Mackenzie-Taylor D, Rech R H
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Pharmacol Biochem Behav. 1991 Jan;38(1):29-36. doi: 10.1016/0091-3057(91)90585-p.
Four groups of rats received ethanol: 1) intermittently while experiencing hypothermia, 2) chronically while experiencing hypothermia, 3) intermittently while protected from hypothermia, and 4) chronically while being protected from hypothermia. On postchronic testing, Group 1 showed tolerance to 2.0 and 2.3 but not 2.7 g/kg ethanol, Group 2 was tolerant to all 3 doses, Group 3 was tolerant to none, and Group 4 was tolerant only to 2.7 g/kg. On withdrawal of chronic ethanol or vehicle, Groups 1 and 2 showed trends to lose tolerance which became significant after subsequent extinction training. The treatments were repeated in other rats up to the postchronic test for tolerance, after which they were killed at 15-120 min after ethanol to assay serum and brain concentrations. Serum and brain levels of ethanol were higher in Groups 2 and 4 despite less intense hypothermia (i.e., no metabolic tolerance). Analysis of covariance indicated less tolerance in Group 1 vs. Group 2 and Group 3 vs. Group 4 for the same brain levels of ethanol (i.e., cellular tolerance in Groups 2 and 4). Therefore, both learned and cellular tolerances were observed in these subjects and appeared to be separable phenomena according to the various treatments imposed.
1）在体温过低时间歇性给予；2）在体温过低时长期给予；3）在防止体温过低时间歇性给予；4）在防止体温过低时长期给予。在长期处理后的测试中，第1组对2.0和2.3 g/kg乙醇表现出耐受性，但对2.7 g/kg乙醇无耐受性；第2组对所有3种剂量均有耐受性；第3组均无耐受性；第4组仅对2.7 g/kg有耐受性。在停用长期给予的乙醇或赋形剂后，第1组和第2组表现出耐受性丧失的趋势，在随后的消退训练后这种趋势变得显著。在其他大鼠中重复这些处理直至进行长期处理后的耐受性测试，之后在给予乙醇后15 - 120分钟将它们处死，以测定血清和脑内浓度。尽管体温过低程度较轻（即无代谢耐受性），但第2组和第4组的血清和脑内乙醇水平较高。协方差分析表明，对于相同脑内乙醇水平，第1组相对于第2组以及第3组相对于第4组的耐受性较低（即第2组和第4组存在细胞耐受性）。因此，在这些实验对象中观察到了习得性耐受性和细胞耐受性，并且根据所施加的各种处理，它们似乎是可分离的现象。
