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.

SUBMITTER: Favier M 

PROVIDER: S-EPMC5278505 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature