Morin Attenuates Haloperidol Induced Tardive Dyskinesia and Oxidative Stress in Mice

Abstract

Antipsychotic treatment with classical neuroleptics in humans can produce a serious side effect, known as tardive dyskinesia (TD). TD, is most serious iatrogenic movement disorder, has been tentatively associated with nigrostriatal dopaminergic supersensitivity and with oxidative stress in brain region and the complete pathophysiology is still obscure. In the present study we investigated the effects of co-administration of morin (30 mg/kg b.w, for 14 days) and haloperidol (HP) (1.0 mg/kg i.p, once daily, for 14 days), as well as the effects of 14 days treatment with this dose of morin after withdrawal from HP in mice. Administration of HP led to significantly increased oxidative stress, reduced antioxidants, dopamine level and condensed behavior patterns (vacuous chewing movements (VCMs), narrow beam walking, akinesia, hang test and stride length measurement), reduced nigrostriatal dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT 2) and increase the inflammatory marker ?-actin  expressions. Pre-treatment with morin significantly reduces oxidative stress, improves dopamine level, ameliorate motor behavior and reversed expression of DAT, VMAT 2 and ?-actin in striatum. These results indicate that morin have bene?cial role in mitigating HP-induced damage of dopaminergic neurons, possibly via its neuroprotective and its antioxidant potential.

Key words: tardive dyskinesia, iatrogenic, bradykinesia, nigrostriatal, antioxidant