Sex-dependent modulation of anxiety and fear by 5-HT1A receptors in the bed nucleus of the stria terminalis

Serotonin (5-hydroxytryptamine; 5-HT) coordinates behavioral responses to stress through a variety of presynaptic and postsynaptic receptors distributed across functionally diverse neuronal networks in the central nervous system. Efferent 5-HT projections from the dorsal raphe nucleus (DRN) to the bed nucleus of the stria terminalis (BNST) are generally thought to enhance anxiety and aversive learning by activating 5-HT2C receptor (5-HT2CR) signaling in the BNST, although an opposing role for postsynaptic 5-HT1A receptors has recently been suggested. In the present study, we sought to delineate a role for postsynaptic 5-HT1A receptors in the BNST in aversive behaviors using a conditional knockdown of the 5-HT1A receptor. Both males and females were tested to dissect out sex-specific effects. We found that male mice have significantly reduced fear memory recall relative to female mice and inactivation of 5-HT1A receptor in the BNST increases contextual fear conditioning in male mice so that they resemble t...