Chu Kathleen, Koob George F, Cole Maury, Zorrilla Eric P, Roberts Amanda J
Molecular and Integrative Neurosciences Department, SV 142, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92036, USA.
Pharmacol Biochem Behav. 2007 Apr;86(4):813-21. doi: 10.1016/j.pbb.2007.03.009. Epub 2007 Apr 3.
Models of dependence-induced increases in ethanol self-administration will be critical in increasing our understanding of the processes of addiction and relapse, underlying mechanisms, and potential therapeutics. One system that has received considerable attention recently is the CRF(1) system that may mediate the link between anxiety states and relapse drinking. C57BL/6J mice were trained to lever press for ethanol, were made dependent and then were allowed to self-administer ethanol following a period of abstinence. The effect of the CRF(1) antagonist, antalarmin, was examined on this abstinence-induced self-administration in a separate group of mice. Finally, dependence-induced changes in ethanol self-administration were examined in CRF(1) knockout and wild type mice. The results indicated that ethanol self-administration was increased following the induction of dependence, but only after a period of abstinence. This increase in ethanol self-administration was blocked by antalarmin. Furthermore, CRF(1) knockout mice did not display this increased ethanol self-administration following dependence and abstinence. These studies, using both a pharmacological and genetic approach, support a critical role for the CRF(1) system in ethanol self-administration following dependence. In addition, a model is presented that may be useful for studies examining underlying mechanisms of the ethanol addiction process as well as for testing potential therapeutics.
依赖诱导乙醇自我给药增加的模型对于增进我们对成瘾和复发过程、潜在机制及潜在治疗方法的理解至关重要。最近受到相当多关注的一个系统是促肾上腺皮质激素释放因子（CRF）(1)系统，它可能介导焦虑状态与复发性饮酒之间的联系。对C57BL/6J小鼠进行训练，使其通过按压杠杆获取乙醇，使其产生依赖性，然后在一段禁欲期后让其自我给药乙醇。在另一组小鼠中，研究了CRF(1)拮抗剂安他拉明对这种禁欲诱导的自我给药的影响。最后，在CRF(1)基因敲除小鼠和野生型小鼠中研究了依赖诱导的乙醇自我给药变化。结果表明，在诱导依赖性后，乙醇自我给药增加，但仅在一段禁欲期后。安他拉明阻断了乙醇自我给药的这种增加。此外，CRF(1)基因敲除小鼠在依赖和禁欲后并未表现出乙醇自我给药的增加。这些研究采用药理学和遗传学方法，支持CRF(1)系统在依赖后乙醇自我给药中起关键作用。此外，还提出了一个模型，该模型可能有助于研究乙醇成瘾过程的潜在机制以及测试潜在治疗方法。
