Effect of Prenatal Stress and Serotonin Depletion on Postnatal Serotonin Metabolism in Wistar Rats

Abstract

Prenatal stress in rats results in structural, physiological and behavioral alterations that persist in adulthood. Serotonin (5-HT) is an important neurotransmitter known to be involved in these prenatal stressinduced behavioral alterations. The aim of the study was to investigate the effects of interrupted synthesis of 5-HT and immobilization stress during different gestational period on brain serotonergic system of male and female neonatal (postnatal day 15) and adult rats (60 days old). Pregnant rats were subjected to restraint stress three times daily for 45 min during day 3-14 (G 3-14) or day 14-21 (G 14-21) of pregnancy. Another group of pregnant rats were injected with the inhibitor of 5-HT synthesis, parachlorophenylalanine (p-CPA, 400 mg/kg/2ml, single dose, ip) on day 9 or 17 of pregnancy. Following sacrifice, tissue concentrations of 5-HT and its metabolite 5-hydroxy indole acetic acid (5-HIAA) were analyzed in whole brains of neonatal pups and in brainstem, hypothalamus, hippocampus, and frontal cortex of adults. Stress during G 14-21 days showed a significant reduction of 5-HT and 5-HIAA levels in early neonatal development but not later during adulthood. Decreases in whole brain concentrations of 5-HT and 5-HIAA were observed in p-CPA 9 and G 14-21 neonatal pups. The concentration of 5-HT was decreased in frontal cortex and hypothalamus of adult rats receiving p-CPA. Prenatal stress affects tissue concentrations of 5-HT and 5-HIAA in neonatal pups and adults and it is possible that such changes may underlie the reported behavioral deficits in offspring of stressed female rats. These data also provide evidence that the critical period for prenatal stress-induced changes in brain 5-HT neurons were between days 14-21 (during final trimester of pregnancy).