Khanna J M, Chau A, Shah G
Department of Pharmacology, University of Toronto, Canada.
Alcohol. 1996 Nov-Dec;13(6):621-8. doi: 10.1016/s0741-8329(96)00083-3.
Motor impairment (tilt-plane) and hypothermia tests were used to further characterize the phenomenon of rapid tolerance to ethanol. Five experiments were carried out to clarify the relationship between rapid and chronic tolerance. The first experiment demonstrated that the extent of tolerance on day 2 produced by the single dose of 4 g/kg alcohol on day 1 was similar to that resulting from two divided doses, administered 2 h apart. In the second experiment, a linear relationship between treatment dose and rapid tolerance development was demonstrated in that higher day 1 treatment doses resulted in greater rapid tolerance development. In the third, a parallel dose-response relationship, similar to that known for chronic tolerance, was observed for rapid tolerance. In the fourth experiment, we compared the development of rapid tolerance under three different conditions: (a) in groups of rats that were not subjected to testing at all (no testing); on day 1, (b) in groups of rats that were not tested on the apparatus but handled at all test times on day 1 (dummy testing); and (c) in groups of rats that were tested at all test times on day 1 (testing or intoxicated group). No testing on day 1 failed to produce rapid tolerance to ethanol whereas testing and dummy testing of animals on day 1 after pretreatment with ethanol-produced rapid tolerance to ethanol on day 2. In the last experiment, immediate posttrial administration of ketamine was found not to block rapid tolerance development. These findings provide additional support for similarities between the mechanisms of rapid and chronic tolerance.
运动功能损伤（倾斜平面）和体温过低测试被用于进一步描述对乙醇快速耐受的现象。进行了五项实验以阐明快速耐受与慢性耐受之间的关系。第一个实验表明，第1天给予4 g/kg单剂量酒精所产生的第2天的耐受程度，与间隔2小时给予的两次分剂量酒精所产生的耐受程度相似。在第二个实验中，证明了治疗剂量与快速耐受发展之间存在线性关系，即第1天较高的治疗剂量会导致更大程度的快速耐受发展。在第三个实验中，观察到快速耐受存在与慢性耐受已知情况相似的平行剂量反应关系。在第四个实验中，我们比较了三种不同条件下快速耐受的发展情况：（a）在第1天完全不进行测试的大鼠组（无测试）；（b）在第1天不在测试装置上进行测试但在所有测试时间均进行处理的大鼠组（假测试）；以及（c）在第1天所有测试时间均进行测试的大鼠组（测试或中毒组）。第1天不进行测试未能产生对乙醇的快速耐受，而在第1天用乙醇预处理后对动物进行测试和假测试，会在第2天产生对乙醇的快速耐受。在最后一个实验中，发现试验后立即给予氯胺酮并不能阻断快速耐受的发展。这些发现为快速耐受和慢性耐受机制之间的相似性提供了额外支持。
