Abstract
Tardive dyskinesia is a serious motor disorder of the orofacial region, resulting from chronic neuroleptic treatment of schizophrenia. Candesartan (AT1 antagonist) and lisinopril (ACE inhibitor) has been reported to possess antioxidant and neuroprotective effects. The present study is designed to investigate the effect of candesartan and lisinopril on haloperidol-induced orofacial dyskinesia and oxidative damage in rats. Tardive dyskinesia was induced by administering haloperidol (1 mg/kg i.p.) and concomitantly treated with candesartan (3 and 5 mg/kg p.o.) and lisinopril (10 and 15 mg/kg p.o.) for 3 weeks in male Wistar rats. Various behavioral parameters were assessed on days 0, 7, 14 and 21 and biochemical parameters were estimated at day 22. Chronic administration of haloperidol significantly increased stereotypic behaviors in rats, which were significantly improved by administration of candesartan and lisinopril. Chronic administration of haloperidol significantly increased oxidative stress and neuro-inflammation in the striatum region of the rat's brain. Co-administration of candesartan and lisinopril significantly attenuated the oxidative damage and neuro-inflammation in the haloperidol-treated rat. The present study supports the therapeutic use of candesartan and lisinopril in the treatment of typical antipsychotic-induced orofacial dyskinesia and possible antioxidant and neuro-inflammatory mechanisms.
Highlights
Tardive dyskinesia is a serious motor disorder of the orofacial region, resulting from chronic neuroleptic treatment of schizophrenia
Haloperidol is an antipsychotic drug used for the treatment of schizophrenia and is used frequently in animal models to study the pathogenesis of Tardive dyskinesia (TD).[2,3]
Chronic administration of haloperidol resulted in timedependent increases in vacuous chewing movements (VCMs), tongue protrusion and facial jerking in rats
Summary
Tardive dyskinesia is a serious motor disorder of the orofacial region, resulting from chronic neuroleptic treatment of schizophrenia. Tardive dyskinesia (TD) is a disabling and potentially irreversible motor complication encompassing all persistent, abnormal, involuntary hyperkinetic movements occurring in the setting of chronic therapy with dopamine receptorblocking agents, such as antipsychotic drugs.[1,2] Various theories have been put forward to understand the neuropathology of TD Some of these include dopaminergic hypersensitivity, disturbed balance between dopamine and cholinergic systems, dysfunctions of striatonigral GABAergic neurons and excitotoxicity.[3] the symptoms persist even after the withdrawal of typical antipsychotic drugs, indicating that these drugs produce some long term alterations in brain tasks that are no longer associated with drug usage.[4]. The pathophysiological mechanism of haloperidol-induced TD is still not clear
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