Tiagabine inhibits haloperidol-induced oral dyskinesias in rats

X. M. Gao, T. Kakigi, M. B. Friedman, C. A. Tamminga

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Chronic administration of haloperidol to male Sprague Dawley rats for 6 months at a dosage of 1.5 mg/kg/day produces oral dyskinesias in a significant percent of the treated group. This has been used as an animal model of tardive dyskinesia in several laboratories, because the rat movements display characteristics reminiscent of the human dyskinetic condition. Previously, we have reported a reduction in these haloperidol-induced oral dyskinesias with the coadministration of a direct acting GABA agonist progabide. Here, we have tested an indirect acting GABA agonist, tiagabine, coadministered with haloperidol, for its effect on the oral dyskinesias. At a dosage of 75 mg/kg/day tiagabine significantly inhibited the onset of vacuous chewing movements (VCMs), decreasing the average movement severity from 11.2 ± 2.0 to 4.4 ± 1.4, compared with a placebo rate of 1.3 ± 0.5 (VCMs/5 min). These data support the proposition that an effective, potent GABAmimetic coadministered with haloperidol, will block the onset of rat oral dyskinesias. This conclusion has important implications for the treatment and prevention of tardive dyskinesia in humans.

Original languageEnglish (US)
Pages (from-to)63-69
Number of pages7
JournalJournal of Neural Transmission
Volume95
Issue number1
DOIs
StatePublished - Feb 1 1994

Keywords

  • GABAmimetic
  • Tardive dyskinesia
  • haloperidol
  • tiagabine

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

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