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.