Serotonin-specific lesions of the dorsal raphe disrupt maternal aggression and caregiving in postpartum rats

The behavioral modifications associated with early motherhood, which include high aggression, caring for the young, and low anxiety, are all affected by acute pharmacological manipulation of serotonin signaling. However, the effects on all these behaviors of permanently disrupting serotonin signaling from one of its primary sources, the dorsal raphe nucleus (DR), have not been examined in detail. To address this, serotonin-specific lesions centered on the dorsomedial DR (DRdm; DR subregion strongly implicated in emotional behaviors) were induced at mid-pregnancy (day 15) or early postpartum (day 2) in rats using a saporin-conjugated neurotoxin targeting the serotonin transporter (Anti-SERT-SAP). Prepartum or postpartum Anti-SERT-SAP reduced DRdm serotonin immunoreactivity by ∼40-65%, and postpartum Anti-SERT-SAP also reduced it in the ventromedial and lateral wings of the DR, as well as in the median raphe. Serotonin-immunoreactive fibers were significantly reduced in the anterior hypothalamus, but not medial preoptic area, of lesioned dams. Pre- or postpartum lesions both greatly reduced maternal aggression, but while prepartum lesions did not affect later undisturbed maternal caregiving, the larger postpartum lesions prevented the postpartum decline in kyphotic nursing and reduced pup licking. Serotonin lesions did not affect pup retrieval, but the prepartum lesions temporarily increased maternal hovering over and licking the pups observed immediately after the disruptive retrieval tests. Dams' anxiety-like behaviors and litter weight gains were unaffected by the lesions. These findings suggest that DRdm serotonin projecting to the AH is particularly critical for maternal aggression, but that more widespread disruption of midbrain raphe serotonin is necessary to greatly impair maternal caregiving. Postpartum anxiety may rely more on other neurochemical systems or different midbrain serotonergic cell populations.