Mary Karom

Social interactions tune aggression and stress responsiveness in a territorial cichlid fish (Archocentrus nigrofasciatus)

We examined the relative influences of pre-fight housing condition, contest intensity, and contest outcome in modulating post-fight stress hormone concentrations in territorial male convict cichlids (Archocentrus nigrofasciatus). Individuals were housed either in isolation or in semi-natural communal tanks. Pairs of male cichlids that differed considerably in body mass were selected from the same housing regime. Pre-fight water-borne cortisol levels were obtained before allowing the dyad to interact until contest resolution, after which time post-fight cortisol levels were obtained from the winner and loser. There were no outcome-related differences in post-fight cortisol concentrations following escalated or non-escalated contests, a result that held true for both housing regimes. Pre-fight cortisol levels were significantly higher than post-fight cortisol levels, suggesting that initial confinement in a beaker for the water-borne hormone samples was a stressor, but that the animals acclimated quickly to confinement. Fights involving previously isolated participants were significantly more intense than those involving group-housed animals, which we explain as being a function of established relationships between social isolation, heightened acute cortisol responsiveness, and the expression of excessive aggressive behavior. Only group-housed losers demonstrated the ability to modulate aggression or hypothalamic-pituitary-interrenal (HPI) activity in a graded fashion to acute increases in cortisol or changes in contest intensity, respectively. We discuss a variety of factors that could disrupt the ability of isolates to appropriately modulate interactions between social behavior and the HPI axis, and we examine a number of functional hypotheses underlying the sensitivity of group-housed losers to changes in contest dynamics.

Arginine-vasopressin and the regulation of aggression in female Syrian hamsters (Mesocricetus auratus)

Arginine‐vasopressin (AVP) is critical for the expression of a variety of social behaviors in many species. Previous studies have demonstrated that AVP regulates behaviors such as social communication and aggression in Syrian hamsters through the V1a receptor subtype. In male hamsters, AVP injected into the anterior hypothalamus (AH) stimulates aggression, while injection of a V1a receptor antagonist inhibits the behavior. The purpose of the present studies was to determine whether AVP influences aggression by its action in the AH in female hamsters. In the first experiment, we were surprised to find that injection of the V1a receptor antagonist, Manning compound, into the AH of intact female hamsters increased aggression. The second experiment confirmed the ability of the V1a receptor antagonist to increase aggression and found that the largest effects of the antagonist occurred at intermediate concentrations of the compound. The next experiment found that injection of AVP into the AH significantly reduced the latency to attack and the duration of aggression. Finally, we examined whether the effects of AVP and the V1a receptor antagonist on aggression differed in hamsters exposed to long ‘summer‐like’ photoperiods or short ‘winter‐like’ photoperiods, and found that their effects on aggression were not photoperiod dependent. In summary, contrary to what is observed in males, these data suggest that AVP in the AH may play an inhibitory role on aggression in female Syrian hamsters.

Role of V1a vasopressin receptors in the control of aggression in Syrian hamsters.

The present study investigated the hypothesis that social isolation increases aggression by increasing the number of V1a vasopressin receptors in the anterior hypothalamus (AH). Male hamsters were randomly assigned to a group that was allowed to interact with a small nonaggressive hamster three times each week for 3 weeks (socially experienced) or to a group that did not interact socially with other hamsters (social isolates). On the final day of the experiment, hamsters in both groups were placed in a neutral arena with a small, nonaggressive intruder, and agonistic behavior was scored for 10 min. In social isolates, the duration of aggression and the number of attacks were significantly greater than in socially experienced hamsters. There were no significant between-group differences in the latency to the onset of aggression, the number of flank marks or in the duration of defensive/submissive, social or nonsocial behavior. The amount of V1a receptor binding was significantly greater in the AH, the paraventricular nucleus of the hypothalamus and the lateral hypothalamus in the social isolates than in the socially experienced hamsters. The amount of V1a receptor binding was significantly greater in the central amygdala of socially experienced hamsters than in socially isolated hamsters. Serum concentrations of testosterone were significantly higher in the socially experienced hamsters than in social isolates. These data support the hypothesis that social isolation increases aggression by increasing the number of V1a vasopressin receptors in the AH.

Repeated agonistic encounters in hamsters modulate AVP V1a receptor binding

Arginine vasopressin (AVP) regulates aggression in male Syrian hamsters. In this study, we used radioligand receptor autoradiography to examine whether changes in agonistic behavior following acute and repeated social defeat are accompanied by changes in AVP V1a receptor binding. Social defeat produced high levels of submissive behavior and a loss of territorial aggression when hamsters were subsequently tested with a novel intruder, and repeated agonistic encounters produced similar behavioral changes in subordinates. AVP V1a receptor binding was not reduced by acute social defeat but was affected by repeated agonistic encounters. Dominants had significantly more AVP V1a receptor binding in lateral portions of the ventromedial hypothalamus (VMHL) than did their subordinate opponents, but subordinates were no different from controls. In contrast, receptor binding did not differ in most other brain regions examined. The changes in receptor binding appear to be independent of testosterone levels, as testosterone levels did not differ among dominants, subordinates, and controls. Our results suggest that changes in AVP V1a receptors do not account for the changes in agonistic behavior produced by acute social defeat but AVP V1a binding in the VMHL correlates with, and may modulate, the behavioral changes that occur following repeated experiences of victory.

Sex and estrous cycle differences in the display of conditioned defeat in Syrian hamsters.

We have reported that there is a sex difference in the behavioral response to social defeat in hamsters. While previously defeated male hamsters fail to display normal territorial aggression and instead produce submissive/defensive behavior, a phenomenon that we have termed conditioned defeat (CD), only a small portion of previously defeated females exhibit CD. In Experiment 1, we tested the hypothesis that CD varies over the estrous cycle and found that previously defeated female hamsters tested on diestrus 2 and proestrus were more likely to exhibit CD than were females tested on diestrus 1 and estrus. In Experiment 2, we found that regardless of hormonal status, non-defeated females displayed normal territorial aggression, indicating that the behavioral changes observed in Experiment 1 were not due to a cyclic variation in submissive behavior independent of a previous defeat encounter. In Experiment 3, we found that females tested 4 days after defeat responded similarly to those tested 1 day after defeat suggesting that the hormonal status of females on the day of testing is a more important determinant of the behavioral response to defeat than is the hormonal status on the day of defeat training. Finally, in Experiment 4, we monitored anxiety-like behaviors in diestrous 1 and proestrous females in an open field arena and found that there was no effect of cycle on any of the observed behavioral measures, suggesting that the observed differences in CD are not the result of differences in generalized anxiety-like behaviors across the estrous cycle.

GABAA receptor activation suppresses Period 1 mRNA and Period 2 mRNA in the suprachiasmatic nucleus during the mid-subjective day.

The mammalian circadian clock can be entrained by photic and nonphotic environmental time cues. γ‐aminobutyric acid (GABA) is a nonphotic stimulus that induces phase advances in the circadian clock during the middle of the subjective day. Several nonphotic stimuli suppress Period 1‐ and Period 2 mRNA expression in the suprachiasmatic nucleus (SCN); however, the effect of GABA on Period mRNA is unknown. In the present study we demonstrate that microinjection of the GABAA receptor agonist muscimol into the SCN region suppresses the expression of Period 1 mRNA in the hamster. A significant suppression of Period 2 mRNA following microinjection of muscimol was not observed in free‐running conditions. However, Period 2 mRNA was significantly reduced following muscimol treatment when animals were maintained under a light cycle and transferred to constant darkness 42 h prior to treatment. An additional study investigated the maximum behavioural phase advance inducible by GABAA receptor activation.Together, these data indicate that, like other nonphotic stimuli, GABA suppresses Period 1‐ and Period 2 mRNA in the SCN.

Serotonin and vasopressin interact in the hypothalamus to control communicative behavior.

&NA; The present study investigated whether serotonin (5‐HT) agonists could inhibit the ability of arginine‐vasopressin (AVP) to induce a form of scent marking called flank marking by their actions in the medial preoptic‐anterior hypothalamus (MPOA‐AH). DOI, a 5‐HT2A,2B,2C receptor agonist, did not inhibit AVP‐induced flank marking, but mCPP a 5‐HT2A antagonist and 5‐HT2B,2C agonist inhibited AVP‐induced flank marking. In addition, the finding that 8‐OH‐DPAT, CGS‐12066A and SC53116 also inhibited AVP‐induced flank marking suggests that 5‐HT could also inhibit flank marking by acting through 5‐HT1A, 5‐HT7, 5‐HT1B and/or 5‐HT4 receptor subtypes. These data support the hypothesis that 5‐HTacts within the MPOA‐AH to inhibit the ability of AVP to induce flank marking. NeuroReport 13:931‐933

Conversion of testosterone to estradiol may not be necessary for the expression of mating behavior in male Syrian hamsters (Mesocricetus auratus).

Male sexual behavior is mediated in part by androgens, but in several species, mating is also influenced by estradiol formed locally in the brain by the aromatization of testosterone. The role of testosterone aromatization in the copulatory behavior of male Syrian hamsters is unclear because prior studies are equivocal. Therefore, the present study tested whether blocking the conversion of testosterone to estradiol would inhibit male hamster sexual behavior. Chronic systemic administration of the nonsteroidal aromatase inhibitor Fadrozole (2.0 mg/kg/day) for 5 or 8 weeks did not significantly increase mount latency or reduce mount frequency, intromission frequency, ejaculation frequency, or anogenital investigation relative to levels shown by surgical controls. However, Fadrozole effectively inhibited aromatase activity, as evidenced by the suppression of estrogen-dependent progesterone receptor immunoreactivity in the male hamster brain. The JZB39 anti-progesterone receptor antibody labeled significantly more neurons in brains of sham-treated hamsters than in brains of Fadrozole-treated hamsters. These data suggest that aromatization of testosterone to estradiol is not necessary for normal mating behavior in Syrian hamsters.

The neurobehavioral effects of phytoestrogens in male Syrian hamsters.

We used a phytoestrogen (PE) and a phytoestrogen-free (PE-Free) diet to determine whether or not diet can have neurobehavioral effects on intermale aggression in Syrian hamsters (Mesocricetus auratus). In Experiment 1, 20 adult male hamsters were pre-tested for aggression and then placed on a PE (n=10) or a PE-Free diet (n=10) for 4 weeks in isolation. During week 5, experimental hamsters were exposed to a group-housed, nonaggressive opponent (NAO) for 5 min in a neutral cage arena. PE-fed hamsters exhibited more attacks (33.4+/-6.1) toward the NAO compared to the PE-Free-fed hamsters (18.1+/-4) (p<0.05). Interestingly, testosterone in the blood serum was higher in the PE-fed group (11.01+/-1.48 ng/ml) compared to the PE-Free group (6.5+/-0.87 ng/ml). In Experiment 2, 16 juvenile hamsters were weaned onto a PE (n=8) or a PE-Free diet (n=8). After 7 weeks on the diet, experimental hamsters were exposed to a NAO for 5 min in a neutral cage arena. Although the PE group exhibited higher levels of aggressive behavior, there were no statistically significant differences between groups. However, the PE group had higher levels of testosterone (9.0+/-0.95 ng/ml) compared to the PE-Free group (4.6+/-0.98 ng/ml) (p<0.05). In addition, analysis of the brains from both experiments revealed differences in binding for vasopressin 1A (V1A) receptors. Optical densities were converted to disintegrating units per min/mg. The PE-Free group had higher levels of V1A receptor binding (2689.93+/-254.8 dpm/mg) compared to the PE group (1907.32+/-136.3 dpm/mg) in the lateral septum (p<0.05). In addition, there were differences in the lateral hypothalamus, but the PE group had higher receptor binding (2550.9+/-63.59 dpm/mg) when compared to the PE-Free group (2011.9+/-174.14 dpm/mg) (p<0.05). In sum, these data present the first evidence that phytoestrogens can affect aggressive behavior and, concurrently, alter hormonal status and stimulate changes in the brain of male hamsters.

Role of the central amygdala in social communication in Syrian hamsters (Mesocricetus auratus).

In Syrian hamsters, vasopressin (AVP) controls a form of scent marking called flank marking. Microinjection and lesion studies have identified several components of the neural circuit controlling this behavior. Microinjection of AVP into the medial preoptic-anterior hypothalamus (MPOA-AH), lateral septal nucleus (LS), bed nucleus of stria terminalis (BNST), and periaqueductal gray (PAG) stimulates an intense bout of flank marking. Lesions of areas such as the MPOA-AH and the LS inhibit flank marking. Other studies employing Fos immunocytochemistry suggest that the central amygdala (Ce) might be a component of this neural circuit. The purpose of the present study was to assess the significance of the Ce in regulation of AVP-induced flank marking. In Expt. 1A, the Ce of hamsters were either lesioned with ibotenic acid or sham-lesioned. In Expt. 1B, the Ce of hamsters were either lesioned electrolytically or sham-lesioned. All lesions were made bilaterally. One week later, hamsters were microinjected with AVP into the MPOA-AH and immediately tested for flank marking. In Expt. 2, the hamsters were microinjected with AVP into the Ce and were immediately tested for flank marking. Ibotenic lesions of the Ce reduced flank marking and electrolytic lesions completely inhibited flank marking in response to AVP microinjected into the MPOA-AH. Sham-lesions or lesions placed in other areas of the amygdala resulted in intense bouts of AVP-induced flank marking and flank grooming. No flank marking or flank grooming was observed in response to AVP microinjected into the Ce. These data indicate that the Ce plays a critical role in AVP-induced flank marking, although flank marking is not induced by AVP within the Ce itself.