Possible involvement of prostaglandins in haloperidol-induced orofacial dyskinesia in rats.
Dopaminergic abnormality is one of the pathological mechanisms involved in the pathophysiology of tardive dyskinesia, a late complication of neuroleptic treatment. Prostaglandins modulate the dopamine release in the striatum, the principle area involved in the pathophysiology of tardive dyskinesia. Rats were chronically treated with haloperidol (HPD) (1.5 mg/kg) for a period of 21 days, to induce orofacial dyskinesia. Behavioural assessment of orofacial dyskinesia was done 24 h after the last dose of haloperidol. Catalepsy was induced in rats by acute treatment with haloperidol (1 mg/kg), and catalepsy was scored for the next 4 h. Chronic haloperidol treatment induced profound vacuous chewing movements in rats. Indomethacin, a nonselective cyclooxygenase inhibitor dose-dependently (5-20 mg/kg) suppressed the vacuous chewing movements count in haloperidol-treated animals. In conclusion, the results of the present study infer that prostaglandins might play a significant role in the haloperidol-induced vacuous chewing movements, and prostaglandin synthesis inhibitors can serve as novel drug candidates for the treatment of tardive dyskinesia.
Naidu
P S
PS
Division of Pharmacology, University Institute of Pharmaceutical Sciences, Panjab University, -160014, Chandigarh, India.
Kulkarni
S K
SK
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D005152:Facial Muscles / Q000187:drug effects; D006220:Haloperidol / Q000008:administration & dosage*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D006220:Haloperidol; D007213:Indomethacin