Manzanares Jorge, Ortiz Sergio, Oliva José M, Pérez-Rial Sandra, Palomo Tomás
Edificio Materno-Infantil, Planta 6, 613-A, Hospital Universitario 12 de Octubre, Avda. Cordoba s/n, 28041 Madrid, Spain.
Alcohol Alcohol. 2005 Jan-Feb;40(1):25-34. doi: 10.1093/alcalc/agh112. Epub 2004 Nov 18.
Over the past few years, advances in the investigation of the neurochemical circuits involved in the development and treatment of alcohol dependence have identified peptides and receptors as potential key targets in the treatment of problems related to alcohol consumption. The endogenous opioid system is modified by alcohol intake in areas of the brain related to reward systems, and differential basal levels of opioid gene expression are found in rodents with a high preference for ethanol. This suggests a greater vulnerability to alcohol consumption in relation to differences in genetic background. Further evidence of the involvement of opioid peptides in alcohol dependence is the ability of the opioid antagonist naltrexone to reduce alcohol intake in animal models of dependence and in alcohol-dependent patients. Abundant evidence indicates that the activation of cannabinoid receptors stimulates the release of opioid peptides, therefore the cannabinoid receptor antagonists may presumably alter opioid peptide release, thus facilitating the reduction of ethanol consumption. However, little is known about the effects of ethanol on the endogenous cannabinoid system, the vulnerability of cannabinoid receptors to alcohol intake or their neurochemical implications in reducing consumption of alcohol. In this paper, we review the role of opioid and cannabinoid receptor systems, their vulnerability to alcohol intake and the development of dependence, and the targeting of these systems in the treatment of alcoholism.
在过去几年中，对参与酒精依赖发展与治疗的神经化学回路的研究进展已将肽类和受体确定为治疗与饮酒相关问题的潜在关键靶点。内源性阿片系统在大脑中与奖赏系统相关的区域会因酒精摄入而发生改变，并且在对乙醇有高度偏好的啮齿动物中发现了阿片类基因表达的基础水平差异。这表明，相对于遗传背景的差异，个体对酒精消费的易感性更高。阿片肽参与酒精依赖的进一步证据是，阿片拮抗剂纳曲酮能够在依赖动物模型和酒精依赖患者中减少酒精摄入量。大量证据表明，大麻素受体的激活会刺激阿片肽的释放，因此大麻素受体拮抗剂可能会改变阿片肽的释放，从而有助于减少乙醇消费。然而，关于乙醇对内源性大麻素系统的影响、大麻素受体对酒精摄入的易感性或它们在减少酒精消费方面的神经化学意义，我们所知甚少。在本文中，我们综述了阿片和大麻素受体系统的作用、它们对酒精摄入和依赖发展的易感性，以及这些系统在酒精中毒治疗中的靶向作用。
