Funk Cindy K, Koob George F
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA.
Brain Res. 2007 Jun 25;1155:172-8. doi: 10.1016/j.brainres.2007.04.009. Epub 2007 Apr 10.
Alcohol dependence is characterized by excessive consumption, loss of control over intake and the presence of a withdrawal syndrome, including both motivational and physical symptoms. Previous studies have implicated the brain corticotropin-releasing factor (CRF) stress systems in mediating the negative emotional state associated with ethanol withdrawal. CRF(1) receptor-specific antagonists, administered systemically, and CRF receptor subtype nonspecific antagonists, administered into the central nucleus of the amygdala (CeA), selectively decrease the anxiety-like behaviors and increased ethanol self-administration associated with ethanol withdrawal. In the present study, we investigated the role of CRF(2) receptors within the CeA in mediating ethanol self-administration in ethanol-dependent and nondependent animals. Male Wistar rats were made dependent on ethanol using an intermittent ethanol vapor exposure paradigm. Nondependent animals received similar conditions but were exposed to air only. Following 2 h of withdrawal from ethanol vapors, ethanol and water self-administration were measured following administration of urocortin 3, a highly selective CRF(2) agonist, in the CeA. In dependent rats, urocortin 3 (0.1 microg/microl and 0.5 microg/microl) decreased ethanol self-administration, with no effect on water self-administration. In nondependent rats, urocortin 3 (0.5 microg/microl) increased ethanol self-administration, with no effect on water self-administration. These data demonstrate an opposing role of the CRF(2) receptor subtype within the CeA in mediating ethanol self-administration in withdrawn, dependent and nondependent rats.
酒精依赖的特征是饮酒过量、无法控制饮酒量以及出现戒断综合征，包括动机和身体症状。先前的研究表明，大脑促肾上腺皮质激素释放因子（CRF）应激系统在介导与乙醇戒断相关的负面情绪状态中起作用。全身给药的CRF(1)受体特异性拮抗剂和杏仁核中央核（CeA）给药的CRF受体亚型非特异性拮抗剂，可选择性降低与乙醇戒断相关的焦虑样行为，并增加乙醇自我给药量。在本研究中，我们调查了CeA内CRF(2)受体在介导乙醇依赖和非依赖动物的乙醇自我给药中的作用。使用间歇性乙醇蒸气暴露范式使雄性Wistar大鼠对乙醇产生依赖。非依赖动物接受相似条件，但仅暴露于空气中。从乙醇蒸气中戒断2小时后，在CeA中注射urocortin 3（一种高度选择性的CRF(2)激动剂）后，测量乙醇和水的自我给药量。在依赖大鼠中，urocortin 3（0.1微克/微升和0.5微克/微升）减少了乙醇自我给药量，而对水的自我给药量没有影响。在非依赖大鼠中，urocortin 3（0.5微克/微升）增加了乙醇自我给药量，而对水的自我给药量没有影响。这些数据表明，CeA内的CRF(2)受体亚型在介导戒断、依赖和非依赖大鼠的乙醇自我给药中具有相反的作用。
