Tardive dyskinesia (TD) is a motor disorder of the orofacial region resulting from chronic
neuroleptic treatment. A high incidence and irreversibility of this hyperkinetic disorder has been considered a major clinical issue in the treatment of
schizophrenia. The molecular mechanism related to the pathophysiology of
tardive dyskinesia is not completely known. Various animal studies have demonstrated an enhanced oxidative stress and increased glutamatergic transmission as well as inhibition in the
glutamate uptake after the chronic administration of
haloperidol. The present study investigated the effect of
curcumin, an
antioxidant, in
haloperidol-induced
tardive dyskinesia by using different behavioural (orofacial dyskinetic movements, stereotypy, locomotor activity, % retention), biochemical (lipid peroxidation,
reduced glutathione levels,
antioxidant enzyme levels (SOD and
catalase) and neurochemical (
neurotransmitter levels) parameters. Chronic administration of
haloperidol (1 mg/kg i.p. for 21 days) significantly increased vacuous chewing movements (VCM's), tongue protrusions, facial jerking in rats which was dose-dependently inhibited by
curcumin. Chronic administration of
haloperidol also resulted in increased
dopamine receptor sensitivity as evident by increased locomotor activity and stereotypy and also decreased % retention time on elevated plus maze paradigm. Pretreatment with
curcumin reversed these behavioral changes. Besides,
haloperidol also induced oxidative damage in all major regions of brain which was attenuated by
curcumin, especially in the subcortical region containing striatum. On chronic administration of
haloperidol, there was a decrease in turnover of
dopamine,
serotonin and
norepinephrine in both cortical and subcortical regions which was again dose-dependently reversed by treatment with
curcumin. The findings of the present study suggested for the involvement of
free radicals in the development of
neuroleptic-induced
tardive dyskinesia and point to
curcumin as a possible therapeutic option to treat this
hyperkinetic movement disorder.