Does lateral habenula mediate effects of gestational stress on rat maternal behavior?

This exploratory study investigated the neural substrate underlying the effect of gestational stress on rat maternal behavior. We tested the hypothesis that the lateral habenula (LHb)-centered neural circuitry (e.g., raphe, ventral tegmental area, nucleus accumbens, etc.) mediates the maternal disruptive effect of gestational stress. Pregnant Sprague-Dawley rats were subjected to daily 30-min restraining stress from approximately gestation day (GD) 5 to 21, white noise from GD 5 to 12 and mild foot shock from GD 13 to 21. Maternal behavior in the home cage and pup retrieval on an elevated plus maze (EPM) were observed during the first postpartum week. The gestational stress reduced body weight gain of stressed females, and reduced time that they spent outside of the nest, a sign of increased maternal anxiety and hypervigilant parenting style. On the open arms of EPM, the stressed dams showed higher frequently sniffing pups than non-stressed ones. Testing with pups (pup exposure) on the EPM decreased c-Fos expression in the LHb in the non-stressed control dams, but it increased c-Fos expression in the dorsal and medial raphe regions of the control dams. Gestational stress reduced this pup effect in all three regions, implying that gestational stress attenuated the ability of pup exposure to activate the maternally relevant brain regions. Our findings indicate that gestational stress may act upon the LHb (as a putative center that mediates negative emotion) and its downstream projection sites (i.e., dorsal and median raphe) to compromise the quality of maternal care.