Subthalamic deep brain stimulation differently alters striatal dopaminergic receptor levels in rats

Abstract High‐frequency stimulation (HFS) of the subthalamic nucleus (STN) is recognized as an effective treatment for the motor symptoms of Parkinson's disease (PD), but its mechanisms, particularly as concern dopaminergic transmission, remain unclear. The aim of this study was to evaluate changes in the expression of dopaminergic receptors (D 1 , D 2 , and D 3 receptors) after prolonged (4 h) unilateral STN‐HFS in anesthetized intact rats and rats with total dopaminergic denervation. We used [ 3 H]SCH 23390, [ 125 I]iodosulpride, and [ 125 I]OH‐PIPAT to assess the densities of D 1 R, D 2 R, and D 3 R, respectively, within different areas of the striatum—a major input structure of the basal ganglia—including the nucleus accumbens. We found that STN‐HFS increased D 1 R levels in almost all of the striatal areas examined, in both intact and denervated rats. By contrast, STN‐HFS led to a large decrease in D 2 R and D 3 R levels, limited to the nucleus accumbens and independent of the dopaminergic state of the animals. These data suggest that the influence of STN‐HFS on striatal D 1 R expression may contribute to its therapeutic effects on motor symptoms, whereas its impact on D 2 R/D 3 R levels in the nucleus accumbens may account for the neuropsychiatric side effects often observed in stimulated PD patients, such as postoperative apathy. © 2015 International Parkinson and Movement Disorder Society