Tardive dyskinesia model in the common marmoset.
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.
Klintenberg
Rebecka
R
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Gunne
Lars
L
Andrén
Per E
PE
D000818:Animals; D001712:Biperiden / Q000633:toxicity*; D002144:Callithrix; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D004409:Dyskinesia, Drug-Induced / Q000175:diagnosis; D005260:Female; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000633:toxicity*; D008297:Male; D009460:Neurologic Examination / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000175:diagnosis
D001712:Biperiden; C033563:haloperidol decanoate; D006220:Haloperidol