Cholinergic modulation of stimulant-induced behavior

Stimulant-induced stereotypy, presumably mediated by nigrostriatal dopaminergic neurons, can be altered by the administration of cholinergic agonists or antagonists. Cholinergic, striatal interneurons have been postulated as the site of these effects, although the specific site of interaction between cholinergic and dopaminergic systems is unknown. The study reported here examined the effects of the cholinesterase inhibitor physostigmine, and several other cholinergic and anticholinergic drugs, on stimulant-induced behavior. Stereotypy was inhibited by physostigmine to the same degree whether induced by direct (apomorphine) or by indirect acting (amphetamine and methylphenidate) stimulants. The results are interpreted as indicating that the site of cholinergic modulation of stimulant-induced stereotypy is postsynaptic to the dopaminergic neurons which mediate stereotypy.