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

Abstract

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.

Keywords: Aggression; Anxiety; Lactation; Maternal behavior; Pregnancy; Serotonin.

Figure 1

Schematic representation of the experimental time course used to determine the effects of prepartum (top) and postpartum (bottom) Anti-SERT-SAP lesions of the DR on postpartum behaviors. EPM = elevated plus maze, LD = light-dark box.

Figure 2

Representative photomicrograph of the DR after prepartum infusion of the control conjugate (A,B) or Anti-SERT-SAP (C,D). Relative optical density (Mean + SEM) of serotonin immunoreactivity in the DR from the (E) prepartum and (F) postpartum experiments. DRdm = dorsomedial subregion of the DR, DRvm = ventromedial subregion of the DR, DRlw = lateral wings of the DR, DRc = caudal DR. Scale bar = 100 μm. *p < 0.05.

Figure 3

Total length (Mean + SEM) of serotonin-ir fibers in the AH and mPOA of prepartum control and Anti-SERT-SAP lesioned rats. *p < 0.05.

Figure 4

Frequency (Mean + SEM) of (A) kyphosis and (B) supine nursing during undisturbed observations of maternal behavior by postpartum-lesioned and control dams. Frequency of (C) hovering over pups and (D) licking pups by prepartum-lesioned and control dams during 10-minute observations after retrieval tests. *p < .05.

Figure 5

Total attack duration (Mean + SEM) by dams in the (A) prepartum experiment and (B) postpartum experiment. Average duration of attack bouts (Mean + SEM) in the (C) prepartum experiment and (D) postpartum experiment. *p < 0.05, ^#p = 0.07.