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Nigrostriatal Dopaminergic Denervation Does Not Promote Impulsive Choice in the Rat: Implication for Impulse Control Disorders in Parkinson's Disease.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Magnard, Robin 
Vachez, Yvan 
Carcenac, Carole 
Boulet, Sabrina 
Houeto, Jean-Luc 

Abstract

Impulse control disorders (ICDs) are frequent behavioral complications of dopaminergic (DA) replacement therapies (DRTs) in Parkinson's disease (PD). Impulsive choice, which refers to an inability to tolerate delays to reinforcement, has been identified as a core pathophysiological process of ICDs. Although impulsive choices are exacerbated in PD patients with ICDs under DRTs, some clinical and preclinical studies suggest that the DA denervation of the dorsal striatum induced by the neurodegenerative process as well as a pre-existing high impulsivity trait, may both contribute to the emergence of ICDs in PD. We therefore investigated in a preclinical model in rats, specifically designed to study PD-related non-motor symptoms, the effect of nigrostriatal DA denervation on impulsive choice, in relation to pre-existing levels of impulsivity, measured in a Delay Discounting Task (DDT). In this procedure, rats had the choice between responding for a small sucrose reinforcer delivered immediately, or a larger sucrose reinforcer, delivered after a 0, 5, 10 or 15 s delay. In two different versions of the task, the preference for the large reinforcer decreased as the delay increased. However, and in contrast to our initial hypothesis, this discounting effect was neither exacerbated by, or related to, the extent of the substantia nigra pars compacta (SNc) DA lesion, nor it was influenced by pre-existing variability in impulsive choice. These results therefore question the potential implication of the nigrostriatal DA system in impulsive choice, as well as the DA neurodegenerative process as a factor contributing significantly to the development of ICDs in PD.

Description

Keywords

6-OHDA, Parkinson’s disease, delay discounting task, dopaminergic nigrostriatal system, impulse control disorders, impulsive choice, rats

Journal Title

Front Behav Neurosci

Conference Name

Journal ISSN

1662-5153
1662-5153

Volume Title

12

Publisher

Frontiers Media SA
Sponsorship
Wellcome Trust (109738/Z/15/Z)
Medical Research Council (MR/N02530X/1)
MRC