Multi-facetted impulsivity following nigral degeneration and dopamine replacement therapy.
Neuropharmacology. 2016-10-01; 109: 69-77
DOI: 10.1016/j.neuropharm.2016.05.013
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1. Neuropharmacology. 2016 Oct;109:69-77. doi: 10.1016/j.neuropharm.2016.05.013.
Epub 2016 May 20.
Multi-facetted impulsivity following nigral degeneration and dopamine replacement
therapy.
Engeln M(1), Ansquer S(2), Dugast E(3), Bezard E(1), Belin D(4), Fernagut PO(5).
Author information:
(1)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR
5293, F-33000, Bordeaux, France.
(2)Service de neurologie de l’hôpital de Poitiers, F-86021, Poitiers, France;
Université de Poitiers, F-86000, Poitiers, France; CIC INSERM 1402, CHU de
Poitiers, Poitiers, France.
(3)Université de Poitiers, F-86000, Poitiers, France; CIC INSERM 1402, CHU de
Poitiers, Poitiers, France; INSERM U1084 Laboratoire de Neurosciences
Experimentales et Cliniques, F-86000, Poitiers, France.
(4)INSERM U1084 Laboratoire de Neurosciences Experimentales et Cliniques,
F-86000, Poitiers, France; Department of Pharmacology, University of Cambridge,
CB2 1PD, Cambridge, UK; Behavioural and Clinical Neuroscience Institute of the
University of Cambridge, CB2 3ED, Cambridge, UK.
(5)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR
5293, F-33000, Bordeaux, France. Electronic address:
.
Impulse control disorders (ICDs) are debilitating side effects of dopamine
replacement therapy (DRT) in Parkinson’s disease (PD) that severely affect the
quality of life of patients. While DRT, the pattern and extent of
neurodegeneration, and prodromic factors of vulnerability (e.g. impulsivity) have
all been hypothesized to play a role in the development of ICDs, their
respective, and potentially interacting, contributions remain to be established.
High impulsive (HI), Intermediate (Int) or low impulsive (LI) rats were
identified based on their performance in both a differential reinforcement of low
rate of responding (DRL) and a fixed consecutive number (FCN) schedules, that
operationalize two independent facets of impulsivity, waiting and action
inhibition (motor impulsivity). We investigated whether high impulsivity trait
influenced the progressive development of a parkinsonian state induced by
viral-mediated overexpression of α-synuclein, and whether impulsivity trait and
nigrostriatal neurodegeneration independently or jointly influenced the effects
of DRT on impulse control. α-synuclein-induced nigrostriatal neurodegeneration
increased both waiting and motor impulsivity. The D2/D3 dopamine receptor agonist
pramipexole exacerbated motor impulsivity more than waiting. However, the
pramipexole-induced increase in waiting impulsivity observed in both sham and
lesioned rats, was more pronounced in HI lesioned rats, which displayed a
restricted α-synuclein-induced dopaminergic neurodegeneration. Thus, a PD-like
nigrostriatal lesion increases both motor and waiting impulsivity, but its
interaction with a pre-existing impulsivity trait, which, at the cellular level,
confers resilience to dopaminergic neurodegeneration, worsens the detrimental
effects of D2/D3 dopamine receptor agonists on inhibitory control.
Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
DOI: 10.1016/j.neuropharm.2016.05.013
PMCID: PMC5405054
PMID: 27216859 [Indexed for MEDLINE]