Reta Lila Weston Institute of Neurological Studies, University College London, London WC1N 1PJ, UK.
Brain. 2011 Apr;134(Pt 4):969-78. doi: 10.1093/brain/awr003. Epub 2011 Feb 24.
Impulsive-compulsive behaviours are a significant source of morbidity for patients with Parkinson's disease receiving dopaminergic therapy. The development of these behaviours may reflect sensitization of the neural response to non-drug rewards, similar to that proposed for sensitization to drug rewards in addiction. Here, by using (11)C-raclopride positron emission tomography imaging, we investigated the effects of reward-related cues and L-dopa challenge in patients with Parkinson's disease with and without impulsive-compulsive behaviours on striatal levels of synaptic dopamine. Eighteen patients (11 with and seven without impulsive-compulsive behaviours) underwent three (11)C-raclopride positron emission tomography scans. The impulsive-compulsive behaviours included hypersexuality, binge eating, punding, compulsive use of dopamine replacement therapy, compulsive buying and pathological gambling, with eight patients exhibiting more than one impulsive-compulsive behaviour. There were no significant differences in baseline dopamine D2 receptor availability between the Parkinson's disease groups. No differences were found when comparing the percentage change of raclopride binding potential between the two Parkinson's disease groups following L-dopa challenge with neutral cues. The group with Parkinson's disease with impulsive-compulsive behaviours had a greater reduction of ventral striatum (11)C-raclopride binding potential following reward-related cue exposure, relative to neutral cue exposure, following L-dopa challenge (16.3% compared with 5.8% in Parkinson's disease controls, P = 0.016). The heightened response of striatal reward circuitry to heterogeneous reward-related visual cues among a group of patients with different impulsive-compulsive behaviours is consistent with a global sensitization to appetitive behaviours with dopaminergic therapy in vulnerable individuals. Our findings are relevant for the broader debate on the relation between impulsive-compulsive behaviours and addictions and may have important implications with regards to advertisement legislation in an effort to prevent the onset of behavioural addictions.
冲动-强迫行为是接受多巴胺能治疗的帕金森病患者发病率的重要来源。这些行为的发展可能反映了对非药物奖励的神经反应的敏感化，类似于对成瘾药物奖励的敏感化。在这里，我们通过使用 (11)C-racopride 正电子发射断层扫描成像，研究了有和没有冲动-强迫行为的帕金森病患者在纹状体突触多巴胺水平上，与奖励相关的线索和 L-多巴挑战的影响。18 名患者（11 名有冲动-强迫行为，7 名无冲动-强迫行为）接受了三次 (11)C-racopride 正电子发射断层扫描检查。冲动-强迫行为包括性欲亢进、暴食、强迫性打游戏、强迫性使用多巴胺替代疗法、强迫性购物和病理性赌博，其中 8 名患者表现出一种以上的冲动-强迫行为。两组帕金森病患者的基线多巴胺 D2 受体可用性没有显著差异。在 L-多巴挑战与中性线索后，两组帕金森病患者之间的 racopride 结合潜力的百分比变化没有差异。在 L-多巴挑战后，有冲动-强迫行为的帕金森病组在暴露于奖励相关线索时，腹侧纹状体的 (11)C-racopride 结合潜力较中性线索时减少更多（16.3%对帕金森病对照组的 5.8%，P=0.016）。在一组具有不同冲动-强迫行为的患者中，纹状体奖励回路对异质奖励相关视觉线索的反应增强，这与多巴胺能治疗在易感性个体中对食欲行为的普遍敏感化一致。我们的发现与冲动-强迫行为和成瘾之间的广泛争论有关，并且可能对广告立法方面具有重要意义，以努力防止行为成瘾的发生。
