play increased recruitment of the posterior bed nuclei of the stria terminalis (pBST) and the posterodorsal medial amygdalar nucleus (MEApd) compared to the no-play control condition, and this effect was most pronounced in females. Our findings revealed sex differences in the recruitment of brain regions (i) independent of play condition (i.e., SO) possibly representing a sex difference in the baseline levels of AVP and OT signaling required for typical functioning and (ii) specific to play condition (i.e., pBST, MEApd). In sum, this study provides further evidence that the neural substrates underlying social play behavior are sex-specific. This article is protected by copyright. All rights reserved.

Pubertal pair-housing facilitates adult sexual behavior in male rats.

This study examined the effects of pubertal testosterone (T) and social housing manipulations on male sexual behavior in adult rats. Prepubertal rats were castrated at 21 days of age (P21) and implanted with either blank or T-releasing pellets. At the onset of puberty, P28, half the rats in each treatment group were either single- or pair-housed with a male of the same hormone condition through P56, at which time pellets were removed and all rats were single-housed. In adulthood (P84), all rats received T replacement and were tested for sexual behavior. Rats pair-housed during adolescence showed more sexual behavior and greater improvement of sexual performance over repeated tests than single-housed rats, regardless of pubertal T status. Pubertal T, however, did facilitate the frequency of anogenital investigation. Thus, in male rats, social interactions during adolescence are more important than exposure to pubertal T in enhancing adult sexual behavior.

The assessment of single-housed vs. pair-housed rats on the Irwin test

The assessment of single-housed vs. pair-housed rats on the Irwin test

Brief Exposure to Novel or Enriched Environments Reduces Sucrose Cue-Reactivity and Consumption in Rats after 1 or 30 Days of Forced Abstinence from Self-Administration

Environmental enrichment (EE) reduces drug and sucrose cue-reactivity in rats. In a previous study we reported that 1 month of EE (large cage, toys, and social cohorts) significantly reduced sucrose cue-reactivity. In the present study, we examined whether overnight (22 h) EE would be as effective. We also examined whether social enrichment (SE), enrichment alone (SoloEE), or exposure to an alternative environment (AEnv) might account for the EE effect. Rats self-administered 10% sucrose (.2 mL/delivery) in 10 daily 2-h sessions. Sucrose delivery was accompanied by a tone+light cue. Rats were then exposed to enrichment or alternative environment conditions overnight (acute) or for 29 days (chronic). Sucrose cue-reactivity was measured after this period of forced abstinence in a session identical to training, but no sucrose was delivered with the cue. All acute conditions markedly reduced sucrose cue-reactivity after 1 day of forced abstinence compared to single-housed rats in standard vivarium housing (CON). Sucrose consumption was also significantly reduced in all groups but SoloEE in a next-day test. All acute conditions but SE significantly reduced sucrose cue-reactivity when administered just prior to Day 30 of forced abstinence; all reduced sucrose consumption in a next-day test. All chronic conditions except for SE and AEnv significantly reduced sucrose cue-reactivity on the Day 30 test and sucrose consumption in a next day test. For both acute and chronic comparisons, EE manipulations were the most effective at reducing sucrose cue-reactivity and consumption. SoloEE and EE were equally effective at reducing sucrose cue-reactivity and similarly effective at reducing sucrose consumption. This indicates that social interaction is not a necessary condition for reducing sucrose-motivated behaviors. These results may be useful in the development of anti-relapse strategies for drug and food addictions.

Psychoactive ‘Bath Salts’: Compounds, Mechanisms, and Toxicities

Recently, there has been an alarming increase in the abuse of so-called ‘bath salts' products sold on the internet and in retail shops. These products have no legitimate use as bath additives, rather they are purchased as legal alternatives to illicit drugs like cocaine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) (Prosser and Nelson, 2012; Spiller et al, 2011). Bath salts powders are self-administered by insufflation (ie, snorted), taken orally or injected intravenously (i.v.). Recreational doses of bath salts enhance mood and increase alertness, whereas higher doses can lead to dangerous neurological and cardiovascular complications. The psychoactive constituents in bath salts have been identified as synthetic derivatives of cathinone, an amphetamine-type stimulant (Shanks et al, 2012; Spiller et al, 2011). Figure 1 illustrates the chemical structures of three popular bath salts compounds: 4-methylmethcathinone (mephedrone), 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV). Owing to the public health risks posed by bath salts, the US government placed mephedrone, methylone and MDPV into Schedule I control in November 2011 (DEA, 2011). Unfortunately, a new wave of cathinone derivatives has appeared in the marketplace to replace those drugs now subject to regulatory control (Shanks et al, 2012). Figure 1 Chemical structures of bath salts cathinones and related compounds. Despite the widespread use of bath salts, there is a paucity of information about their pharmacology. Using assay methods in rat brain synaptosomes, it has been shown that mephedrone and methylone act as substrates at plasma membrane transporters for norepinephrine, dopamine, and serotonin, thereby stimulating non-exocytotic release of these neurotransmitters (Baumann et al, 2012). Mephedrone is about two-times more potent than methylone as a transporter substrate. In vivo microdialysis studies in rats confirm that mephedrone and methylone (0.3 or 1.0 mg/kg, i.v.) increase extracellular levels of dopamine and serotonin in the brain, similar to the effects of MDMA. Little is known about the pharmacology of MDPV, but our unpublished findings show the drug is a potent blocker of dopamine and norepinephrine uptake. The fact that synthetic cathinones enhance dopamine transmission predicts high abuse liability. Hadlock et al (2011) reported that i.v. mephedrone (0.24 mg/infusion) is readily self-administered by rats, but reinforcing effects of other synthetic cathinones are largely unexplored. Few preclinical studies have examined the pharmacokinetics and metabolism of synthetic cathinones or the consequences of chronic drug dosing, and these types of investigations are needed. Serotonin transporter substrates like MDMA are known to produce sustained deficits in brain serotonin neurons of laboratory animals, so mephedrone and methylone could have similar actions. Repeated subcutaneous (s.c.) administration of either drug to single-housed rats (3 or 10 mg/kg, three doses) has no long-lasting effects on brain tissue monoamines (Baumann et al, 2012), but administration of higher doses of mephedrone to group-housed rats (10 or 25 mg/kg, s.c., four doses) causes selective depletion of brain serotonin (Hadlock et al, 2011). It is noteworthy that MDPV is the chief substance detected in blood and urine from patients hospitalized for bath salts overdose in the US (Spiller et al, 2011). Such patients display agitation, combative behavior, hallucinations, delusions, hyperthermia, tachycardia and hypertension (Prosser and Nelson, 2012; Spiller et al, 2011). Health care workers should be aware that patients presenting with this constellation of symptoms may have taken bath salts, and appropriate supportive care should be provided. Owing to the increasing availability of ‘replacement' cathinones with unknown pharmacology (Shanks et al, 2012), it seems likely that emergency departments will continue to encounter patients suffering from adverse effects of synthetic cathinone abuse.

Amphetamine modifies ethanol intake of psychosocially stressed male rats

Studies of socially housed rodents have provided significant information regarding the consequences of exposure to stressors. Psychosocial stressors are known to alter the ingestion of ethanol and the activity of the dopaminergic neuronal system. Since both stressors and ethanol are known to affect the function of dopaminergic neurons, we employed amphetamine to assess the role of this neural system on the ingestion of ethanol by psychosocially stressed male rats. Male rats housed two per cage were designated as dominant or subdominant rats based on evaluations of agonistic behavior and body weight changes. The dyad-housed rats and a group of single-housed rats were sequentially assessed for ethanol intake after injections of saline or amphetamine (0.3, 0.9 or 2.7mg/kg i.p.) both prior to dyad housing and subsequently again during dyad-housing. Prior to dyad housing ethanol intake of future subdominant rats was higher than that of future dominant rats. Dyad-housing significantly increased ethanol intake of dominant rats. Pre-dyad the highest dose of amphetamine potently depressed ethanol ingestion. Sensitivity to amphetamine's depressant effect on ethanol intake was higher at the dyad test in all subjects, most prominently in single-housed rats. In contrast to the single-housed rats, the dyad-housed rats displayed saccharin anhedonia. It can be concluded that dopaminergic system modulates, at least partially, the psychosocial stress-induced changes in ethanol intake. Furthermore, the level of ethanol ingestion at the pre-dyad test was predictive of future hierarchical status.

Juvenile play conditions sexual partner preference in adult female rats

Rats can display a conditioned partner preference for individuals that bear an odor previously associated with sexual reward. Herein we tested the possibility that odors associated with the reward induced by social play in prepubescent rats would induce a conditioned partner preference in adulthood. Two groups of 31-day-old, single-housed female rats were formed, and were given daily 30-min periods of social play with scented females. In one group, almond scent was paired with juvenile play during conditioning trials, whereas lemon scent functioned as a novel odor in the final test. The counterbalanced group received the opposite association. At age 42, females were tested for play partner preference with two males, one almond-scented and one lemon-scented. In both groups females displayed a play partner preference only for males scented with the paired odor. They were ovariectomized, hormone-primed, and at age 55 were tested for sexual partner preference with two scented stud males. Females displayed a sexual preference towards males scented with the paired odor as observed with more visits, solicitations, hops and darts, intromissions and ejaculations. These results indicate that olfactory stimuli paired with juvenile play affects later partner choice for play as well as for sex in female rats.

Differential sensitivity to amphetamine’s effect on open field behavior of psychosocially stressed male rats

Studies of socially housed rodents have provided significant information regarding the mechanisms of stress and of stress-related disorders. Since psychosocial stress is known to alter the functional activity of dopaminergic system, we employed amphetamine (AMP) to evaluate the involvement dopamine in mediating the behavioral consequences of psychosocial stress. Male rats housed two per cage were designated as dominant (DOM) or subdominant (Sdom) based on initial evaluations of agonistic behaviors and body weight changes. Diad-housed rats and a group of single-housed (SiH) rats were tested in an open field after injections of saline or amphetamine (0.9 or 2.7 mg/kg IP) prior to and again while diad-housing. Compared to future DOM rats, saline-injected future Sdom rats entered the open field center less frequently, spent less time in rearing behavior and groomed less. At the pre-diad test AMP treatment elevated locomotor activity of all rats, while stimulation of center entries was more marked in future DOM rats. At the diad test, AMP's locomotor stimulant effect was evident in all experimental groups with DOM rats showing higher effects compared to Sdom and SiH rats. Amphetamine's stimulation of center entries in DOM rats was similar to the pre-diad test, but it was diminished in Sdom rats, while stimulation of rearing behavior was most evident in diad-housed rats. The dopaminergic system modulates the psychosocial stress-induced differences in explorative and emotional behaviors. Furthermore, behavioral traits like frequency of grooming behavior and of center entries were predictive of future hierarchical status.

Acute novel stressors modify ethanol intake of psychosocially stressed rats

Psychosocial stressors are known to alter ingestion of ethanol in humans and experimental animals. We evaluated the effect of novel acute stressors on ethanol ingestion of male triad-housed rats. Based on behavioral and body weight assessments triad members were designated as dominant, subdominant or subordinate rats, housed in triads designated as aggressive or non-aggressive triads. The triad-housed, and a group of single-housed rats, were sequentially subjected to three stressors (novel open field arena, elevated plus maze, and modified resident–intruder test) at 1–2 week intervals. Ethanol intake was measured for 21-h before and after each stressor. Prior to stressor exposure, ethanol intake of the triad-housed rats was higher than that of single-housed rats. In triads overall intake of ethanol was lower in dominant compared to non-dominant rats. The modified resident–intruder test decreased ethanol intake in non-dominant rats in aggressive triads, but increased its intake in non-aggressive triads. Since in non-dominant rats this stressor also increased ethanol preference but not total fluid intake, its effect on ethanol intake was specific. In non-dominant rats ethanol intake and preference declined after the elevated plus maze stressor, without an effect on total fluid intake, but water intake was increased only in the subdominant rats. Compared to triad-housed rats, single-housed rats were more resilient to the novel stressors. It can be concluded that novel acute stressors have specific effects on ethanol intake that are dependent on the subject's psychosocial stress level.

Psychosocial Stress and Volatile Compounds in Preputial Glands of Rats

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.

Psychosocial stress and chronic ethanol ingestion in male rats: Effects on elevated plus maze behavior and ultrasonic vocalizations

Psychosocial stress is known to enhance anxiety levels in rodents. The present study evaluated the effect of long-term ingestion of ethanol (EtOH) on anxiety levels of male Long Evans rats housed either singly or in triads (three/cage). Based on measures of offensive and defensive behaviors, triad-housed rats were designated as being dominant, subdominant or subordinate. The effect of chronic ingestion of a 6% EtOH solution was assessed on behaviors in the elevated plus maze (EPM) test, and on air-puffs elicited 22 kHz ultrasonic vocalizations (USV). EtOH naïve dominant rats showed less anxiogenic-like (open arms time) and displacement behavior (grooming), but more risk assessment behavior (stretch-attend postures) than their cage-mates or the single-housed rats. Intake of EtOH prior to the EPM test was lower in dominant and single-housed rats compared to subdominant and subordinate rats. Triad-housed rats, but not the single-housed rats, decreased their intake of EtOH after the EPM test. Overall, EtOH intake had an anxiolytic effect in all rats, but the effect was most prominent in single-housed rats. Furthermore, EtOH intake decreased air-puff induced USVs of triad-housed rats, but increased USVs of single-housed rats. These data indicate that housing condition and rank status influence the emotional state of male rats. Furthermore, the anxiolytic effect of voluntarily ingested EtOH was depended on these variables.