Dardou David, Chassain Carine, Durif Franck
EA7280 NPSY-Sydo, Université d'Auvergne Clermont-Ferrand, France.
IRM-Hopital Gabriel Montpied Clermont-Ferrand, France.
Front Neurosci. 2015 Jan 6;8:437. doi: 10.3389/fnins.2014.00437. eCollection 2014.
The loss of dopamine neurons observed in Parkinson's disease (PD) elicits severe motor control deficits which are reduced by the use of dopamine agonists. However, recent works have indicated that D3-preferential agonists such as pramipexole can induce impulse control disorders (ICDs) such as food craving or compulsive eating. In the present study, we performed an intermittent daily feeding experiment to assess the effect of chronic treatment by pramipexole and VTA bilateral lesion on tolerance for sucrose solution. The impact of such chronic treatment on spontaneous locomotion and spatial memory was also examined. Changes in sucrose tolerance could indicate the potential development of a change in food compulsion or addiction related to the action of pramipexole. Neither the bilateral lesion of the VTA nor chronic treatment with pramipexole altered the spontaneous locomotion or spatial memory in rats. Rats without pramipexole treatment quickly developed a stable intake of sucrose solution in the 12 h access phase. On the contrary, when under daily pramipexole treatment, rats developed a stronger and ongoing escalation of their sucrose solution intakes. In addition, we noted that the change in sucrose consumption was sustained by an increase of the expression of the Dopamine D3 receptor in the core and the shell regions of the nucleus accumbens. The present results may suggest that long-term stimulation of the Dopamine D3 receptor in animals induces a strong increase in sucrose consumption, indicating an effect of this receptor on certain pathological aspects of food eating.
在帕金森病（PD）中观察到的多巴胺能神经元缺失会引发严重的运动控制缺陷，而使用多巴胺激动剂可减轻这些缺陷。然而，最近的研究表明，像普拉克索这样的D3选择性激动剂会诱发冲动控制障碍（ICD），如食物渴望或强迫性进食。在本研究中，我们进行了一项间歇性每日喂食实验，以评估普拉克索慢性治疗和腹侧被盖区（VTA）双侧损伤对蔗糖溶液耐受性的影响。还研究了这种慢性治疗对自发运动和空间记忆的影响。蔗糖耐受性的变化可能表明与普拉克索作用相关的食物强迫或成瘾性变化的潜在发展。VTA双侧损伤和普拉克索慢性治疗均未改变大鼠的自发运动或空间记忆。未接受普拉克索治疗的大鼠在12小时进食阶段迅速形成了稳定的蔗糖溶液摄入量。相反，在每日接受普拉克索治疗时，大鼠的蔗糖溶液摄入量出现了更强且持续的增加。此外，我们注意到伏隔核核心区和壳区多巴胺D3受体表达的增加维持了蔗糖消耗的变化。目前的结果可能表明，长期刺激动物体内的多巴胺D3受体会导致蔗糖消耗大幅增加，表明该受体对进食的某些病理方面有影响。
