The traditional neuroleptic drugs are chronically used in the treatment ,pf schizophrenia am) other psychotic disorders. A serious side effect of long term use of traditional neuroleplics is the precipitation of tardive dyskinesia (TD). Characterized involuntary movements of the face and extremities. Vacuous chewing movements (VCMS) in animals following tong term administration of haloperidol is often taken as a model of TD. Dopamine (DA) D2 receptors in the striatum are involved in the control of motor activity. While serotonin (5-hydroxy tryptamine: 5-HT) elicits an inhibitory influence on the activity of dopaminergic neurons Previous studies from our laboratory show that the inhibitory influence of 5-UT on. The activity of doparninergic neurons is decreased following long term administration of haloperidol. This is because of the supersensitization of somatodendritic 5-HT-I A receptors. The inhibitory effects of S.HT on the activity of dopaminergic neurons are mediated via 5-HT-2C receptors located on the cell body and nerve terminal ends of doparninergic neurons. The present study therefore concerns neurochemical effects of 5-l-I’T SD receptor agonist, 1(m-ChlorophenyI) piperazinc (rn-UP) in the striatum of rats repeatedly treated with haloperidol and exhibiting orofacial dyskinesia. Results show that haloperidol injected at a dose of I mg/ kg twice a day for two weeks elicited VCMs, which increased in time dependent manner following the drug administration for 5 weeks. The neurochemical effects of m-CPP were monitored 48-h after the drug withdrawal. Administration of haloperidol increased SHT and DA metabolism in the striatum. Administration of m-CPP increased 5-FIT metabolism and decreased DA metabolism in repeated saline treated animals not exhibiting VCMs. Conversely, administration of m-CPP resulted in a decrease of 5-HT metabolism in repeated haloperidol treated animals exhibiting VCMs. m-CPP4nducbd decreases of DA metabolism were also greater in repeated haloperidol treated animals. The results suggest that a decrease in the responsiveness of 5HT_2C receptors and an increase in the responsiveness of dopamine 02 receptors are involved in the precipitation of TD.
D J HALEEM ,N SAMAD ,M A HALEEM ,
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