OCIMUM SANCTUM Linn. ATTENUATES HALOPERIDOL INDUCED TARDIVE DYSKINESIA AND ASSOCIATED BEHAVIOURAL, BIOCHEMICAL AND NEUROCHEMICAL CHANGES IN RATS

Abstract:

The present study investigated the effect of Ocimum sanctum, an antioxidant, in haloperidol-induced tardive dyskinesia, biochemical (lipid peroxidation, reduced glutathione levels, antioxidant enzyme level (catalase) and neurochemical (neurotransmitter levels) parameters. Tardive dyskinesia is a complex hyperkinetic syndrome consisting of choriform, athetoid or rhythmically abnormal involuntary movements. The irreversibility of this hyperkinetic disorder has been considered a major clinical issue in the treatment of schizophrenia. The pathophysiology of tardive dyskinesia is not completely known. Numerous studies showed that an enhanced oxidative stress and increased glutamatergic transmission as well as inhibition in the glutamate uptake after the chronic administration of haloperidol are the cause for tardive dyskinesia. Haloperidol is a widely used neuroleptic drug for the treatment of acute and chronic psychosis. The use of haloperidol is limited by extrapyramidal movement disorders. Chronic administration of haloperidol (1 mg/kg i.p. for 21 days) significantly increased vacuous chewing movements (VCM's in rats which was dose-dependently inhibited by Ocimum sanctum. Pretreatment with Ocimum sanctum reversed these behavioral changes. Besides, haloperidol also induced oxidative damage in brain which was attenuated by Ocimum sanctum. On chronic administration of haloperidol, there was a decrease in turnover of dopamine, GABA and norepinephrine in the brain which was again dose-dependently reversed by treatment with Ocimum sanctum.  The results of the present study suggested there is involvement of free radicals in the development of neuroleptic-induced tardive dyskinesia and Ocimum sanctum as a possible therapeutic potential to treat this disorder.

Key Words: Tardive dyskinesia, Haloperidol, Ocimum sanctum.