Department of Psychology, University of North Carolina, Chapel Hill, NC 27599-3270, USA.
CNS Neurol Disord Drug Targets. 2010 Mar;9(1):77-86. doi: 10.2174/187152710790966605.
Alcoholism is a chronic disorder characterized by cycling periods of excessive ethanol consumption, withdrawal, abstinence and relapse, which is associated with progressive changes in central corticotropin-releasing factor (CRF) receptor signaling. CRF and urocortin peptides act by binding to the CRF type 1 (CRF1R) or the CRF type 2 (CRF2R) receptors, both of which have been implicated in the regulation of neurobiological responses to ethanol. The current review provides a comprehensive overview of preclinical evidence from studies involving rodents that when viewed together, suggest a promising role for CRFR antagonists in the treatment of alcohol abuse disorders. CRFR antagonists protect against excessive ethanol intake resulting from ethanol dependence without influencing ethanol intake in non-dependent animals. Similarly, CRFR antagonists block excessive binge-like ethanol drinking in non-dependent mice but do not alter ethanol intake in mice drinking moderate amounts of ethanol. CRFR antagonists also protect against increased ethanol intake and relapse-like behaviors precipitated by exposure to a stressful event. Additionally, CRFR antagonists attenuate the negative emotional responses associated with ethanol withdrawal. The protective effects of CRFR antagonists are modulated by CRF1R. Finally, recent evidence has emerged suggesting that CRF2R agonists may also be useful for treating alcohol abuse disorders.
酒精中毒是一种慢性疾病，其特征是周期性地过度饮酒、戒断、禁欲和复发，这与中枢促肾上腺皮质激素释放因子（CRF）受体信号的进行性变化有关。CRF 和尿皮质素肽通过与 CRF 型 1（CRF1R）或 CRF 型 2（CRF2R）受体结合而发挥作用，这两种受体都与调节对乙醇的神经生物学反应有关。目前的综述提供了一个全面的综述，从涉及啮齿动物的临床前研究证据来看，这些证据表明 CRFR 拮抗剂在治疗酒精滥用障碍方面具有很大的潜力。CRFR 拮抗剂可预防因乙醇依赖而导致的过度乙醇摄入，而不影响非依赖动物的乙醇摄入。同样，CRFR 拮抗剂可阻断非依赖小鼠的过度 binge 样乙醇摄入，但不改变饮用适量乙醇的小鼠的乙醇摄入。CRFR 拮抗剂还可预防因暴露于应激事件而导致的乙醇摄入增加和复发样行为。此外，CRFR 拮抗剂可减轻与乙醇戒断相关的负面情绪反应。CRFR 拮抗剂的保护作用受 CRF1R 调节。最后，最近的证据表明，CRF2R 激动剂也可能对治疗酒精滥用障碍有用。
