Translating the neuroscience of alcoholism into clinical treatments: from blocking the buzz to curing the blues.
Translating the neuroscience of alcoholism into clinical treatments: from blocking the buzz to curing the blues.
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DOI：
10.1016/j.neubiorev.2009.11.018
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发表时间：
2010-11
影响因子：
8.2
通讯作者：
Barr, Christina S.
中科院分区：
文献类型：
--
作者：
Heilig, Markus;Thorsell, Annika;Sommer, Wolfgang H.;Hansson, Anita C.;Ramchandani, Vijay A.;George, David T.;Hommer, Daniel;Barr, Christina S.
关键词：
了解成瘾性疾病的病理生理学对于开发新疗法至关重要。长期以来，成瘾研究的一个主要焦点一直是介导成瘾药物急性正强化作用的系统，其中最突出的是中脑边缘多巴胺能（DA）系统及其连接。该研究系列成功地揭示了自然和药物奖励的生理学，但尚未带来治疗突破。经典奖励系统在酒精成瘾中的作用可能最不明确。在此，对最近的工作进行了总结，指出了一些临床上重要的结论。首先，在酒精的积极增强作用和该药物激活经典奖赏途径的能力方面存在重要的药理学差异。这为酗酒的个性化治疗方法提供了机会。其次，大脑压力和恐惧系统在酗酒的后期病理性地激活，它们的激活对酒精摄入量的增加、压力反应的敏感度和复发的易感性有重大影响。这些发现提供了一类新的治疗机制。通过 CRH1 受体的促肾上腺皮质激素释放激素 (CRH) 信号传导是此类中的主要候选靶标，但最近的数据表明 P 物质 (SP) 神经激肽 1 (NK1) 受体的拮抗剂可能具有类似的潜力。
Understanding the pathophysiology of addictive disorders is critical for development of new treatments. A major focus of addiction research has for a long time been on systems that mediate acute positively reinforcing effects of addictive drugs, most prominently the mesolimbic dopaminergic (DA) system and its connections. This research line has been successful in shedding light on the physiology of both natural and drug reward, but has not led to therapeutic breakthroughs. The role of classical reward systems is perhaps least clear in alcohol addiction. Here, recent work is summarized that points to some clinically important conclusions. First, important pharmacogenetic differences exist with regard to positively reinforcing effects of alcohol and the ability of this drug to activate classical reward pathways. This offers an opportunity for personalized treatment approaches in alcoholism. Second, brain stress and fear systems become pathologically activated in later stages of alcoholism and their activation is a major influence in escalation of alcohol intake, sensitization of stress responses, and susceptibility to relapse. These findings offer a new category of treatment mechanisms. Corticotrophin-releasing hormone (CRH) signaling through CRH1 receptors is a major candidate target in this category, but recent data indicate that antagonists for substance P (SP) neurokinin 1 (NK1) receptors may have a similar potential.
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影响因子：
5
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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