Pharmacological modification of experimental tardive dyskinesia.
Cebus apella monkeys subjected to chronic haloperidol administration develop neurologic disturbances very similar to neuroleptic-induced acute dystonia human beings. After varying lengths of time, certain monkeys develop a prolonged dyskinetic syndrome resembling tardive dyskinesia (TD), as seen clinically. Two monkeys with signs of TD were given single intramuscular injections of various compounds with known effects on the catecholaminergic, cholinergic, serotoninergic and GABA-ergic neurotransmittor systems, and their effect on the TD signs were rated. Dopamine receptor blockers as well as cholinergics had an ameliorating effect on the symptoms. Some compounds known to activate the GABA system, including some benzodiazepines and the GABA-transaminase inhibitor amino-oxyacetic acid, also reduced the symptoms, as did the serotonin precursor L-5HTP. Results with serotonin antagonists were equivocal. It is concluded that dopamine receptor blockade, as well as increased activity within the GABA-ergic or cholinergic systems cause alleviation of TD. The findings are in agreement with earlier reports in man and thus seem to validate this primate model.
D000818:Animals; D001921:Brain / Q000187:drug effects*; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D006220:Haloperidol; D000882:Haplorhini; D011950:Receptors, Cholinergic / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects
D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D006220:Haloperidol