Defeat-induced activation of the ventral medial prefrontal cortex is necessary for resistance to conditioned defeat

Abstract

The ventral medial prefrontal cortex (vmPFC) controls vulnerability to the negative effects of chronic or uncontrollable stress. Dominance status alters responses to social defeat in the conditioned defeat model, which is a model characterized by loss of territorial aggression and increased submissive and defensive behavior following an acute social defeat. We have previously shown that dominant individuals show a reduced conditioned defeat response and increased defeat-induced neural activation in the vmPFC compared to subordinates. Here, we tested the hypothesis that defeat-induced activation of the vmPFC is necessary to confer resistance to conditioned defeat in dominants. We paired weight-matched male Syrian hamsters (Mesocricetus auratus) in daily 5-min aggressive encounters for two weeks and identified dominants and subordinates. Twenty-four hours after the final pairing, animals were bilaterally injected with 200 nl of the GABAA receptor agonist muscimol (1.1nmol) or 200 nl of saline vehicle 5 minutes prior to social defeat. Defeat consisted of 3, 5-min encounters with resident aggressor hamsters at 10-min intervals. Twenty-four hours following social defeat, animals received conditioned defeat testing which involved a 5-min social interaction test with a non-aggressive intruder. Muscimol injection prior to social defeat prevented the reduced conditioned defeat response observed in vehicle-treated dominants. Further, there was no effect of muscimol injection on the conditioned defeat response in subordinates or controls. These data support the conclusion that activation of the vmPFC during social defeat is necessary for the protective effects of dominant social status on the acquisition of conditioned defeat.

Maintenance of dominance status is necessary for resistance to social defeat stress in Syrian hamsters

“…In previous studies, we have found that dominant individuals initially respond to social defeat by counter attacking their opponent [4, 36]. Similar to conditioned defeat behavior, the incidence of counter attacking was influenced by the duration of dominance relationship, with 7 day and 14 day dominants showing significantly more counter attacking of resident aggressors than corresponding subordinates and controls.…”

“…IL lesions prior to environmental enrichment prevent resistance to chronic social defeat, while IL lesions prior to social defeat do not, suggesting that the IL is responsible for the development but not expression of stress resistance. In contrast, pharmacological inactivation of the vmPFC prior to social defeat or uncontrollable tail shock blocks the formation of conditioned defeat and learned helplessness, respectively [18, 36, 42]. Overall, these differences between models suggest that social and physical experiences generate stress resistance via separate cellular and molecular mechanisms in the PL and IL.…”

Social play in juvenile hamsters alters dendritic morphology in the medial prefrontal cortex and attenuates effects of social stress in adulthood.

“…We have shown that dominant hamsters exhibit a reduced conditioned defeat response compared to subordinates and controls and also exhibit elevated c-Fos expression in the PL and IL cortices (Morrison, et al, 2014; Morrison, et al, 2012). In addition, pharmacological inactivation of the vmPFC during social defeat stress prevents the reduced conditioned defeat response of dominant animals (Morrison, et al, 2013). Altogether, our findings suggest that play deprivation impairs dendritic morphology in the vmPFC and that dysregulated vmPFC neural activity in adulthood may potentiate the effects of social defeat stress.…”

Winning agonistic encounters increases testosterone and androgen receptor expression in Syrian hamsters

“…Specifically, we use conditioned defeat, a social stress model in Syrian hamsters in which a brief social defeat stress results in a loss of species-typical territorial aggression and an increase in submissive and defensive behavior when animals are later tested with a small, nonaggressive intruder (Huhman et al, 2003; Potegal et al, 1993). We have previously shown that pairs of Syrian hamsters with established dominance relationships respond differently to social defeat stress, such that dominant animals show a reduced conditioned defeat response compared to subordinate counterparts (Morrison et al, 2014; Morrison et al, 2013; Morrison et al, 2012; Morrison et al, 2011). However, hamsters must maintain social dominance for 14 days, and not for 1 or 7 days to exhibit resistance to conditioned defeat (Morrison et al, 2014).…”