Effects of Combined Therapy with Nifedipine and Melatonin on Haloperidol- Induced Tardive Dyskinesia in Rats

Tardive Dyskinesia (TD) is a severe movement disorder of the orofacial region caused by the typical neuroleptic, haloperidol. It was reported that haloperidol-induced TD is mediated through oxidative stress mechanism which is triggered by calcium overload. Moreover, the disturbance of melatonin secretion due to pineal gland calcification is linked to the pathophysiology of TD. Therefore, the aim of this study was to investigate the effect of combined therapy with nifedipine, a calcium channel blocker and melatonin, the powerful antioxidant on haloperidol-induced TD. Five groups of rats were treated as follow: Group1 and 2 were treated with vehicle and haloperidol, (1mg/kg, ip) respectively. Groups 3-5 were treated with nifedipine (20 mg/kg, orally), melatonin (5mg/kg, orally), nifedipine plus melatonin respectively then challenged with haloperidol for 21 days. Our results show that, haloperidol produced behavioral abnormalities and alterations in oxidative stress parameters. Interestingly, combined administration of nifedipine plus melatonin significantly reduced vacuous chewing movements (VCMs) and tongue protrusions frequency (TPF). Moreover, administration of both drugs improved oxidative stress parameters such as glutathione (GSH), lipid peroxide malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT) activities that were altered by haloperidol more than each drug alone. These results indicate that the deleterious effect of haloperidol in rat brain is at least in part due to oxidative stress and that co-administration of nifedipine plus melatonin may have neuroprotective effects related to antioxidant mechanisms.