Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation.
Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation.
复制标题
DOI：
10.1016/j.tips.2016.08.002
复制
发表时间：
2016-11
影响因子：
13.8
通讯作者：
Evans CJ
中科院分区：
文献类型：
--
作者：
Cahill CM;Walwyn W;Taylor AMW;Pradhan AAA;Evans CJ
阿片类药物耐受的机制主要集中在含有阿片类药物受体的细胞内的适应性修饰，这里定义为细胞动态平衡，强调阿片类药物受体信号体的调节。我们回顾了行为耐受性中涉及的其他监管和对手过程，包括激动剂之间（激动剂偏差）以及μ-和δ-阿片受体之间的机制差异。在我们称之为传递变稳态的过程中，直接由阿片类药物修饰的细胞将变稳态变化归因于下游电路。由于阿片类药物系统的广泛分布，在阿片类药物依赖/耐受状态下，每个脑细胞都可能受到前向失衡的影响。我们将把神经元和小胶质细胞作为累积的调节过程的交互贡献者，从而产生对阿片类药物的镇痛和享乐耐受。
Mechanisms of opioid tolerance have focused on adaptive modifications within cells containing opioid receptors, defined here as cellular allostasis, emphasizing regulation of the opioid receptor signalosome. We review additional regulatory and opponent processes involved in behavioral tolerance, and include mechanistic differences both between agonists (agonist bias), and between μ- and δ-opioid receptors. In a process we will refer to as pass-forward allostasis, cells modified directly by opioid drugs impute allostatic changes to downstream circuitry. Because of the broad distribution of opioid systems, every brain cell may be touched by pass-forward allostasis in the opioid-dependent/tolerant state. We will implicate neurons and microglia as interactive contributors to the cumulative allostatic processes creating analgesic and hedonic tolerance to opioid drugs.