Khanna J M, Kalant H, Lê A D, LeBlanc A E
Adv Exp Med Biol. 1980;132:779-86. doi: 10.1007/978-1-4757-1419-7_81.
Adult male Wistar rats were fed nutritionally adequate liquid diets providing 35% of the total calories as ethanol, while pair-fed controls received the corresponding diet with ethanol replaced by an equicaloric concentration of sucrose. After 2, 4, 6, 8, 10 and 14 weeks of chronic ethanol treatment, separate groups of rats were injected with a test dose of either ethanol (3 g/kg) or pentobarbital (40 mg/kg). Rectal temperatures were determined prior to and at 30, 60, 90 and 120 min after injection. The fall in rectal temperature after a test dose of ethanol or pentobarbital was significantly lower at 2 and 4 weeks in ethanol-treated rats than in pair-fed controls. After 6 and 8 weeks of chronic ethanol treatment, the fall in temperature after the same test doses was still less in ethanol-treated rats than in controls. However, at 10 and 14 weeks the fall in temperature was virtually identical in the two groups. A similar pattern of results was obtained when ethanol-induced sleep was compared in ethanol-treated rats and control rats. These intriguing results challenge the generally believed concept that tolerance and cross-tolerance, once produced, are sustained with chronic treatment, and may raise the possibility that such processes are reversible even during chronic treatment, at least under certain regimens.
成年雄性Wistar大鼠喂食营养充足的液体饲料，其中乙醇提供总热量的35%，而配对喂食的对照组接受相应的饲料，其中乙醇被等热量浓度的蔗糖替代。在慢性乙醇处理2、4、6、8、10和14周后，将不同组的大鼠分别注射测试剂量的乙醇（3 g/kg）或戊巴比妥（40 mg/kg）。在注射前以及注射后30、60、90和120分钟测定直肠温度。在乙醇处理的大鼠中，在2周和4周时，测试剂量的乙醇或戊巴比妥注射后直肠温度的下降明显低于配对喂食的对照组。在慢性乙醇处理6周和8周后，相同测试剂量注射后乙醇处理大鼠的体温下降仍低于对照组。然而，在10周和14周时，两组的体温下降几乎相同。当比较乙醇处理大鼠和对照大鼠中乙醇诱导的睡眠时，获得了类似的结果模式。这些有趣的结果挑战了普遍认为的一旦产生耐受性和交叉耐受性，就会在慢性治疗中持续存在的概念，并可能增加这样的可能性，即即使在慢性治疗期间，至少在某些方案下，这些过程也是可逆的。
