In recent years there have been several attempts to establish high frequency stimulation (HFS) as an additional treatment strategy for obsessive-compulsive disorder (OCD). Two studies reported that bilateral HFS of the subthalamic nucleus (STN) dramatically alleviated compulsions and improved obsessions in three patients with co-morbid Parkinson's disease and OCD. A recent study reported that HFS as well as pharmacological inactivation of the STN alleviate compulsive checking in the quinpirole rat model of OCD. As the quinpirole model is based on a dopaminergic manipulation, the aim of the present study was to test whether HFS and pharmacological inactivation of the STN exert an anti-compulsive effect also in the drug-naive brain, using the signal attenuation rat model of OCD. The main finding of the present study is that both HFS and pharmacological inactivation of the STN exerted an anti-compulsive effect, although the two manipulations differed in their effects on other behavioral measures. These findings support the possibility that HFS of the STN may provide an additional therapeutic strategy for OCD.