Progressive changes in the acute dyskinetic syndrome as a function of repeated elicitation in squirrel monkeys.
Various neuroleptic-induced motor disorders that appear in primates previously treated with neuroleptics are collectively designated the acute dyskinetic syndrome. The relative incidence of these motor disorders was examined as the syndrome was repeatedly elicited by haloperidol and other dopamine antagonists in individual monkeys. After several weekly or biweekly treatments with haloperidol (1.25 mg/kg orally), catalepsy began to appear, which was then accompanied by athetoid movements (writhing and limb extensions) as intermittent neuroleptic treatment continued. Other dyskinetic movements ('duck walk', oral dyskinesias, pushing of the head into a cage corner, and perseverative circling) that were suggestive of hyperkinesia subsequently began to be elicited by haloperidol and other neuroleptics after additional treatments with these drugs had intervened. As intermittent treatments continued, tolerance to the athetoid movements gradually developed and, eventually, only circling and pushing could be consistently elicited by haloperidol. In monkeys that had reached this phase, the athetoid movements were not again induced by higher doses of haloperidol (up to 5 mg/kg), chlorpromazine (3 mg/kg), or metoclopramide (3 mg/kg). In these tolerant monkeys, haloperidol impaired Sidman avoidance performance less and benztropine more than in drug-naive monkeys. Neither pharmacokinetic changes nor behavioral tolerance could readily account for these results. It is hypothesized that they reflect progressive functional alterations in dopaminergic or cholinergic neurotransmission.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000502:physiology*; D001590:Benztropine / Q000494:pharmacology; D004361:Drug Tolerance; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009069:Movement Disorders / Q000503:physiopathology*; D012453:Saimiri
D014150:Antipsychotic Agents; D001590:Benztropine; D006220:Haloperidol