Increase in the effectiveness of somatodendritic 5-HT-1A receptors in a rat model of tardive dyskinesia

Acta Neurobiol Exp (Wars). 2007;67(4):389-97. doi: 10.55782/ane-2007-1656.

Abstract

The present study concerns responsiveness of pre- and postsynaptic 5-hydroxytryptamine (5-HT)-1A receptors in a rat model of tardive dyskinesia (TD). Vacuous chewing movements (VCMs) in rats are widely accepted as an animal model of TD. Results show that haloperidol injected at a dose of 1 mg/kg twice a day for 5 weeks elicited VCMs, which increased in a time dependent manner following the drug administration for 3-5 weeks. Tolerance was produced in motor coordination during the potentiation of VCMs. Exploratory activity in an open field and in an activity box decreased in haloperidol treated animals. The effects of 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT; 0.5 mg/kg) were monitored 48-h after withdrawal from repeated administration of haloperidol. 8-OH-DPAT-induced locomotion was greater in haloperidol treated rats. 5-HT synthesis increased in haloperidol treated animals, while 8-OH-DPAT-induced decreases of 5-HT synthesis were greater in repeated haloperidol than repeated saline injected animals. The results suggest that an increase in the effectiveness of somatodendritic 5-HT-1A receptors may decrease the inhibitory influence of 5-HT on the activity of dopaminergic neurons to precipitate VCMs. The 5-HT-1A agonist may help to alleviate neuroleptic-induced TD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism*
  • Corpus Striatum / physiopathology
  • Disease Models, Animal
  • Dopamine Antagonists / toxicity
  • Dyskinesia, Drug-Induced / metabolism*
  • Haloperidol / toxicity
  • Male
  • Mastication / drug effects
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Serotonin / metabolism
  • Serotonin Receptor Agonists / pharmacology

Substances

  • Dopamine Antagonists
  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Haloperidol