Effects of chronic haloperidol and clozapine on vacuous chewing and dopamine-mediated jaw movements in rats: evaluation of a revised animal model of tardive dyskinesia

Summary.

Rats received haloperidol (1.0 mg/kg i.p.) or clozapine (10 mg/kg i.p.), twice daily for 4 weeks: vacuous chewing -recorded 26 h after the final injection- similarly increased in both groups. Three h later, the rats were challenged with dopaminomimetics, and automatically recorded jaw movements were analysed. Both apomorphine and a mixture of D₁ and D₂ receptor agonists (SKF 38393 resp. quinpirole) increased jaw movements in haloperidol-treated, but not clozapine-treated rats; SKF 38393 or quinpirole remained ineffective, when given alone. A fixed dose of quinpirole together with increasing doses of SKF 38393, but not a fixed dose of SKF 38393 together with increasing doses of quinpirole, produced a dose-dependent increase in jaw movements in otherwise non-treated rats, suggesting that the noted haloperidol-induced increase was due to a shift in the D₁–D₂ receptor balance towards a predominance of D₁ receptors. This study presents a new animal model of tardive dyskinesia with predictive validity, good reliability and, especially, great efficiency.