McGinn M Adrienne, Pantazis Caroline B, Tunstall Brendan J, Marchette Renata C N, Carlson Erika R, Said Nadia, Koob George F, Vendruscolo Leandro F
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, United States.
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, United States.
Int Rev Neurobiol. 2021;157:409-472. doi: 10.1016/bs.irn.2020.11.002. Epub 2021 Feb 13.
Addiction is a chronic disorder that consists of a three-stage cycle of binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. These stages involve, respectively, neuroadaptations in brain circuits involved in incentive salience and habit formation, stress surfeit and reward deficit, and executive function. Much research on addiction focuses on the neurobiology underlying single drug use. However, alcohol use disorder (AUD) can be co-morbid with substance use disorder (SUD), called dual dependence. The limited epidemiological data on dual dependence indicates that there is a large population of individuals suffering from addiction who are dependent on more than one drug and/or alcohol, yet dual dependence remains understudied in addiction research. Here, we review neurobiological data on neurotransmitter and neuropeptide systems that are known to contribute to addiction pathology and how the involvement of these systems is consistent or divergent across drug classes. In particular, we highlight the dopamine, opioid, corticotropin-releasing factor, norepinephrine, hypocretin/orexin, glucocorticoid, neuroimmune signaling, endocannabinoid, glutamate, and GABA systems. We also discuss the limited research on these systems in dual dependence. Collectively, these studies demonstrate that the use of multiple drugs can produce neuroadaptations that are distinct from single drug use. Further investigation into the neurobiology of dual dependence is necessary to develop effective treatments for addiction to multiple drugs.
成瘾是一种慢性疾病，由三个阶段的循环组成：暴饮暴食/中毒、戒断/负面影响以及专注/期待。这些阶段分别涉及参与动机显著性和习惯形成的脑回路中的神经适应性变化、应激过剩和奖励不足以及执行功能。许多关于成瘾的研究都集中在单一药物使用的神经生物学基础上。然而，酒精使用障碍（AUD）可能与物质使用障碍（SUD）共病，即双重依赖。关于双重依赖的有限流行病学数据表明，有大量成瘾者依赖不止一种药物和/或酒精，但双重依赖在成瘾研究中仍未得到充分研究。在此，我们综述了已知对成瘾病理有影响的神经递质和神经肽系统的神经生物学数据，以及这些系统在不同药物类别中的参与情况是如何一致或不同的。特别是，我们重点介绍了多巴胺、阿片类、促肾上腺皮质激素释放因子、去甲肾上腺素、下丘脑分泌素/食欲素、糖皮质激素、神经免疫信号、内源性大麻素、谷氨酸和γ-氨基丁酸系统。我们还讨论了这些系统在双重依赖方面的有限研究。总体而言，这些研究表明，使用多种药物会产生与单一药物使用不同的神经适应性变化。进一步研究双重依赖的神经生物学对于开发针对多种药物成瘾的有效治疗方法是必要的。
