Behavioral effects of long-term neuroleptic treatment in Cebus monkeys.
Tardive dyskinesia (TD) occurs in predisposed individuals receiving neuroleptic treatment, but prior to the onset of symptoms it is not possible to predict who is at risk for this disorder. If the time course for evolving symptoms, perhaps mediated through dopamine hypersensitivity, could be identified, treatment interventions could be initiated. Eight male Cebus monkeys (15-18 years old) were tested with the dopamine agonists apomorphine, d-amphetamine, bromocriptine, and pergolide before, during, and after 3 months of treatment with haloperidol 0.25 mg/kg daily PO. This treatment cycle was repeated four times. Apomorphine and amphetamine produced moderate buccolinguo-masticatory (BLM) signs. Bromocriptine and pergolide produced very few BLMs. Initially haloperidol suppressed dopamine agonist-induced BLMs, but tolerance to the effect developed and was replaced by a potentiation of apomorphine-induced BLMs. Markedly increased apomorphine- and amphetamine-induced BLMs were seen following the first 3 months of haloperidol medication (behavioral hypersensitivity), but this gradually decreased to near-baseline levels, even with re-exposure to neuroleptics in the four treatment cycles. Bromocriptine and pergolide produced no signs of BLM behavioral hypersensitivity. These findings suggest that long-term neuroleptic treatment in nonhuman primates induces dynamic compensatory CNS changes, which may not fully explain the pathogenesis of TD on the basis of dopamine hypersensitivity.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001971:Bromocriptine / Q000494:pharmacology; D002428:Cebus; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004873:Ergolines / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D008409:Mastication / Q000187:drug effects; D010479:Pergolide; D011954:Receptors, Dopamine / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects
D004873:Ergolines; D011954:Receptors, Dopamine; D010479:Pergolide; D001971:Bromocriptine; D006220:Haloperidol; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine