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Implication of dorsostriatal D3 receptors in motivational processes

on the May 24, 2017

A potential target for neuropsychiatric symptoms in Parkinson's disease

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, researchers from "Physiopathology of Motivation" group 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.

They found that D3 receptors (D3R) exclusively are down-regulated within the dorsal striatum of lesioned rats. They next showed that infusion of a D3R antagonist (SB-277011A) in non-lesioned animals specifically disrupts preparatory, but not consummatory behaviors. Their 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.

 

Distribution of D3 receptors in the striatum of a control (left) and parkinsonian (right) rat.

References: 

[1] Drui G, Carnicella S, Carcenac C, Favier M, Bertrand A, Boulet S, Savasta M (2014) Loss of dopaminergic nigrostriatal neurons accounts for the motivational and affective deficits in Parkinson's disease. Molecular Psychiatry 19(3):358-67.

[2] Favier M, Duran T, Drui G, Carcenac C, Savasta M, Carnicella S (2014) Full reversion of motivational deficits by pramipexole in a rodent model of Parkinson’s disease. Mov Disord, 7:912-20.

[3] Favier M, Carcenac C, Drui G, Vachez Y, Boulet S, Savasta M, Carnicella S (2017). Implication of dorsostriatal D3 receptors in motivational processes: a potential target for neuropsychiatric symptoms in Parkinson's disease. Sci Rep. 2017 Jan 30;7:41589. doi: 10.1038/srep41589.



Updated on December 8, 2017

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