Rationale: In Syrian hamsters (Mesocricetus auratus), social defeat produces a prolonged change in subsequent agonistic behavior termed conditioned defeat. This stress-induced change in behavior is marked by increased submissive and defensive behavior toward a novel, nonaggressive opponent and a complete loss of normal territorial aggression. Corticotropin-releasing factor (CRF) has been shown to affect serotonergic neurons in the dorsal raphe nucleus (DRN) and to modulate learned helplessness via a CRF type-2 receptor (CRF-R2) mechanism.
Objectives: In this study, we tested the hypothesis that a nonselective CRF receptor antagonist (experiment 1: 250 or 500 ng D: -Phe CRF in 200 nl saline), or a selective CRF-R2 antagonist (experiment 2: 500 ng anti-Svg-30 in 200 nl saline), injected into the DRN would reduce the acquisition of conditioned defeat in male hamsters. We also tested similar hypotheses for the expression of conditioned defeat (experiments 3 and 4).
Results: Infusion of D: -Phe CRF into the DRN significantly reduced both the acquisition and expression of conditioned defeat compared to vehicle controls, whereas infusion of anti-Svg-30 into the DRN reduced expression but not acquisition. In particular, CRF antagonism in the DRN decreased fleeing from novel opponents but did not reinstate normal territorial aggression after social defeat.
Conclusions: Our results suggest that the increased flight associated with conditioned defeat is modulated by CRF-R2 activation within the DRN. Overall, social defeat is an ethologically relevant stressor that appears to activate at least some of the same neural substrates that have been implicated in the control of learned helplessness.