The role of the subthalamic nucleus in 'compulsive' behavior in rats.
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.
Winter
Christine
C
Department of Psychiatry and Psychotherapy, Charité Campus Mitte, University Medicine, Berlin, Germany.
Flash
Shira
S
Klavir
Oded
O
Klein
Julia
J
Sohr
Reinhard
R
Joel
Daphna
D
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*
D012701:Serotonin; D004298:Dopamine