Loiodice Simon, Winlow Poppy, Dremier Sarah, Hanon Etienne, Dardou David, Ouachikh Omar, Hafidi Aziz, da Costa Andre Nogueira, Durif Franck
UFR Medicine, Université d'Auvergne, 28 Place Henri Dunant, 63000, Clermont-Ferrand, France.
Department of Non-Clinical Development, UCB Biopharma SPRL, Chemin du Foriest 1, 1420, Braine-l'Alleud, Belgium.
Psychopharmacology (Berl). 2017 Jan;234(1):15-27. doi: 10.1007/s00213-016-4430-7. Epub 2016 Sep 10.
Impulsive-compulsive disorders (ICD) in patients with Parkinson's disease (PD) have been described as behavioral or substance addictions including hypersexuality, gambling, or compulsive medication use of the dopamine replacement therapy (DRT).
A remaining challenge is to understand the neuroadaptations leading to reward bias in PD patients under DRT.
To this end, the appetitive effect of the D2/D3 agonist pramipexole was assessed after chronic exposure to L-dopa in an alpha-synuclein PD rat model.
Association of progressive nigral loss and chronic L-dopa was required to observe a pramipexole-induced place preference. This behavioral outcome was inhibited by metabotropic glutamate receptor 5 (mGluR5) antagonism while transcriptional profiling highlighted regulations potentially related to the context of psychostimulant addiction.
This study provides evidences strongly suggesting that PD-like lesion and L-dopa therapy were concomitant factors involved in striatal remodeling underlying the pramipexole-induced place preference. Molecular and pharmacological data suggest a key involvement of the glutamatergic pathway in this behavioral outcome.
帕金森病（PD）患者的冲动控制障碍（ICD）被描述为行为或物质成瘾，包括性欲亢进、赌博或多巴胺替代疗法（DRT）的强迫性药物使用。
一个尚存的挑战是了解导致接受DRT的PD患者出现奖赏偏差的神经适应性变化。
为此，在α-突触核蛋白PD大鼠模型中，评估了长期暴露于左旋多巴后D2/D3激动剂普拉克索的奖赏效应。
需要渐进性黑质损伤与长期左旋多巴联用，才能观察到普拉克索诱导的位置偏爱。代谢型谷氨酸受体5（mGluR5）拮抗剂可抑制这一行为结果，而转录谱分析突出了可能与精神兴奋剂成瘾背景相关的调控。
本研究提供的证据有力地表明，类似PD的损伤和左旋多巴治疗是普拉克索诱导的位置偏爱背后纹状体重塑的伴随因素。分子和药理学数据表明谷氨酸能通路在这一行为结果中起关键作用。
