title: Implication of dorsostriatal D3 receptors in motivational processes: a potential target for neuropsychiatric symptoms in Parkinson's disease.
abstract: Beyond classical motor symptoms, motivational and affective deficits are frequently observed in Parkinson's disease (PD), dramatically impairing the quality of life of patients. Using bilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc) in rats, we have been able to reproduce these neuropsychiatric/non-motor impairments. The present study describes how bilateral 6-OHDA SNc lesions affect the function of the main striatal dopaminergic (DA) receptor subtypes. Autoradiography was used to measure the levels of striatal DA receptors, and operant sucrose self-administration and neuropharmacological approaches were combined to investigate the causal implication of specific DA receptors subtypes in the motivational deficits induced by a dorsostriatal DA denervation. We found that D3 receptors (D3R) exclusively are down-regulated within the dorsal striatum of lesioned rats. We next showed that infusion of a D3R antagonist (SB-277011A) in non-lesioned animals specifically disrupts preparatory, but not consummatory behaviors. Our findings reveal an unexpected involvement of dorsostriatal D3R in motivational processes. They strongly suggest an implication of dorsostriatal D3R in the neuropsychiatric symptoms observed in PD, highlighting this receptor as a potential target for pharmacological treatment.
authors.affiliation: Inserm, U1216, F- 38000 Grenoble, France.|Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Favier
authors.affiliation: Inserm, U1216, F- 38000 Grenoble, France.|Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Carcenac
authors.affiliation: Inserm, U1216, F- 38000 Grenoble, France.|Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Drui
authors.affiliation: Inserm, U1216, F- 38000 Grenoble, France.|Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Vachez
authors.affiliation: Inserm, U1216, F- 38000 Grenoble, France.|Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Boulet
authors.affiliation: Inserm, U1216, F- 38000 Grenoble, France.|Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France.|Centre Hospitalier Universitaire de Grenoble, BP217, Grenoble F-38043, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Savasta
authors.affiliation: Inserm, U1216, F- 38000 Grenoble, France.|Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Carnicella
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015870:Gene Expression; D007150:Immunohistochemistry; D008297:Male; D016627:Oxidopamine / Q000009:adverse effects; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology; D013395:Sucrose / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D050637:Receptors, Dopamine D3; D013395:Sucrose; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine