Methylphenidate, apomorphine, THIP, and diazepam in monkeys: dopamine-GABA behavior related to psychoses and tardive dyskinesia.
In eight monkeys (Cercopithecus aethiops), previously treated with haloperidol for 4-14 months, we have examined the behavioral effect of: (1) methylphenidate vs apomorphine; (2) 4,5,6,7-tetrahydroisoxazolo-(5,4-c)-pyridin-3-ol(THIP, a GABA agonist) vs diazepam; and (3) THIP and diazepam in methylphenidate-induced behavior. Methylphenidate (0.5-5.0 mg/kg) and apomorphine (0.1-0.5 mg/kg) both increased locomotion, but otherwise exhibited different behavioral profiles. Methylphenidate induced repetitive movements of head, limbs, and trunk, and hallucinatory-like behavior, but not oral hyperkinesia (licking and gnawing), whereas apomorphine preferentially caused oral hyperkinesia. THIP produced a syndrome of bradykinesia, dystonia, ataxia, myoclonus, sedation, and decreased responsiveness, whereas diazepam produced only bradykinesia, ataxia, sedation, and decreased responsiveness, but not dystonia and myoclonus. Methylphenidate-induced locomotion and repetitive movements were reduced by THIP and diazepam, whereas hallucinatory-like behavior was markedly aggravated by THIP, but not by diazepam.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D003975:Diazepam / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D004347:Drug Interactions; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D005260:Female; D006212:Hallucinations / Q000139:chemically induced; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D010080:Oxazoles / Q000494:pharmacology*; D011605:Psychoses, Substance-Induced / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D007555:Isoxazoles; D010080:Oxazoles; D008774:Methylphenidate; D005680:gamma-Aminobutyric Acid; C015542:gaboxadol; D001058:Apomorphine; D003975:Diazepam; D004298:Dopamine