Table_10_Single-Cell Glia and Neuron Gene Expression in the Central Amygdala in Opioid Withdrawal Suggests Inflammation With Correlated Gut Dysbiosis.XLSX

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the amygdala using laser capture microdissection and simultaneously measured gut microflora in morphine-dependent and withdrawn rats to investigate drivers of negative emotion in opioid withdrawal.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 Tnf, were upregulated in the withdrawal condition and that astrocytes, in particular, were highly active. We also observe a decreased Firmicutes to Bacteroides 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.

阿片类药物依赖者的觅药行为，部分源于戒断综合征伴随的剧烈负性情绪。已有研究证实，负性情绪状态的产生与杏仁核（amygdala）的神经活动密切相关。近年来的研究进一步表明，肠道菌群（gut microflora）在这类情绪的调控中发挥着重要作用。本研究通过激光捕获显微切割（laser capture microdissection）技术，采集来自杏仁核的单个神经胶质细胞与神经元以检测其基因表达情况；同时对吗啡依赖及戒断大鼠的肠道菌群进行检测，旨在探究阿片类戒断反应中负性情绪的驱动因素。研究结果显示，戒断状态下神经炎症相关基因（尤其是Tnf）表达上调，且星形胶质细胞（astrocytes）的激活程度显著升高。本研究同时观察到，阿片类戒断状态下厚壁菌门（Firmicutes）与拟杆菌属（Bacteroides）的比值降低，提示存在肠道菌群失调。据此我们推测，上述神经炎症与肠道菌群的变化，可能参与介导阿片类戒断过程中引发依赖行为的负性情绪。