Laboratoire de Neurobiologie de la Cognition, Centre National de la Recherche Scientifique UMR6155, Aix-Marseille Université, 13331 Marseille, France.
Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1196-200. doi: 10.1073/pnas.0908189107. Epub 2009 Dec 28.
Deep brain stimulation (DBS) is a reversible technique that is currently used for the treatment of Parkinson disease and may be suitable for the treatment of psychiatric disorders. Whether DBS inactivates the target structure is still a matter of debate. Here, from findings obtained in rats, we propose DBS of the subthalamic nucleus (STN) as a possible treatment for cocaine addiction to be further tested in human studies. We show that STN DBS reversibly reduces the motivation to work for an i.v. injection of cocaine, and it increases motivation to work for sucrose pellets. These opposite effects may result from STN DBS effect on the positive affective properties of these rewards. Indeed, we further show that STN DBS reduces the preference for a place previously associated with the rewarding properties of cocaine, and it increases the preference for a place associated with food. Because these findings are consistent with those observed after STN lesions [Baunez C, Dias C, Cador M, Amalric M (2005) Nat Neurosci 8:484-489], they suggest that STN DBS mimics an inactivation of the STN on motivational processes. Furthermore, given that one of the major challenges for cocaine addiction is to find a treatment that reduces the craving for the drug without diminishing the motivation for naturally rewarding activities, our findings validate STN as a good target and DBS as the appropriate technique for a promising therapeutic strategy in the treatment of cocaine addiction.
深部脑刺激(DBS)是一种可逆转的技术,目前用于治疗帕金森病,也可能适用于治疗精神疾病。DBS 是否使目标结构失活仍然存在争议。在这里,我们从大鼠的研究结果中提出,通过刺激丘脑底核(STN)来治疗可卡因成瘾,这一方法需要在人类研究中进一步测试。我们发现,STN 的 DBS 可逆转地降低了对静脉内可卡因注射的工作动机,同时增加了对蔗糖丸的工作动机。这些相反的效果可能是由于 STN DBS 对这些奖励的积极情感属性的影响。事实上,我们进一步发现,STN DBS 降低了对以前与可卡因奖励属性相关的地点的偏好,同时增加了对与食物相关的地点的偏好。由于这些发现与 STN 损伤后观察到的结果一致[Baunez C、Dias C、Cador M、Amalric M(2005)Nat Neurosci 8:484-489],它们表明 STN DBS 模拟了对动机过程中 STN 的失活。此外,鉴于可卡因成瘾的主要挑战之一是找到一种既能减少对药物的渴望,又不会降低对自然奖励活动的动机的治疗方法,我们的发现验证了 STN 作为一个良好的靶点,以及 DBS 作为治疗可卡因成瘾的一种有前途的治疗策略的合适技术。