Effects of prenatal reserpine administration on development of the rat adrenal medulla and central nervous system.

Reserpine (1 mg/kg s.c.) was administered to pregnant rats at different periods of gestation. Rats born to mothers who received reserpine on days 6, 5 and 4 or 4, 3 and 2 before delivery showed early postnatal adrenal catecholamine depletion, an effect which can be attributed to a direct action of the drug; however, at no time was induction of tyrosine hydroxylase or dopamine beta-hydroxylase observed. Administration of reserpine on days 9, 8 and 7 before delivery did not alter postnatal adrenal catecholamine levels in the offspring but produced permanent elevations in enzyme activities and vesicular amine uptake beginning at 10 days of age. Studies utilizing direct stimulation with nicotine indicated that the inherent responsiveness of the adrenal medulla itself was the same in control and reserpine-exposed pups. These data all suggest that sympathoadrenal tone has been permanently increased in the offspring of rats which have been exposed to reserpine early in gestation. In the brain, administration of reserpine on days 6, 5 and 4 before delivery resulted in a delay in early postnatal development of brain weight and synaptosomal uptake mechanisms, and at later stages subnormal tyrosine hydroxylase activities. When reserpine was given on days 9, 8 and 7 before delivery, only the deficiency in tyrosine hydroxylase was seen. These studies indicate that long-lasting changes in both peripheral and central nervous system catecholamine disposition can be produced by prenatal reserpine administration.

Duke Scholars

Author Frederic J. Seidler Pharmacology & Cancer Biology

Author Theodore Alan Slotkin Pharmacology & Cancer Biology