High frequency stimulation of the subthalamic nucleus reduces quinpirole induced compulsive checking behavior in rats

Obsessive compulsive disorder (OCD) is one of the most common psychiatric afflictions predominantly presenting with compulsive checking. Functional MRI studies have implicated the cortical-striatal-thalamic-cortical circuits and the mesiotemporal lobe in the pathophysiology of OCD. Congruently, in patients remaining unaffected by pharmaco- and psychotherapy controversially discussed partial ablative lesioning of these circuits can reverse clinical symptoms. In the treatment of other neuro-psychiatric disorders ablative lesioning has majorly been replaced by the selective and reversible high frequency stimulation (HFS). The overall mechanism underlying HFS has been proposed to be a functional inhibition of neuronal activity in the region stimulated.

The subthalamic nucleus (STN) is one of the neuroanatomical components in the basal ganglia which are known to be essential for motor functions. The STN is involved in associative, limbic and motor cortical and subcortical loops. Inactivation of the STN via HFS may consequently affect motor as well as non-motor behavioural functions. Accordingly, recent studies implicate that STN-HFS also influences various non-motor aspects of behaviour, such as cognition, mood and motivation. Furthermore, it has been demonstrated that STN-HFS reduces checking behavior in two PD patients also suffering from OCD like symptoms. In order to further elucidate the ethiopathological role of the STN in the manifestation of OCD we investigated the effect of bilateral STN-HFS on induction and reduction of checking behavior in the rat's quinpirole (QNP) model of OCD. We demonstrate that STN-HFS reduces quinpirole induced compulsive checking behavior but does not prevent the induction of OCD like symptoms in rats. We conclude that a functional inhibition of the STN can selectively antagonize compulsive checking behavior in the quinpirole animal model of OCD and suggest that a hyperactive STN may be involved in but ethiopathologically not essential for the manifestation of compulsive checking behavior in the rat's quinpirole model of OCD.

Sponsored by DFG (Ku 830/3) and EC(QLK6–1999–02173)