Reversal of neuroleptic-induced orofacial dyskinesia by 5-HT3 receptor antagonists

Eur J Pharmacol. 2001 May 25;420(2-3):113-7. doi: 10.1016/s0014-2999(01)00986-4.


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.

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Dose-Response Relationship, Drug
  • Dyskinesia, Drug-Induced / etiology
  • Dyskinesia, Drug-Induced / prevention & control*
  • Haloperidol / pharmacology
  • Indoles / pharmacology
  • Male
  • Ondansetron / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists / pharmacology*
  • Tropisetron


  • Antipsychotic Agents
  • Indoles
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • Ondansetron
  • Tropisetron
  • Haloperidol