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Nucleus accumbens serotonin 1A receptor expression is altered by female reproduction and regulates postpartum affective and caregiving behaviors

Erika M. Vitale,Emma Ford,Margaret S Ahern,J. Lonstein

Published 2025 in Journal of Psychopharmacology

ABSTRACT

Background: Motherhood is often characterized by a positive affective state and high motivation to interact with potentially rewarding offspring. However, many mothers suffer from postpartum mental health issues that can degrade their maternal motivation and caregiving abilities. Serotonin-modulating drugs are commonly used to treat distressed mothers, but how serotonin (5-HT) in brain sites underlying motivation influences postpartum behaviors is mostly unknown. Aims: Because 5-HT in the nucleus accumbens (NAcs) regulates dopamine release, we hypothesized that the NAc is a critical site where serotonin signaling influences postpartum affective and caregiving behaviors. Methods: We used RT-qPCR and autoradiographic binding to determine changes in NAc 5-HT1A, 5-HT2A, and 5-HT2C receptor expression across pregnancy and postpartum; shRNA-mediated knockdown of NAc 5-HT1A receptors to determine its effects on postpartum behavior; and repeated pregnancy stress to determine its effects on both NAc 5-HT1A and postpartum behavior. Results: Recently parturient rats had higher 5-HT1A (but not 5-HT2A or 5-HT2C) receptor mRNA and 5-HT1A binding in the NAc shell (NAcSh) compared with nulliparae. 5-HT1A knockdown in the maternal NAcSh to prevent this normative increase in receptor expression resulted in high anxiety-like behavior, more off-nest behaviors, and delayed pup retrieval. 5-HT1A knockdown also reduced NAcSh tyrosine hydroxylase. Pregnancy stress reduced postpartum NAcSh 5-HT1A receptor binding at some rostrocaudal levels, as well as disrupted the display of caregiving behaviors. Conclusions: These results provide new insights into how 5-HT signaling in the NAcSh contributes to postpartum affective and caregiving behaviors and offer a mechanism through which serotonin-based pharmacotherapies may help improve maternal caregiving motivation in anxious, depressed, or chronically stressed mothers.

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