Journal
MOVEMENT DISORDERS
Volume 17, Issue 2, Pages 360-365Publisher
WILEY
DOI: 10.1002/mds.10070
Keywords
tardive dyskinesia; marmosets; acute dystonia; haloperidol; animal model; nonhuman primate
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Thirteen adult common marmosets (Callithrix jacchus) were given once-monthly injections of haloperidol decanoate (5-15 mg/kg i.m.) for one year. Thereafter, drug-free and treatment periods alternated at 3-month intervals. After 2.5 to 14 months, 12 monkeys showed symptoms of tardive dyskinesia (TD), such as periocular and perioral twitchings, tongue protrusions, masticatory movements, and choreic movements in arms and legs. When TD symptoms were evident, the periodic treatment was interrupted and symptoms persisted for at least 5 months after the last haloperidol dose, worsened by injection of the anticholinergic drug biperiden. An injection of nondepot haloperidol (0.12 or 0.25 mg/kg) produced a reduction of TD symptoms. At the end of the study, nondepot haloperidol was injected once a week at two doses (0.12 and 0.25 mg/kg i.m.). A syndrome of excitation with peculiar behavior, interpreted as acute dystonia, was precipitated in all animals. The animals showed sustained retrocollis, climbing upside down, biting the perch, repetitive turnings, and frequent backward movements. The dystonic movements lasted approximately 6 hours and were reduced but not completely extinguished by biperiden (0.1 mg/kg). The TD syndrome registered in marmosets may provide a useful model for screening new antipsychotics for their propensity to induce TD. (C) 2002 Movement Disorder Society.
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