Critical periods for effects of prenatal reserpine administration on development of rat brain and adrenal medulla

Abstract

The specific prenatal time periods of drug exposure required for developmental alterations produced by maternal reserpine administration were examined by studying catecholamine systems in brain and adrenal medulla. Reserpine (1 mg/kg s.c.) was administered to three groups of pregnant rats on 6, 7 and 8 days of gestation (group I), 9, 10 and 11 days (group II), or 12, 13 and 14 days (group III); there was maternal weight loss and a slight reduction in litter size in all three groups. Offspring in groups I and II exhibited only a few neurochemical developmental alterations and these were of short duration ; however these groups demonstrated greater effects on body weight gain. Rats in group III showed marked increases in adrenal tyrosine hydroxylase and dopamine β-hydroxylase activities beginning at about two weeks of age and persisting into young adulthood. Brain tyrosine hydroxylase development was delayed in all three groups, but again only group III showed a persistent effect. Measurements of ornithine decarboxylase (ODC) activity, a more general marker for cellular and metabolic development, also indicated that brain development was most affected in group III: the ODC changes preceded those in neurotransmitter enzymes. These studies demonstrate the existence of a critical period for actions of maternally-administered reserpine on developing brain and adrenal medulla, involving enzymes specific to catecholaminergic systems and the polyamine system.