Daniel Baugh Institute for Functional Genomics and Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Daniel Baugh Institute for Functional Genomics and Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Neurosci Biobehav Rev. 2021 Jun;125:355-364. doi: 10.1016/j.neubiorev.2021.02.033. Epub 2021 Feb 26.
Alcohol and opioids are two major contributors to so-called deaths of despair. Though the effects of these substances on mammalian systems are distinct, commonalities in their withdrawal syndromes suggest a shared pathophysiology. For example, both are characterized by marked autonomic dysregulation and are treated with alpha-2 agonists. Moreover, alcohol and opioids rapidly induce dependence motivated by withdrawal avoidance. Resemblances observed in withdrawal syndromes and abuse behavior may indicate common addiction mechanisms. We argue that neurovisceral feedback influences autonomic and emotional circuits generating antireward similarly for both substances. Amygdala is central to this hypothesis as it is principally responsible for negative emotion, prominent in addiction and motivated behavior, and processes autonomic inputs while generating autonomic outputs. The solitary nucleus (NTS) has strong bidirectional connections to the amygdala and receives interoceptive inputs communicating visceral states via vagal afferents. These visceral-emotional hubs are strongly influenced by the periphery including gut microbiota. We propose that gut dysbiosis contributes to alcohol and opioid withdrawal syndromes by contributing to peripheral and neuroinflammation that stimulates these antireward pathways and motivates substance dependence.
酒精和阿片类药物是所谓“绝望之死”的两大主要原因。尽管这些物质对哺乳动物系统的影响是不同的，但它们戒断综合征的共同点表明存在共同的病理生理学。例如，两者都以明显的自主神经失调为特征，并采用α-2 激动剂进行治疗。此外，酒精和阿片类药物会迅速引起依赖，以避免戒断。在戒断综合征和滥用行为中观察到的相似之处可能表明存在共同的成瘾机制。我们认为，神经内脏反馈会影响自主和情绪回路，从而为这两种物质产生类似的抗奖赏效应。杏仁核是这一假设的核心，因为它主要负责产生负面情绪，在成瘾和动机行为中表现突出，并在产生自主输出的同时处理自主输入。孤束核（NTS）与杏仁核有很强的双向连接，通过迷走神经传入纤维接收内脏状态的内脏传入。这些内脏-情绪中枢受到包括肠道微生物群在内的外周的强烈影响。我们提出，肠道菌群失调通过促进外周和神经炎症来促进酒精和阿片类药物戒断综合征，从而刺激这些抗奖赏途径并促使物质依赖。
