The acetylcholine-dopamine balance in the basal ganglia of rhesus monkeys and its role in dynamic, dystonic, dyskinetic, and epileptoid motor activities

Summary

Behavioural analyses have been made of effects brought about by both single and combined injections of dopamine, haloperidol, carbachol and atropine into the caput nuclei caudati of rhesus monkeys. High doses of dopamine produced the subsequent development of three types of behavioural changes: an increase in the number of skilled manipulation movements (the dynamic phase); the appearance of a dystonic torticollis (the dystonic phase); and, finally, the appearance of an oro-lingual-facial dyskinesia and a number of dyskinetic activities in the extremities (the dyskinetic phase). Low doses of dopamine solely produced the dynamic phase. Haloperidol only inhibited the dopamine-induced dynamic and dystonic phase: it did not suppress the dyskinetic phase. High doses of carbachol produced the subsequent development of four phases: a dynamic, dystonic, dyskinetic and epileptoid phase. The last one was marked by the appearance of secondary generalized epileptic seizures. Low doses of carbachol solely produced the dynamic phase. Atropine inhibited the carbachol-induced dynamic, dystonic and epileptoid phase; it did not suppress the dyskinetic phase. High doses of dopamine strongly modified the carbachol-induced phases: dopamine intensified the dystonic phase on the one hand, but it abolished the generalized epileptic seizures on the other hand.

Apart from the fact that the data presented have confirmed that both dopaminergic and cholinergic mechanisms within the basal ganglia of rhesus monkeys are involved in the elicitation and modulation of both normal and abnormal motor activities, they have also revealed that the simple concept of a striatal acetylcholine-dopamine “see-saw” has to be revised. Furthermore, the data have suggested that development of supersensitive dopaminesensitive sites is not the only mechanism that underlies the elicitation of the oro-lingual-facial dyskinesia. And, finally, the present experiments have given clearcut evidence that an intrastriatal acetylcholine-dopamine “seesaw” fulfils an essential role in the process involved in the generalization of epileptic seizures.