Discipline of Physiology, School of Medical Sciences, University of Adelaide, Level 5, Medical School South, Frome Rd, Adelaide, South Australia 5005, Australia.
Neuropharmacology. 2014 Jan;76 Pt B(0 0):218-27. doi: 10.1016/j.neuropharm.2013.05.039. Epub 2013 Jun 11.
A major development in drug addiction research in recent years has been the discovery that immune signaling within the central nervous system contributes significantly to mesolimbic dopamine reward signaling induced by drugs of abuse, and hence is involved in the presentation of reward behaviors. Additionally, in the case of opioids, these hypotheses have advanced through to the discovery of the novel site of opioid action at the innate immune pattern recognition receptor Toll-like receptor 4 as the necessary triggering event that engages this reward facilitating central immune signaling. Thus, the hypothesis of major proinflammatory contributions to drug abuse was born. This review will examine these key discoveries, but also address several key lingering questions of how central immune signaling is able to contribute in this fashion to the pharmacodynamics of drugs of abuse. It is hoped that by combining the collective wisdom of neuroscience, immunology and pharmacology, into Neuroimmunopharmacology, we may more fully understanding the neuronal and immune complexities of how drugs of abuse, such as opioids, create their rewarding and addiction states. Such discoveries will point us in the direction such that one day soon we might successfully intervene to successfully treat drug addiction. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.
近年来，药物成瘾研究的一个主要进展是发现中枢神经系统内的免疫信号对滥用药物引起的中脑边缘多巴胺奖赏信号有重要贡献，因此与奖赏行为的表现有关。此外，就阿片类药物而言，这些假设已经通过在先天免疫模式识别受体 Toll 样受体 4 上发现阿片类药物作用的新位点而得到推进，该受体是激活这种促进奖赏的中枢免疫信号的必需触发事件。因此，主要的促炎作用导致药物滥用的假设诞生了。这篇综述将检查这些关键发现，但也将解决几个关于中枢免疫信号如何以这种方式对滥用药物的药效学做出贡献的关键遗留问题。希望通过将神经科学、免疫学和药理学的集体智慧结合到神经免疫药理学中，我们可以更充分地了解阿片类药物等滥用药物如何产生奖赏和成瘾状态的神经元和免疫复杂性。这些发现将为我们指明方向，有朝一日我们或许能够成功干预，从而成功治疗药物成瘾。本文是题为“NIDA 40 周年特刊”的特刊的一部分。
