Walker Brendan M, Rasmussen Dennis D, Raskind Murray A, Koob George F
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037, USA.
Alcohol. 2008 Mar;42(2):91-7. doi: 10.1016/j.alcohol.2007.12.002.
The purpose of this study was to test the hypothesis that blockade of alpha1-adrenergic receptors may suppress the excessive ethanol consumption associated with acute withdrawal in ethanol-dependent rats. Following the acquisition and stabilization of operant ethanol self-administration in male Wistar rats, dependence was induced in half the animals by subjecting them to a 4-week intermittent vapor exposure period in which animals were exposed to ethanol vapor for 14h/day. Subsequent to dependence induction, the effect of alpha1-noradrenergic receptor antagonist prazosin (0.0, 0.25, 0.5, 1, 1.5, and 2.0mg/kg IP) was tested on operant responding for ethanol in vapor-exposed and control rats during acute withdrawal. In ethanol-dependent animals, prazosin significantly suppressed responding at the 1.5 and 2.0mg/kg doses, whereas only the 2.0mg/kg dose was effective in nondependent animals, identifying an increase in the sensitivity to prazosin in dependent animals. Conversely, at the lowest dose tested (0.25mg/kg), prazosin increased responding in nondependent animals, which is consistent with the effect of anxiolytics on ethanol self-administration in nondependent animals. None of the doses tested reliably affected concurrent water self-administration. These results suggest the involvement of the noradrenergic system in the excessive alcohol drinking seen during acute withdrawal in ethanol-dependent rats.
阻断α1-肾上腺素能受体可能会抑制乙醇依赖大鼠急性戒断时的过度乙醇摄入。在雄性Wistar大鼠中建立并稳定操作性乙醇自我给药后，将一半动物置于4周的间歇性蒸汽暴露期以诱导其产生依赖性，在此期间动物每天暴露于乙醇蒸汽中14小时。在诱导依赖性之后，测试α1-去甲肾上腺素能受体拮抗剂哌唑嗪（0.0、0.25、0.5、1、1.5和2.0mg/kg腹腔注射）对急性戒断期间蒸汽暴露大鼠和对照大鼠乙醇操作性反应的影响。在乙醇依赖动物中，哌唑嗪在1.5和2.0mg/kg剂量时显著抑制反应，而在非依赖动物中只有2.0mg/kg剂量有效，这表明依赖动物对哌唑嗪的敏感性增加。相反，在测试的最低剂量（0.25mg/kg）时，哌唑嗪增加了非依赖动物的反应，这与抗焦虑药对非依赖动物乙醇自我给药的作用一致。所测试的任何剂量均未可靠地影响同时进行的水自我给药。这些结果表明去甲肾上腺素能系统参与了乙醇依赖大鼠急性戒断期间的过度饮酒。
