Dopaminergic inhibition of striatal cholinergic neurons: Synergistic blocking action of γ-butyrolactone and neuroleptic drugs

Summary

The effect of drugs administered i.v. on the release of acetylcholine (ACh) within the caudate nucleus perfused by means of push-pull cannulae was studied in the gallamine-immobilized cat. The antipsychotic compound clozapine (a dopamine receptor blocking agent) in a dose of 50 mg/kg markedly increased the ACh output; 20 mg/kg of the drug were ineffective. Combination of γ-butyrolactone with 20 mg/kg clozapine caused an increase of ACh output similar to that observed after 50 mg/kg clozapine. Similar results were obtained with chlorpromazine. This and other evidences suggest that cholinergic neurons in the striatum are under an inhibitory dopaminergic influence. The lack of effect on ACh output of relatively low doses of neuroleptics (e.g. 20 mg/kg clozapine) is probably explained by a partial dopamine receptor blockade which is surmounted by the feedback activation of dopaminergic neurons. Impairment of this activation by γ-butyrolactone is likely to result in a further diminution of dopamine at the receptors, leading to a disinhibition of cholinergic neurons.