Effects of early postnatal guanethidine administration on adrenal medulla and brain of developing rats

Abstract

Starting at 2 days of postnatal age, rats were injected with guanethidine (50 mg/kg, s.c.) once daily for 5 days and the adrenals were analyzed for catecholamines (CA), tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH); the brain was analyzed for TH and ornithine decarboxylase (ODC). Guanethidine treatment produced a 40–80 per cent increase in the adrenal CA, TH and DBH values, with return to normal by 3–4 weeks of age. Pretreatment of neonates with chlorisondamine (10 mg/kg, s.c.) prevented the stimulatory effects, indicating that guanethidine might act by direct nicotinic stimulation in neonates. In contrast, administration of guanethidine to adult rats had little or no effect on adrenal CA, TH or DBH, indicating that the stimulatory effect is unique to the developing animal. In the brain, administration of guanethidine resulted in an initial deficit and subsequent enhancement of ODC activity, suggesting a delay in cellular proliferation. TH activity was stimulated initially but was subnormal at later stages; the latter phenomenon may be related to incomplete function of the neonatal blood-brain barrier permitting a consequent central neurotoxic effect of guanethidine.