Sexually dimorphic patterns of neural activity in response to juvenile social subjugation

After experiencing juvenile social subjugation (JSS), adult female rats display more severe depression- and anxiety-like behaviors than adult males, suggesting that JSS is encoded in a sex-specific manner. To test this hypothesis, prepubertal rats (P28-33) were subjected to 10 aggressive acts in ≤10 min from an aggressive adult male, a 10 min encounter with a non-aggressive adult male, or to 10 min in an empty, clean cage (handled control) and were sacrificed one hour later. We then used unbiased stereology to estimate the total number and proportion of neurons immunoreactive for the immediate early gene product Fos bilaterally in the basolateral amygdala (BLA), the anterior and posterior subdivisions of the bed nucleus of the stria terminalis, and the paraventricular nucleus of the hypothalamus (PVN). Overall, females' Fos responses were less selective than males'. The BLA in males displayed a selective Fos response to the non-aggressive male, whereas no such selectivity occurred in the BLA of females. Additionally, there were more neurons overall in the left BLA than the right and this lateralization was specific to males. The principal subdivision of the BST (BSTpr) in males responded selectively to JSS, whereas the BSTpr in females responded to both the non-aggressive and aggressive males. We also found that the regional volume and neuron number of the BSTpr is greater in males than in females. Finally, the PVN in males was, like the BLA, selective for the non-aggressive male, whereas none of the experiences elicited a selective response in females. The greater selectivity for non-threatening stimuli in males in three stress-responsive brain regions may be a clue as to why males are less susceptible to the anxiogenic effects of JSS.