Ontogenesis of neostriatal cholinergic neurones in the rat and development of their sensitivity to neuroleptic drugs.

Simultaneous determinations of the striatal contents in acetylcholine (ACh), choline acetyl-transferase (ChAc) and acetyl-cholinesterase (AChE) were made in neonate rats from day 4 to day 16 after birth. While, during this period, ChAc and AChE increased 14 and 5-fold, respectively, the change of ACh levels was smaller and more gradual. ACh levels were unaltered following the injection of thioproperazine (5 mg/kg) until day 8, then within 6 days the cholinergic neurones developed a full sensitivity to this drug. The sensitivity to haloperidol (4 mg/kg), pimozide (4 mg/kg) and to the dopamine receptor stimulating drug apomorphine (10 mg/kg) appeared along with that to thioproperazine. These data confirm and extend previous reports that rat striatal cholinergic neurones are immature at birth; they suggest, in addition, that the development of dopamine receptors occurs prior to the appearance of functional cholinergic synapses or concomitant with this event.