Possible mechanism of action in melatonin attenuation of haloperidol-induced orofacial dyskinesia.
Tardive dyskinesia (TD) is a late complication of prolonged neuroleptic treatment characterized by involuntary movements of the oral region. In spite of high incidence and much research, the pathophysiology of this devastating movement disorder remains elusive. Chronic treatment with neuroleptics leads to the development of abnormal oral movements in rats, referred to as vacuous chewing movements (VCMs). VCMs in rats are widely accepted as an animal model of TD. Rats chronically treated with haloperidol (1.5 mg/kg ip) significantly developed VCMs and tongue protrusions. Melatonin dose-dependently (1, 2, and 5 mg/kg) reversed the haloperidol-induced VCM and tongue protrusions frequencies. Biochemical analysis reveals that chronic haloperidol treatment significantly induced lipid peroxidation and decreased the forebrain glutathione (GSH) levels in the rats. Chronic haloperidol-treated rats also showed decreased levels of antioxidant defense enzymes, superoxide dismutase (SOD), and catalase. Coadministration of melatonin (1, 2, and 5 mg/kg) along with haloperidol significantly reduced the lipid peroxidation and restored the decreased GSH levels by chronic haloperidol treatment, and significantly reversed the haloperidol-induced decrease in forebrain SOD and catalase levels in rats. However, a lower dose of melatonin (1 mg/kg) failed to reverse chronic haloperidol-induced decreases in forebrain GSH, SOD, and catalase levels. In conclusion, melatonin could be screened as a potential drug candidate for the prevention or treatment of neuroleptic-induced orofacial dyskinesia.
Naidu
Pattipati S
PS
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, 160 014, Chandigarh, India.
Singh
Amanpreet
A
Kaur
Pushpinder
P
Sandhir
Rajat
R
Kulkarni
Shrinivas K
SK
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism / Q000517:prevention & control*; D005609:Free Radicals / Q000378:metabolism; D006220:Haloperidol / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005609:Free Radicals; D006220:Haloperidol; D008550:Melatonin