Anxiety states induced by post-weaning social isolation are mediated by CRF receptors in the dorsal raphe nucleus

Post-weaning social isolation of rats is utilized as a model of early life stress. We have previously demonstrated that rats exposed to post-weaning social isolation exhibit greater anxiety-like behaviors as adults. Furthermore, these rats exhibit greater density of corticotropin-releasing factor (CRF) type 2 receptors in the dorsal raphe nucleus. Therefore, we examined whether antagonism of CRF₂ receptors in the dorsal raphe nucleus reverses the effects of post-weaning social isolation on anxiety states. Male rats were reared in isolation or in groups from day of weaning (postnatal day [PND] 21) to mid-adolescence (PND42) and then allowed to develop to early adulthood housed in groups. At PND62, rats were either infused with vehicle, the CRF₁ receptor antagonist antalarmin (0.25-0.5μg) or the CRF₂ receptor antagonist antisauvagine-30 (2μg) into the dorsal raphe nucleus, 20min prior to being introduced to the elevated plus maze. Isolation-reared rats showed reduced open arm behavior compared to group-reared rats, confirming the anxiogenic effects of post-weaning social isolation. Infusion of the CRF₂ receptor antagonist, but not the CRF₁ receptor antagonist, into the dorsal raphe nucleus of isolation-reared rats increased open arm behavior when compared to that of group-reared rats. Overall, the findings suggest that CRF₂ receptors within the dorsal raphe nucleus mediate anxiety-like states following post-weaning social isolation, and CRF₂ receptors may represent an important target for the treatment of anxiety disorders following early life stressors.