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

Creed, Meaghan; Hamani, Clement; Nobrega, José N.

doi:10.1016/j.euroneuro.2010.06.012

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Volume 21, Issue 5 , Pages 393-400, May 2011

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

Meaghan Creed
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
- Neuroimaging Research Section, Centre for Addiction and Mental Health, Toronto, ON, Canada
Clement Hamani
- Neuroimaging Research Section, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Division of Neurosurgery, Toronto Western Hospital, Toronto, ON, Canada
José N. Nobrega
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Department of Psychology, University of Toronto, Toronto, ON, Canada
- Neuroimaging Research Section, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Corresponding author. Neuroimaging Research Section, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada M5T 1R8. Tel.: +1 416 535 8501x6259; fax: +1 416 979 4739.

Received 11 February 2010; received in revised form 15 June 2010; accepted 23 June 2010. published online 12 July 2010.

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 (100μA) acutely to the entopeduncular nucleus (EPN) or subthalamic nucleus (STN) in rats with well established vacuous chewing movements (VCMs) induced by 12weeks of haloperidol (HAL) treatment. Stimulation of the STN or EPN resulted in significant reductions in VCM counts at frequencies of 30, 60 or 130Hz. In the STN DBS groups, effects were significantly more pronounced at 130Hz than at lower frequencies, whereas at the EPN the three frequencies were equipotent. Unilateral stimulation at 130Hz 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.