Developmental regulation of 5-HT1A receptor mRNA in the fetal limbic system: response to antenatal glucocorticoid

The developmental changes in 5-HT1A receptor mRNA expression associated with advancing gestational age were examined in the fetal guinea pig hippocampus and dentate gyrus (DG) by in situ hybridization. We found that 5-HT1A receptor mRNA was present in the hippocampal CA1 subfield and dentate gyrus (DG), and was significantly (P < 0.05) elevated in the DG during the period of rapid brain growth [gestational day (gd) 50; term = 70 days]. Glucocorticoids have been shown to alter 5-HT1A receptor mRNA expression in the adult, but nothing is known about their impact on the developing fetal brain. Expression of 5-HT1A receptor mRNA in the fetal hippocampus was measured following repeated maternal administration (gd40, 41, 50, 51, 60 and 61) of synthetic glucocorticoid (dexamethasone; 1 and 10 mg/kg). Levels of 5-HT1A receptor mRNA were significantly (P < 0.005) elevated in CA1 and DG following repeated exposure to high-dose glucocorticoid (10 mg/kg) in male, but not in female fetuses. Because fetal exposure to glucocorticoids programs hypothalamo-pituitary-adrenal (HPA) function, and hippocampal serotonin is known to influence glucocorticoid receptor (GR) expression, the glucocorticoid-mediated changes in 5-HT1A receptor mRNA may play a role in the programming of HPA function.