Differential effects of site‐specific knockdown of estrogen receptor α in the medial amygdala, medial pre‐optic area, and ventromedial nucleus of the hypothalamus on sexual and aggressive behavior of male mice

Testosterone is known to play an important role in the regulation of male‐type sexual and aggressive behavior. As an aromatised metabolite of testosterone, estradiol‐induced activation of estrogen receptor α ( ER α) may be crucial for the induction of these behaviors in male mice. However, the importance of ER α expressed in different nuclei for this facilitatory action of testosterone has not been determined. To investigate this issue, we generated an adeno‐associated virus vector expressing a small hairpin RNA targeting ER α to site‐specifically knockdown ER α expression. We stereotaxically injected either a control or ER α targeting vector into the medial amygdala, medial pre‐optic area ( MPOA ), or ventromedial nucleus of the hypothalamus ( VMN ) in gonadally intact male mice. Two weeks after injection, all mice were tested biweekly for sexual and aggressive behavior, alternating between behavior tests each week. We found that suppressing ER α in the MPOA reduced sexual but not aggressive behavior, whereas in the VMN it reduced both behaviors. Knockdown of ER α in the medial amygdala did not alter either behavior. Additionally, it was found that ER α knockdown in the MPOA caused a parallel reduction in the number of neuronal nitric oxide synthase‐expressing cells. Taken together, these results indicate that the testosterone facilitatory action on male sexual behavior requires the expression of ER α in both the MPOA and VMN , whereas the testosterone facilitatory action on aggression requires the expression of ER α in only the VMN .