Deep brain stimulation of the subthalamic or entopeduncular nucleus attenuates vacuous chewing movements in a rodent model of tardive dyskinesia

Abstract

Deep brain stimulation (DBS) has recently emerged as a potential intervention for treatment-resistant tardive dyskinesia (TD). Despite promising case reports, no consensus exists as yet regarding optimal stimulation parameters or neuroanatomical target for DBS in TD. Here we report the use of DBS in an animal model of TD. We applied DBS (100 μA) acutely to the entopeduncular nucleus (EPN) or subthalamic nucleus (STN) in rats with well established vacuous chewing movements (VCMs) induced by 12 weeks of haloperidol (HAL) treatment. Stimulation of the STN or EPN resulted in significant reductions in VCM counts at frequencies of 30, 60 or 130 Hz. In the STN DBS groups, effects were significantly more pronounced at 130 Hz than at lower frequencies, whereas at the EPN the three frequencies were equipotent. Unilateral stimulation at 130 Hz was also effective when applied to either nucleus. These results suggest that stimulation of either the EPN or STN significantly alleviates oral dyskinesias induced by chronic HAL. The chronic HAL VCM model preparation may be useful to explore mechanisms underlying DBS effects in drug-induced dyskinesias.