O'Sullivan Sean J, Malahias Evangelia, Park James, Srivastava Ankita, Reyes Beverly A S, Gorky Jon, Vadigepalli Rajanikanth, Van Bockstaele Elisabeth J, Schwaber James S
Daniel Baugh Institute for Functional Genomics and Computational Biology, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, United States.
Department of Chemical Engineering, University of Delaware, Newark, DE, United States.
Front Neurosci. 2019 Jul 3;13:665. doi: 10.3389/fnins.2019.00665. eCollection 2019.
Drug-seeking in opioid dependence is due in part to the severe negative emotion associated with the withdrawal syndrome. It is well-established that negative emotional states emerge from activity in the amygdala. More recently, gut microflora have been shown to contribute substantially to such emotions. We measured gene expression in single glia and neurons gathered from the amygdala using laser capture microdissection and simultaneously measured gut microflora in morphine-dependent and withdrawn rats to investigate drivers of negative emotion in opioid withdrawal. We found that neuroinflammatory genes, notably , were upregulated in the withdrawal condition and that astrocytes, in particular, were highly active. We also observe a decreased to ratio in opioid withdrawal indicating gut dysbiosis. We speculate that these inflammatory and gut microflora changes contribute to the negative emotion experienced in opioid withdrawal that motivates dependence.
在阿片类药物依赖中,寻求药物的行为部分归因于与戒断综合征相关的严重负面情绪。众所周知,负面情绪状态源于杏仁核的活动。最近,肠道微生物群已被证明对这类情绪有很大影响。我们使用激光捕获显微切割技术测量了从杏仁核收集的单个神经胶质细胞和神经元中的基因表达,并同时测量了吗啡依赖和戒断大鼠的肠道微生物群,以研究阿片类药物戒断中负面情绪的驱动因素。我们发现,在戒断状态下,神经炎症基因,特别是 ,上调,并且星形胶质细胞尤其活跃。我们还观察到阿片类药物戒断中 与 比率降低,表明肠道微生物群失调。我们推测,这些炎症和肠道微生物群的变化导致了阿片类药物戒断中产生的负面情绪,这种情绪促使了药物依赖。