TIAGABINE INHIBITS HALOPERIDOL-INDUCED ORAL DYSKINESIAS IN RATS

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 s ignificant percent of the treated group. This has been used as an anim al model of tardive dyskinesia in several laboratories, because the ra t movements display characteristics reminiscent of the human dyskineti c condition. Previously, we have reported a reduction in these haloper idol-induced oral dyskinesias with the coadministration of a direct ac ting GABA agonist progabide. Here, we have tested an indirect acting G ABA agonist, tiagabine, coadministered with haloperidol, for its effec t on the oral dyskinesias. At a dosage of 75 mg/kg/day tiagabine signi ficantly inhibited the onset of vacuous chewing movements (VCMs), decr easing 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 coadmini stered with haloperidol, will block the onset of rat oral dyskinesias. This conclusion has important implications for the treatment and prev ention of tardive dyskinesia in humans.