Dopamine in the nucleus accumbens modulates the memory of social defeat in Syrian hamsters (Mesocricetus auratus)

Gray, Cloe L; Norvelle, Alisa; Larkin, Tony E.; Huhman, Kim L.

doi:10.1016/j.bbr.2015.02.030

Cited by 40 publications

(31 citation statements)

References 67 publications

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“…In the social interaction test, one restrained animal briefly showed submissive behavior toward the intruder, and several restrained animals displayed aggressive behavior. These data are similar to agonistic behavior displayed by non-stressed hamsters in a resident-intruder paradigm, and indicate that acute restraint stress does not alter subsequent agonistic behavior [16, 19, 34, 37]. In the other behavioral tests, restrained animals tended to differ from non-restrained controls on some measures, but not always in a direction that would be considered anxiety-like.…”

Section: Resultssupporting

confidence: 67%

Dominance status alters restraint-induced neural activity in brain regions controlling stress vulnerability

Cooper

Seddighi

Barnes

et al. 2017

Physiology & Behavior

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Understanding the cellular mechanisms that control resistance and vulnerability to stress is an important step toward identifying novel targets for the prevention and treatment of stress-related mental illness. In Syrian hamsters, dominant and subordinate animals exhibit different behavioral and physiological responses to social defeat stress, with dominants showing stress resistance and subordinates showing stress vulnerability. We previously found that dominant and subordinate hamsters show different levels of defeat-induced neural activity in brain regions that modulate coping with stress, although the extent to which status-dependent differences in stress vulnerability generalize to non-social stressors is unknown. In this study, dominant, subordinate, and control male Syrian hamsters were exposed to acute physical restraint for 30 minutes and restraint-induced c-Fos immunoreactivity was quantified in select brain regions. Subordinate animals showed less restraint-induced c-Fos immunoreactivity in the infralimbic (IL), prelimbic (PL), and ventral medial amygdala (vMeA) compared to dominants, which is consistent with the status-dependent effects of social defeat stress. Subordinate animals did not show increased c-Fos immunoreactivity in the rostroventral dorsal raphe nucleus (rvDRN), which is in contrast to the effects of social defeat stress. These findings indicate that status-dependent changes in neural activity generalize from one stressor to another in a brain region-dependent manner. These findings further suggest that while some neural circuits may support a generalized form of stress resistance, others may provide resistance to specific stressors.

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Section: Resultssupporting

confidence: 67%

Dominance status alters restraint-induced neural activity in brain regions controlling stress vulnerability

Cooper

Seddighi

Barnes

et al. 2017

Physiology & Behavior

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“…Our customary defeat procedure uses a 15 min, inescapable defeat. This is a relatively mild social stressor, but it is sufficient to lead to robust and quantifiable behavioral changes observed during subsequent testing (Gray et al, 2015; Jasnow and Huhman, 2001; McCann and Huhman, 2012). In our original experiment, we did not observe a change in social avoidance in animals given VPA, but this could be due to a ceiling effect.…”

Section: Discussionmentioning

confidence: 99%

Histone deacetylase and acetyltransferase inhibitors modulate behavioral responses to social stress

McCann

Rosenhauer

Jones

et al. 2017

Psychoneuroendocrinology

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Histone acetylation has emerged as a critical factor regulating learning and memory both during and after exposure to stressful stimuli. There are drugs that we now know affect histone acetylation that are already in use in clinical populations. The current study uses these drugs to examine the consequences of acutely increasing or decreasing histone acetylation during exposure to social stress. Using an acute model of social defeat in Syrian hamsters, we systemically and site-specifically administered drugs that alter histone acetylation and measured subsequent behavior and immediate-early gene activity. We found that systemic administration of a histone deacetylase inhibitor enhances social stress-induced behavioral responses in males and females. We also found that systemic administration completely blocks defeat-induced neuronal activation, as measured by Fos-immunoreactivity, in the infralimbic cortex, but not in the amygdala, after a mild social defeat stressor. Lastly, we demonstrated that site-specific administration of histone deacetylase inhibitors in the infralimbic region of the prefrontal cortex, but not in the basolateral amygdala, mimics the systemic effect. Conversely, decreasing acetylation by inhibiting histone acetyltransferases in the infralimbic cortex reduces behavioral responses to defeat. This is the first demonstration that acute pharmacological manipulation of histone acetylation during social defeat alters subsequent behavioral responses in both males and females. These results reveal that even systemic administration of drugs that alter histone acetylation can significantly alter behavioral responses to social stress and highlight the importance of the infralimbic cortex in mediating this effect.

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“…Together, these findings strongly suggest that the effect of noradrenergic manipulations on aggression is mediated centrally, although more research is needed to determine where centrally the effects of social defeat on aggression are mediated. Previous research from our lab demonstrated that infusion of a GABA A receptor agonist (Luckett et al, 2012) or a dopamine receptor antagonist (Gray et al, 2015) into the nucleus accumbens before testing also restored aggression in previously defeated hamsters, so it is possible that the nucleus accumbens in a component of this circuit. Finally, we have demonstrated that the pharmacological inactivation of the lateral septum using muscimol also increases aggression in previously defeated hamsters, but it is important to note that this effect was limited to expression and not acquisition of CD and muscimol in the lateral septum increased aggression independent of whether the animals had been previously defeated or not (McDonald et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Immediate post-defeat infusions of the noradrenergic receptor antagonist propranolol impair the consolidation of conditioned defeat in male Syrian hamsters

Gray

Krebs-Kraft

Solomon

et al. 2015

Physiology & Behavior

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Summary Social defeat occurs when an animal is attacked and subjugated by an aggressive conspecific. Following social defeat, male Syrian hamsters fail to display species-typical territorial aggression and instead exhibit submissive or defensive behaviors even when in the presence of a non-aggressive intruder. We have termed this phenomenon conditioned defeat (CD). The mechanisms underlying CD are not fully understood, but data from our lab suggest that at least some of the mechanisms are similar to those that mediate classical fear conditioning. The goal of the present experiment was to test the hypothesis that noradrenergic signaling promotes the consolidation of CD, as in classical fear conditioning, by determining whether CD is disrupted by post-training blockade of noradrenergic activity. In Experiment 1, we determined whether systemic infusions of the noradrenergic receptor antagonist propranolol (0, 1.0, 10, or 20 mg/kg) given immediately after a 15 min defeat by a resident aggressor would impair CD tested 48h later. Hamsters that were given immediate post-training infusions of propranolol (1.0, but not 10 or 20 mg/kg) showed significantly less submissive behavior than those given vehicle infusions supporting the hypothesis that there is noradrenergic modulation of social defeat consolidation. In Experiment 2, we demonstrated that propranolol (1.0 mg/kg) given immediately, but not 4 or 24h, after defeat impaired CD tested 48h after defeat indicating that the window within which the memory for social defeat is susceptible to beta-adrenergic modulation is temporary. In Experiment 3, we examined whether central blockade of noradrenergic receptors could recapitulate the effect of systemic injections by giving an intracerebroventricular infusion of propranolol immediately after defeat and examining the effect on CD 24 h later. Centrally administered propranolol (20 μg/3μl but not 2 μg/3μl) was also effective in dose-dependently reducing consolidation of CD. Collectively, the present results indicate that noradrenergic activity promotes the consolidation of CD and suggest that CD is a valuable model to study the processes by which emotion and stress modulate memory in an ethologically relevant context. These data also suggest that the popular conception in the clinical literature that the anxiolytic effect of propranolol is primarily due to the drug’s peripheral effects may need to be reconsidered.

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Dopamine in the nucleus accumbens modulates the memory of social defeat in Syrian hamsters (Mesocricetus auratus)

Cited by 40 publications

References 67 publications

Dominance status alters restraint-induced neural activity in brain regions controlling stress vulnerability

Dominance status alters restraint-induced neural activity in brain regions controlling stress vulnerability

Histone deacetylase and acetyltransferase inhibitors modulate behavioral responses to social stress

Immediate post-defeat infusions of the noradrenergic receptor antagonist propranolol impair the consolidation of conditioned defeat in male Syrian hamsters

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