Neuroanatomical basis of 5-HT1A receptor agonism in disruption of maternal behavior in rats

Abstract

The acute activation of serotonin 1 A (5-HT_1A) receptors appears to disrupt maternal behavior in rats; however, the underlying neuroanatomical mechanisms remain poorly understood. We employed two approaches to investigate the role of 5-HT_1A receptors in maternal behavior to address this knowledge gap. First, we used real-time polymerase chain reaction (PCR) to analyze 5-HT_1A receptor mRNA expression in female rats at different reproductive stages. We identified stage- and region-specific expression patterns, including temporary increases in the nucleus accumbens (NAc), ventral tegmental area (VTA), and dorsal raphe nucleus (DRN), as well as a temporary decrease in the medial prefrontal cortex (mPFC), amygdala, hippocampus, and ventromedial hypothalamic nucleus (VMH) during the perinatal, early, and middle postpartum periods. These findings suggest that coordinated 5-HT_1A activity across these brain regions is critical for normal maternal behavior. Second, we used c-Fos immunohistochemistry to elucidate the central mechanisms underlying the effects of the acute and repeated administration of 8-OH-DPAT (a 5-HT_1A receptor agonist, 1.0 mg/kg, sc.) on maternal behavior. Acute 8-OH-DPAT administration disrupted maternal behaviors, including pup retrieval, pup licking, nest building and hovering over pups, while simultaneously increased c-Fos expression in the mPFC, ventral bed nucleus of the stria terminalis (vBNST), NAc shell, lateral septum (LS), and medial amygdala (MeA). Disruptions in pup retrieval, pup licking and nest building persisted following five days of repeated 8-OH-DPAT treatment, whereas hovering over pups showed substantial recovery, returning to near-normal levels. Concurrently, c-Fos expression increased in the vBNST but decreased in the mPFC, MeA, and DRN. These results suggest that acute and repeated 8-OH-DPAT administration disrupts maternal behavior via distinct presynaptic and postsynaptic 5-HT_1A receptor mechanisms. This study highlights the complex regulatory role of 5-HT_1A receptor activity in maternal care and provides insights into the neuroanatomical and neurochemical mechanisms underlying maternal behavior.