Department of Molecular Medicine, Scripps Research Institute, La Jolla, California.
Alcohol Res. 2022 Jan 27;42(1):03. doi: 10.35946/arcr.v42.1.03. eCollection 2022.
A growing body of evidence has implicated the endocannabinoid (eCB) system in the acute, chronic, and withdrawal effects of alcohol/ethanol on synaptic function. These eCB-mediated synaptic effects may contribute to the development of alcohol use disorder (AUD). Alcohol exposure causes neurobiological alterations similar to those elicited by chronic cannabinoid (CB) exposure. Like alcohol, cannabinoids alter many central processes, such as cognition, locomotion, synaptic transmission, and neurotransmitter release. There is a strong need to elucidate the effects of ethanol on the eCB system in different brain regions to understand the role of eCB signaling in AUD.
For the scope of this review, preclinical studies were identified through queries of the PubMed database.
This search yielded 459 articles. Clinical studies and papers irrelevant to the topic of this review were excluded.
The endocannabinoid system includes, but is not limited to, cannabinoid receptors 1 (CB), among the most abundantly expressed neuronal receptors in the brain; cannabinoid receptors 2 (CB); and endogenously formed CB ligands, including arachidonoylethanolamide (AEA; anandamide), and 2-arachidonoylglycerol (2-AG). The development of specific CB agonists, such as WIN 55,212-2 (WIN), and antagonists, such as SR 141716A (rimonabant), provide powerful pharmacological tools for eCB research. Alcohol exposure has brain region-specific effects on the eCB system, including altering the synthesis of endocannabinoids (e.g., AEA, 2-AG), the synthesis of their precursors, and the density and coupling efficacy of CB. These alcohol-induced alterations of the eCB system have subsequent effects on synaptic function including neuronal excitability and postsynaptic conductance. This review will provide a comprehensive evaluation of the current literature on the synaptic interactions of alcohol exposure and eCB signaling systems, with an emphasis on molecular and physiological synaptic effects of alcohol on the eCB system. A limited volume of studies has focused on the underlying interactions of alcohol and the eCB system at the synaptic level in the brain. Thus, the data on synaptic interactions are sparse, and future research addressing these interactions is much needed.
越来越多的证据表明内源性大麻素（eCB）系统参与了酒精/乙醇对突触功能的急性、慢性和戒断效应。这些 eCB 介导的突触效应可能有助于酒精使用障碍（AUD）的发展。酒精暴露引起的神经生物学改变与慢性大麻素（CB）暴露引起的改变相似。像酒精一样，大麻素会改变许多中枢过程，如认知、运动、突触传递和神经递质释放。为了阐明乙醇对不同脑区 eCB 系统的影响，需要深入了解 eCB 信号在 AUD 中的作用。
为了进行本综述，通过查询 PubMed 数据库确定了预实验研究。
该检索共产生 459 篇文章。排除了与本综述主题无关的临床研究和论文。
内源性大麻素系统包括但不限于大脑中表达最丰富的神经元受体之一大麻素受体 1（CB1）；大麻素受体 2（CB2）；以及内源性形成的 CB 配体，包括花生四烯酸乙醇酰胺（AEA；大麻素）和 2-花生四烯酸甘油（2-AG）。特定 CB 激动剂（如 WIN 55,212-2（WIN））和拮抗剂（如 SR 141716A（利莫那班））的开发为 eCB 研究提供了强大的药理学工具。酒精暴露对 eCB 系统具有脑区特异性影响，包括改变内源性大麻素（如 AEA、2-AG）的合成、其前体的合成以及 CB 的密度和偶联效率。这些酒精诱导的 eCB 系统改变随后对突触功能产生影响，包括神经元兴奋性和突触后电导。本综述将全面评估目前关于酒精暴露和 eCB 信号系统突触相互作用的文献，重点关注酒精对 eCB 系统的分子和生理突触效应。有限数量的研究集中在大脑中酒精和 eCB 系统在突触水平上的潜在相互作用。因此，关于突触相互作用的数据很少，非常需要开展未来的研究。
