Mammalian mothers show a unique suite of behavioral responses beginning around the time of parturition that are necessary for successful rearing of young. These include caring for offspring, high levels of aggression, and low anxiety. These behaviors emerge in response to the unique neurochemical milieu resulting from pregnancy and parturition. Studies in this dissertation test the hypothesis that changes in receptors for the neurotransmitter serotonin (5-HT) are part of this neurochemistry in female laboratory rats. Experiments in chapter one found that there are reproductive state-dependent changes in expression of central 5-HT receptors that may be responsible for peripartum behavioral responses. Specifically, females examined at parturition and early lactation showed less serotonin 2C receptor (5-HT2C) mRNA expression in the midbrain dorsal raphe (DR), more serotonin 2A receptor (5-HT2A) mRNA in the medial preoptic area (mPOA), and more serotonin 1A (5-HT1A) mRNA in the shell subregion of the nucleus accumbens (NAcSh) compared to nulliparous females. Receptor autoradiography confirmed that binding density of 5-HT2A was higher in the mPOA of recently parturient females and that binding density of 5-HT1A in the NAcSh was higher in lactating females at particular rostrocaudal levels. Such differences in 5-HT receptor expression were not found in maternally acting virgin females, suggesting that pregnancy and parturition are necessary for these changes in central 5-HT receptors to occur. Because pregnancy stress derails most behavioral adaptations of motherhood, follow up experiments then explored whether the normative changes in 5-HT receptor expression across reproduction were prevented by daily application of mild-to-moderate stress beginning one week after mating. Stressed females showed lower maternal care and higher depression-like behaviors, which were correlated with 5-HT receptor mRNA in the mPOA, NAcSh and DR. Autoradiographic binding density of mPOA 5-HT2A receptors was not affected by pregnancy stress, although the stress reduced 5-HT1A binding in the NAcSh. Because the NAcSh is involved in motivation and reward processing, the last experiment directly tested whether 5-HT1A receptors in the NAcSh contribute to maternal caregiving and emotional behaviors. Long-term knock down of 5-HT1A in the NAcSh was established using an adeno-associated virus promoting shRNA against 5-HT1A mRNA. The 5-HT1A shRNA vector or a scrambled control vector was infused into the NAcSh during early pregnancy and mothers' later postpartum social and affective behaviors (i.e. caregiving, maternal motivation, aggression, anxiety- and depression-like behaviors) were observed. 5-HT1A knock down resulted in higher frequencies of self-grooming and sleeping away from the nest, delayed retrieval of displaced pups back to the nest, and increased anxiety-like behavior. Overall, I found that female reproduction is associated with changes in serotonin receptor expression in numerous brain sites involved in postpartum behavior. Of particular interest, the normative change in 5-HT1A expression in the nucleus accumbens shell is altered in response to stress during pregnancy, and disrupting its expression reduces maternal motivation and increases postpartum anxiety-like behavior. Together, the results from this dissertation provide new insights into how the serotonergic system contributes to postpartum social and affective behaviors and offer a potential mechanism via the brain's reward system through which pharmacological treatments that affect the serotonin system (e.g., SSRIs) may work to alleviate postpartum affective disorders in women.
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