Amelioration of binge eating by nucleus accumbens shell deep brain stimulation in mice involves D2 receptor modulation.
Amelioration of binge eating by nucleus accumbens shell deep brain stimulation in mice involves D2 receptor modulation.
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DOI：
10.1523/jneurosci.3237-12.2013
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发表时间：
2013-04-24
期刊：
影响因子：
--
通讯作者：
Bale TL
中科院分区：
文献类型：
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作者：
Halpern CH;Tekriwal A;Santollo J;Keating JG;Wolf JA;Daniels D;Bale TL
导致肥胖的享乐性过度消费与中脑边缘多巴胺系统的激活改变有关。伏隔核壳（NAS）多巴胺信号的失调与奖励寻求行为有关，如暴饮暴食，这有助于肥胖的治疗抵抗。用深部脑刺激（DBS）直接调节NAS，一种目前正在研究的用于治疗重度抑郁症、强迫症和成瘾的外科手术方法，也可能有效地改善暴饮暴食。因此，我们在小鼠中检测了NAS的DBS阻断这种行为的能力。c-Fos免疫反应性被评估为dbs介导的神经元激活的标志。NAS DBS可以减少暴饮暴食，并增加该区域的c-Fos水平。背纹状体的DBS对这种行为没有影响，证明了这种作用的解剖学特异性。多巴胺D2受体拮抗剂raclopride可以减弱DBS的作用，而D1受体拮抗剂SCH-23390则无效，这表明多巴胺信号通路涉及D2受体是NAS DBS作用的基础。为了确定与肥胖状态的潜在翻译相关性，慢性NAS DBS也在饮食诱导的肥胖小鼠中进行了研究，发现它可以急剧减少热量摄入并诱导体重减轻。综上所述，这些发现支持中边缘多巴胺通路参与导致肥胖的享乐机制，以及NAS DBS调节该系统的功效。
Hedonic over-consumption contributing to obesity involves altered activation within the mesolimbic dopamine system. Dysregulation of dopamine signaling in the nucleus accumbens shell (NAS) has been implicated in reward-seeking behaviors, such as binge eating, which contributes to treatment resistance in obesity. Direct modulation of the NAS with deep brain stimulation (DBS), a surgical procedure currently under investigation in humans for the treatment of major depression, obsessive-compulsive disorder, and addiction, may also be effective in ameliorating binge eating. Therefore, we examined the ability of DBS of the NAS to block this behavior in mice. c-Fos immunoreactivity was assessed as a marker of DBS-mediated neuronal activation. NAS DBS was found to reduce binge eating, and increased c-Fos levels in this region. DBS of the dorsal striatum had no influence on this behavior, demonstrating anatomical specificity for this effect. The dopamine D2 receptor antagonist, raclopride, attenuated the action of DBS, while the D1 receptor antagonist, SCH-23390, was ineffective, suggesting that dopamine signaling involving D2 receptors underlies the effect of NAS DBS. To determine the potential translational relevance to the obese state, chronic NAS DBS was also examined in diet-induced obese mice, and was found to acutely reduce caloric intake and induce weight loss. Taken together, these findings support the involvement of the mesolimbic dopamine pathways in the hedonic mechanisms contributing to obesity, and the efficacy of NAS DBS to modulate this system.