Modulation of subthalamic nucleus activity differentially affects compulsive behavior in rats

Deep brain stimulation (DBS) currently is studied for the treatment of therapy refractory obsessive-compulsive disorder (OCD). DBS may however also serve as an experimental approach in mapping brain regions implicated in OCD pathogenesis. Here, we investigated the involvement of the subthalamic nucleus (STN) in manifestation and treatment of OCD in two rat models of OCD: 1. We studied the effects of bilateral DBS on compulsive checking behavior in the rats quinpirole (QNP) model of OCD and demonstrate that STN-DBS significantly reduced OCD-like behavior. 2. We investigated the effect of bilateral pharmacological inactivation (via muscimol) of the STN and demonstrated an equivalent reduction of OCD like behavior suggesting that the overall mechanism of DBS is of inhibitory nature. 3. We support the specificity of the obtained data by repeating the same experiments in the rats signal attenuation (SA) model of OCD. 4. We studied the effect of bilateral ablative lesions of the STN on the manifestation OCD like behavior in the SA model and showed that ablative lesions of the STN prior to the induction of OCD like behavior led to a significant increase of the same. In conclusion our data give comprehensive evidence for a pathophysiological relevance of the STN in the manifestation of OCD like symptoms in rats and further promote the development of therapeutic alternatives, i.e. STN-DBS, in the treatment of therapy-refractory OCD.

This study was supported by GIF I-851–266.4/2004