High frequency stimulation and temporary inactivation of the subthalamic nucleus reduce quinpirole-induced compulsive checking behavior in rats

Obsessive-compulsive disorder (OCD) represents a highly prevalent and impairing psychiatric disorder. Functional and structural imaging studies implicate the involvement of basal ganglia-thalamo-cortical circuits in the pathophysiology of this disorder. In patients remaining resistant to pharmaco- and behavioral therapy, modulation of these circuits may consequently reverse clinical symptoms. High frequency stimulation (HFS) of the subthalamic nucleus (STN), an important station of the basal ganglia-thalamo-cortical circuits, has been reported to reduce obsessive-compulsive symptoms in a few Parkinson's disease patients with comorbid OCD. The present study tested the effects of bilateral HFS of the STN and of bilateral pharmacological inactivation of the STN (via intracranial administration of the GABA agonist muscimol) on checking behavior in the quinpirole rat model of OCD. We demonstrate that both HFS and pharmacological inactivation of the STN reduce quinpirole-induced compulsive checking behavior. We conclude that functional inhibition of the STN can alleviate compulsive checking, and suggest the STN as a potential target structure for HFS in the treatment of OCD. (C) 2007 Elsevier Inc. All rights reserved.