title: The role of the subthalamic nucleus in 'compulsive' behavior in rats.
abstract: Different lines of evidence point to dysfunction of basal ganglia-thalamocortical circuits in obsessive-compulsive disorder (OCD). It has been hypothesized that the circuits' dysfunction in OCD may be characterized by a relative under-activity of the indirect compared with the direct pathway within these circuits. The present study tested whether lesions of the subthalamic nucleus (STN), a major node of the indirect pathway, would affect compulsive behavior, using the signal attenuation rat model of OCD. In this model, compulsive lever-pressing is induced by the attenuation of an external signal of reward delivery; an attenuation that is hypothesized to simulate the deficient response feedback suggested to underlie obsessions and compulsions in patients with OCD. Rats sustaining lesions to the STN showed a selective increase in compulsive lever-pressing compared with sham-operated rats. A post mortem biochemical analysis revealed a decrease in serotonin content in the prelimbic and infralimbic cortices, caudate-putamen (but not nucleus accumbens), globus pallidus and substantia nigra-ventral tegmental area, as well as a decrease in dopamine content in the caudate-putamen in STN-lesioned compared with sham rats. A comparison to recent findings that lesions to the orbitofrontal cortex, which also result in a selective increase in compulsive lever-pressing, lead to a decrease in serotonin and dopamine content in the caudate-putamen suggests that there may be a final common pathway by which different brain pathologies may lead to a pro-compulsive state.
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Campus Mitte, University Medicine, Berlin, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Winter
authors.forename: Shira
authors.initials: S
authors.lastname: Flash
authors.forename: Oded
authors.initials: O
authors.lastname: Klavir
authors.forename: Julia
authors.initials: J
authors.lastname: Klein
authors.forename: Reinhard
authors.initials: R
authors.lastname: Sohr
authors.forename: Daphna
authors.initials: D
authors.lastname: Joel
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003192:Compulsive Behavior / Q000378:metabolism* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D009771:Obsessive-Compulsive Disorder / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012701:Serotonin / Q000378:metabolism*; D020531:Subthalamic Nucleus / Q000293:injuries / Q000378:metabolism*
chemical_list: D012701:Serotonin; D004298:Dopamine