Regarding "Dynorphin is a downstream effector of striatal BDNF regulation of ethanol intake".
Regarding "Dynorphin is a downstream effector of striatal BDNF regulation of ethanol intake".
复制标题
关于“强啡肽是纹状体 BDNF 调节乙醇摄入量的下游效应器”。
DOI：
10.1096/fj.08-0702ltr
复制
发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Koob,GeorgeF
中科院分区：
文献类型：
--
作者：
Walker,BrendanM;Koob,GeorgeF
在阅读了M. Logrip，P. Janak，and D.罗恩于2008年2月29日在线发表在《FASEB杂志》上，注意到该手稿的讨论部分引用了我们的工作，重点是κ-阿片受体和强啡肽系统在乙醇依赖和戒断中的作用（1）。不幸的是，我们的研究结果和指导研究的假设似乎在Logrip等人的讨论部分中被误解了。手稿（2）。我们想澄清的是，我们实验中的行为观察结果表明，用nor-binaltorphimine（nor-BNI）阻断κ-阿片受体选择性地减少了乙醇依赖性动物的乙醇自我给药;使非依赖性动物的乙醇自我给药行为保持不变（Logrip等人的手稿指出，我们通过阻断强啡肽系统观察到乙醇自我给药增加）。此外，我们在该手稿中提出，强啡肽系统在乙醇依赖状态下具有增加的活性。据推测，当乙醇依赖性动物处于戒断状态时，强啡肽系统的活性增加会产生负面情感/烦躁状态，乙醇自我给药通过负强化机制缓解。通过用nor-BNI阻断乙醇戒断期间这种purone上调的强啡肽状态，暂时消除了由过度活跃的强啡肽系统产生的负面情绪状态，并降低了继续自我施用乙醇的需要。
Upon reading the interesting article by M. Logrip, P. Janak, and D. Ron that was published online on February 29th, 2008, in [and appears in this issue of] The FASEB Journal, it was noticed that a section of that manuscript’s discussion section referenced our work focusing on the role of κ-opioid receptors and dynorphin systems in ethanol dependence and withdrawal (1). Unfortunately, both the results of our study and the hypothesis that guided the research appear to have been misunderstood within the discussion section of the Logrip et al. manuscript (2). We would like to clarify that the behavioral observations from our experiments indicated that blockade of κ-opioid receptors with nor-binaltorphimine (nor-BNI) selectively decreased ethanol self-administration in ethanol-dependent animals; leaving self-administration behavior of ethanol in nondependent animals intact (the Logrip et al. manuscript stated we observed increases in ethanol selfadministration by blocking dynorphin systems). Additionally, we proposed in that manuscript that the dynorphin system has increased activity in ethanol dependent states. It is hypothesized that when ethanol-dependent animals are in withdrawal, the increased activity of the dynorphin system produces a negative affective/dysphoric state that ethanol self-administration relieves via a negative reinforcement mechanism. By blocking this putatively upregulated dynorphin state during ethanol withdrawal with nor-BNI, the negative emotional state produced by an overactive dynorphin system is removed temporarily and the need to continue self-administering ethanol is lowered.