Oxytocin receptors in the midbrain dorsal raphe are essential for postpartum maternal social and affective behaviors.

Oxytocin receptors (OTRs) in the midbrain dorsal raphe (DR; the source of most forebrain serotonin) have recently been identified as a potential pharmacological target for treating numerous psychiatric disorders. However, almost all research on this topic has been conducted on males and the role of DR OTRs in female social and affective behaviors is mostly unknown. This may be particularly relevant during early motherhood, which is a time of high endogenous oxytocin signaling, but also a time of elevated risk for psychiatric dysfunction. To investigate whether OTRs in the DR are necessary for postpartum female social and affective behaviors, we constructed and then injected into the DR an adeno-associated virus permanently expressing an shRNA targeting OTR mRNA. We then observed a suite of social and affective behaviors postpartum. OTR knockdown in the maternal DR led to pup loss after parturition, decreased nursing, increased aggression, and increased behavioral despair. These effects of OTR knockdown in the DR may be due to disrupted neuroplasticity in the primary somatosensory cortex (S1), which mediates maternal sensitivity to the tactile cues from young, as we found significantly more plasticity-restricting perineuronal nets (PNNs) in the S1 rostral barrel field and fewer PNNs in the caudal barrel field of OTR-knockdown mothers. These results demonstrate that OTRs in the midbrain DR are essential for postpartum maternal social and affective behaviors, are involved in postpartum cortical plasticity, and suggest that pharmacotherapies targeting OTRs in the DR could be effective treatments for some peripartum affective disorders.