title: 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 (D1, D2, and D3 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 D1R, D2R, and D3R, 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 D1 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 D2 R and D3R 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 D1 R expression may contribute to its therapeutic effects on motor symptoms, whereas its impact on D2R/D3 R levels in the nucleus accumbens may account for the neuropsychiatric side effects often observed in stimulated PD patients, such as postoperative apathy.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France.|Grenoble University, Grenoble, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Carcenac
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France.|Grenoble University, Grenoble, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Favier
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France.|Grenoble University, Grenoble, France.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Vachez
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France.|Grenoble University, Grenoble, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Lacombe
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France.|Grenoble University, Grenoble, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Carnicella
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France.|Grenoble University, Grenoble, France.|Centre Hospitalier Universitaire de Grenoble, Grenoble, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Savasta
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France.|Grenoble University, Grenoble, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Boulet
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D046690:Deep Brain Stimulation; D015259:Dopamine Agents / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects; D007839:Functional Laterality / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011868:Radioisotopes / Q000493:pharmacokinetics; D051381:Rats; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism*; D020531:Subthalamic Nucleus / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D015259:Dopamine Agents; D011868:Radioisotopes; D011954:Receptors, Dopamine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
keywords: Parkinson's disease; dopamine receptors; nucleus accumbens; striatum; subthalamic nucleus high-frequency stimulation