Rimondini Roberto, Sommer Wolfang H, Dall'Olio Rossella, Heilig Markus
Department of Pharmacology, University of Bologna, Italy.
Addict Biol. 2008 Mar;13(1):26-30. doi: 10.1111/j.1369-1600.2007.00079.x.
Tolerance to alcohol effects is one of the defining features of clinical alcohol dependence. Here, we hypothesized that the post-dependent state may include tolerance to sedative-hypnotic alcohol actions. To address this question, we used a recently developed animal model in which repeated cycles of alcohol intoxication and withdrawal trigger long-lasting behavioral plasticity. This animal model shares important features with the clinical condition. Animals were exposed to 7 weeks of intermittent alcohol vapor, allowed to recover for 3 weeks, and tested in protracted abstinence to exclude contributions from acute withdrawal. Post-dependent and control rats were injected with a hypnotic dose of alcohol (3 g/kg), and the loss of righting reflex (LORR) was recorded, blood alcohol levels were monitored, and the elimination rate was calculated. Post-dependent animals showed a decrease in LORR. Alcohol metabolism and elimination kinetics did not differ between groups. In conclusion, a history of alcohol dependence induces long-lasting hypnotic tolerance. This process may play an important role in maintaining the dependent state.
对酒精作用的耐受性是临床酒精依赖的关键特征之一。在此，我们假设戒断后状态可能包括对酒精镇静催眠作用的耐受性。为解决这个问题，我们使用了一种最近开发的动物模型，其中酒精中毒和戒断的重复循环会引发持久的行为可塑性。这个动物模型与临床情况具有重要的共同特征。动物暴露于7周的间歇性酒精蒸汽中，恢复3周，并在长期戒断状态下进行测试以排除急性戒断的影响。对戒断后的大鼠和对照大鼠注射催眠剂量的酒精（3克/千克），记录翻正反射消失（LORR）情况，监测血液酒精水平，并计算消除率。戒断后的动物LORR降低。两组之间的酒精代谢和消除动力学没有差异。总之，酒精依赖史会诱导长期的催眠耐受性。这个过程可能在维持依赖状态中起重要作用。
