Koob G F, Wall T L, Schafer J
Division of Preclinical Neuroscience and Endocrinology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Alcohol. 1987 Nov-Dec;4(6):481-4. doi: 10.1016/0741-8329(87)90090-5.
Tolerance to ethanol was tested with 24 adult, male, Wistar rats using a modified Geller-Seifter paradigm. This design consisted of three components: an unpunished random interval-30 sec (RI-30) schedule, a time-out period, and a punished plus continuous reinforcement (conflict) schedule. This procedure allowed for a distinction to be made between the sedative and the "anxiolytic" effects of ethanol. Rats were trained on this procedure until response rates stabilized. They were then randomly divided into three groups. One group served as a control group for two experiments. In the first experiment, the test group received ethanol (0.75 g/kg IP) on days 2-8 and saline on days 1 and 9. For the second experiment, the control group received saline and the test group received ethanol three times in one day at three hour intervals. The "anxiolytic" action (defined as an increase in the rate of punished responding or antipunishment effect) was observed to undergo rapid tolerance (by day 4 in experiment one and by the second session in experiment two), while tolerance to the sedative action (defined as a decrease in the rate of unpunished responding) developed more slowly (only by day 7 in experiment one, but by the third session in experiment two). These results suggest that rapid tolerance develops to the "anxiolytic" actions of ethanol and this may have important implications for the development of ethanol abuse.
使用改良的盖勒-塞弗特范式,对24只成年雄性Wistar大鼠进行乙醇耐受性测试。该设计包括三个部分:无惩罚的随机间隔30秒(RI-30)时间表、暂停期和惩罚加连续强化(冲突)时间表。该程序允许区分乙醇的镇静作用和“抗焦虑”作用。大鼠按照此程序进行训练,直到反应率稳定。然后将它们随机分为三组。一组作为两个实验的对照组。在第一个实验中,测试组在第2至8天接受乙醇(0.75 g/kg腹腔注射),在第1天和第9天接受生理盐水。在第二个实验中,对照组接受生理盐水,测试组在一天内每隔三小时接受三次乙醇。观察到“抗焦虑”作用(定义为惩罚反应率增加或抗惩罚效应)迅速产生耐受性(在实验一中到第4天,在实验二中到第二阶段),而对镇静作用的耐受性(定义为无惩罚反应率降低)发展较慢(在实验一中仅到第7天,但在实验二中到第三阶段)。这些结果表明,乙醇的“抗焦虑”作用迅速产生耐受性,这可能对乙醇滥用的发展具有重要意义。