Blum Kenneth, Febo Marcelo, Thanos Panayotis K, Baron David, Fratantonio James, Gold Mark
Department of Psychiatry and McKnight Brain Institute, College of Medicine, University of Florida, P. O. Box 100256, Gainesville, FL, 32610-0256, USA.
Human Integrated Services Unit, Center for Clinical and Translational Science, Department of Psychiatry, College of Medicine, University of Vermont, Burlington, VT, USA.
Mol Neurobiol. 2015 Dec;52(3):1862-1869. doi: 10.1007/s12035-015-9110-9. Epub 2015 Mar 10.
Everyday, there are several millions of people that are increasingly unable to combat their frustrating and even fatal romance with getting high and/or experiencing "normal" feelings of well-being. In the USA, the FDA has approved pharmaceuticals for drug and alcohol abuse: tobacco and nicotine replacement therapy. The National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) remarkably continue to provide an increasing understanding of the intricate functions of brain reward circuitry through sophisticated neuroimaging and molecular genetic applied technology. Similar work is intensely investigated on a worldwide basis with enhanced clarity and increased interaction between not only individual scientists but across many disciplines. However, while it is universally agreed that dopamine is a major neurotransmitter in terms of reward dependence, there remains controversy regarding how to modulate its role clinically to treat and prevent relapse for both substance and non-substance-related addictive behaviors. While the existing FDA-approved medications promote blocking dopamine, we argue that a more prudent paradigm shift should be biphasic-short-term blockade and long-term upregulation, enhancing functional connectivity of brain reward circuits.
每天,都有数百万人越来越难以抗拒他们对吸毒和/或体验“正常”幸福感的那种令人沮丧甚至致命的沉迷。在美国,美国食品药品监督管理局(FDA)已批准了用于药物和酒精滥用的药物:烟草和尼古丁替代疗法。美国国家药物滥用研究所(NIDA)和美国国家酒精滥用与酒精中毒研究所(NIAAA)通过先进的神经成像和分子遗传学应用技术,持续深入地增进了对大脑奖赏回路复杂功能的理解。全球范围内都在积极开展类似的研究,不仅个体科学家之间,而且跨学科之间的研究都更加清晰,互动也更多。然而,尽管人们普遍认为多巴胺是奖赏依赖方面的主要神经递质,但在临床上如何调节其作用以治疗和预防物质相关及非物质相关成瘾行为的复发方面,仍存在争议。虽然现有的FDA批准药物促进多巴胺阻断,但我们认为更谨慎的范式转变应该是双相的——短期阻断和长期上调,增强大脑奖赏回路的功能连接性。