Reversal of neuroleptic-induced orofacial dyskinesia by 5-HT3 receptor antagonists.
Tardive dyskinesia, a syndrome of abnormal, involuntary hyperkinetic movements that occurs during long-term neuroleptic therapy is a major limitation of chronic neuroleptic therapy. The pathophysiology of tardive dyskinesia is still an enigma. The objective of the present study was to elucidate the role of 5-HT3 receptor involvement in neuroleptic-induced vacuous chewing movements in rats. Rats chronically (for 21 days) treated with haloperidol (1.5 mg/kg, i.p.) significantly developed vacuous chewing movements, as compared to vehicle-treated controls. Both ondansetron and tropisetron dose-dependently (0.25, 0.5 and 1.0 mg/kg, i.p.) reversed the haloperidol-induced vacuous chewing movements. Serotonin acting through 5-HT3 receptors might play a significant role in the pathophysiology of tardive dyskinesia, and 5-HT3 receptor ligands can be exploited as novel therapeutic agents for the treatment of tardive dyskinesia.
Naidu
P S
PS
University Institute of Pharmaceutical Sciences, Panjab University, -160014, Chandigarh, India.
Kulkarni
S K
SK
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000517:prevention & control*; D006220:Haloperidol / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology*; D000077526:Tropisetron
D014150:Antipsychotic Agents; D007211:Indoles; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017294:Ondansetron; D000077526:Tropisetron; D006220:Haloperidol