Effects of subthalamic nucleus lesions in a putative model of tardive dyskinesia in the rat.

The effects of bilateral excitotoxic lesions of the subthalamic nucleus on vacuous chewing movements induced by chronic neuroleptic therapy were examined in the rat. Fluphenazine decanoate (25 mg/kg i.m.q 3 weeks x 24 weeks) induced vacuous chewing movements, as previously described. This response was suppressed to control levels in animals tested 1-3 weeks following bilateral infusion of quinolinic acid (100 nmol/1 microliter per side) into the subthalamic nucleus. Subthalamic nucleus lesions resulted in increased locomotion and sniffing in neuroleptic-naive animals, but these responses were suppressed by concomitant neuroleptic treatment. As vacuous chewing movements induced by chronic neuroleptics are considered to be analogous to tardive dyskinesia in humans, our findings lend further support to the importance of the subthalamic nucleus in the regulation of orofacial movements and suggest that tardive dyskinesia may, in part, be related to altered activity in this structure. This, in turn, suggests that current models of basal ganglia function are inadequate to account for certain pathological states and require re-examination.