Pramipexole-induced impulsivity in mildparkinsonian rats: a model of impulse control disorders in Parkinson's disease

被引:18
|
作者
Jimenez-Urbieta, Haritz [1 ,2 ]
Gago, Belen [1 ,2 ,10 ]
Quiroga-Varela, Ana [1 ,2 ]
Rodriguez-Chinchilla, Tatiana [1 ,2 ]
Merino-Galan, Leyre [1 ,2 ,3 ]
Oregi, Amaia [1 ,2 ]
Belloso-Iguerategui, Arantzazu [1 ,2 ]
Delgado-Alvarado, Manuel [1 ,2 ]
Navalpotro-Gomez, Irene [1 ,2 ]
Marin, Concepcio [4 ]
Fernagut, Pierre-Olivier [5 ,6 ]
Rodriguez-Oroz, Maria C. [1 ,2 ,7 ,8 ,9 ]
机构
[1] Inst Invest Sanitaria Biodonostia, Area Neurociencias, San Sebastian, Spain
[2] CIBERNED, Madrid, Spain
[3] Univ Pais Vasco UPV EHU, Dept Neurociencias, Leioa, Spain
[4] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain
[5] Univ Bordeaux, Inst Malad Neurodegenerat, CNRS, UMR 5293, Bordeaux, France
[6] Univ Poitiers, Lab Neurosci Expt & Clin, INSERM, U1084, Poitiers, France
[7] Ikerbasque Fdn, Bilbao, Spain
[8] Basque Ctr Cognit Brain & Language, San Sebastian, Spain
[9] Clin Univ Navarra, Ctr Appl Med Res CIMA, Pamplona, Spain
[10] Univ Malaga, Inst Invest Biomed Malaga, Fac Med, Campus Teatinos S-N, E-29071 Malaga, Spain
关键词
Parkinson's disease; Impulse control disorders; Pramipexole; 5-choice serial reaction time task; alpha-synuclein; FosB/Delta FosB; REACTION-TIME-TASK; L-DOPA; INTERTEMPORAL CHOICE; NUCLEUS-ACCUMBENS; RODENT MODEL; MODULATION; EXPRESSION; BEHAVIORS; DYSKINESIAS; PERFORMANCE;
D O I
10.1016/j.neurobiolaging.2018.11.021
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Treatment with dopaminergic agonists such as pramipexole (PPX) contributes to the development of impulse control disorders (ICDs) in patients with Parkinson's disease (PD). As such, animal models of abnormal impulse control in PD are needed to better study the pathophysiology of these behaviors. Thus, we investigated impulsivity and related behaviors using the 5-choice serial reaction time task, as well as FosB/Delta FosB expression, in rats with mild parkinsonism induced by viral-mediated substantia nigra overexpression of human A53T mutated alpha-synuclein, and following chronic PPX treatment (0.25 mg/kg/d) for 4 weeks. The bilateral loss of striatal dopamine transporters (64%) increased the premature response rate of these rats, indicating enhanced waiting impulsivity. This behavior persisted in the OFF state after the second week of PPX treatment and it was further exacerbated in the ON state throughout the treatment period. The enhanced rate of premature responses following dopaminergic denervation was positively correlated with the premature response rate following PPX treatment (both in the ON and OFF states). Moreover, the striatal dopaminergic deficit was negatively correlated with the premature response rate at all times (pretreatment, ON and OFF states) and it was positively correlated with the striatal FosB/Delta FosB expression. By contrast, PPX treatment was not associated with changes in compulsivity (perseverative responses rate). This model recapitulates some features of PD with ICD, namely the dopaminergic deficit of early PD and the impulsivity traits provoked by dopaminergic loss in association with PPX treatment, making this model a useful tool to study the pathophysiology of ICDs. (C) 2018 Elsevier Inc. All rights reserved.
引用
收藏
页码:126 / 135
页数:10
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