tropisetron and Dyskinesia--Drug-Induced

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.

Topics: Animals; Antipsychotic Agents; Behavior, Animal; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Haloperidol; Indoles; Male; Ondansetron; Rats; Rats, Wistar; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Serotonin Antagonists; Tropisetron