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.