ONTOGENESIS OF DOPAMINERGIC-CHOLINERGIC INTERACTIONS IN THE RAT STRIATUM: A NEUROCHEMICAL STUDY

Abstract— In the striatum of the newborn rat, the activity of tyrosine hydroxylase, the concentration of dopamine and the activity of the synaptosomal high-affinity uptake process for dopamine is 10% of that of the adult; there is a linear and closely associated increase in all three parameters during maturation, achieving 75% of adult levels by 4 weeks after birth. In contrast, the specific activity of choline acetyltransferase exhibits a more delayed developmental rise commencing 1 week after birth; the concentration of acetylcholine is disproportionately high in the neonatal striatum and precedes the developmental increase in the activity of choline acetyltransferase. At birth, the specific activity of dopamine-sensitive adenylate cyclase is 20% of that of the adult striatum and achieves adult activity by 4 weeks after birth. Pretreatment with the neuroleptic, fluphenazinc. does not reduce the striatal content of acetylcholine until 8 days after birth. It is postulated that dopaminergic influences on cholinergic neuronal activity appear when the cholinergic neurons in the striatum cease dividing and start differentiating.