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Multi-facetted impulsivity following nigral degeneration and dopamine replacement therapy.
Neuropharmacology. 2016 10; 109:69-77.N

Abstract

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.

Authors+Show Affiliations

Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000, Bordeaux, France.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.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.Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000, Bordeaux, France.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.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: pierre-olivier.fernagut@u-bordeaux.fr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27216859

Citation

Engeln, Michel, et al. "Multi-facetted Impulsivity Following Nigral Degeneration and Dopamine Replacement Therapy." Neuropharmacology, vol. 109, 2016, pp. 69-77.
Engeln M, Ansquer S, Dugast E, et al. Multi-facetted impulsivity following nigral degeneration and dopamine replacement therapy. Neuropharmacology. 2016;109:69-77.
Engeln, M., Ansquer, S., Dugast, E., Bezard, E., Belin, D., & Fernagut, P. O. (2016). Multi-facetted impulsivity following nigral degeneration and dopamine replacement therapy. Neuropharmacology, 109, 69-77. https://doi.org/10.1016/j.neuropharm.2016.05.013
Engeln M, et al. Multi-facetted Impulsivity Following Nigral Degeneration and Dopamine Replacement Therapy. Neuropharmacology. 2016;109:69-77. PubMed PMID: 27216859.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multi-facetted impulsivity following nigral degeneration and dopamine replacement therapy. AU - Engeln,Michel, AU - Ansquer,Solène, AU - Dugast,Emilie, AU - Bezard,Erwan, AU - Belin,David, AU - Fernagut,Pierre-Olivier, Y1 - 2016/05/20/ PY - 2016/02/17/received PY - 2016/05/17/revised PY - 2016/05/19/accepted PY - 2016/5/25/entrez PY - 2016/5/25/pubmed PY - 2017/6/20/medline KW - Alpha-synuclein KW - Impulsivity KW - Parkinson KW - Pramipexole KW - Substantia nigra SP - 69 EP - 77 JF - Neuropharmacology JO - Neuropharmacology VL - 109 N2 - 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. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/27216859/Multi_facetted_impulsivity_following_nigral_degeneration_and_dopamine_replacement_therapy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(16)30211-8 DB - PRIME DP - Unbound Medicine ER -