Collins A C, Wilkins L H, Slobe B S, Cao J Z, Bullock A E
Institute for Behavioral Genetics, University of Colorado, Boulder 80309-0447, USA.
Alcohol Clin Exp Res. 1996 Sep;20(6):990-9. doi: 10.1111/j.1530-0277.1996.tb01936.x.
Several previous studies have shown that 1 to 2 weeks of treatment with ethanol elicits tolerance to several effects produced by ethanol and cross-tolerance to nicotine-induced hypothermia. Similarly, short-term, high-dose nicotine treatment produces tolerance to nicotine and cross-tolerance to ethanol-induced hypothermia. In the studies reported here, C57BL/6 mice were force-fed ethanol, nicotine, or an ethanol/nicotine combination in the drinking water for 6 months. All of the chronic drug-treated mice developed tolerance to ethanol as measured by open-field activity, body temperature, and sleep-time tests. Ethanol tolerance is due, in part, to enhanced metabolism and reduced CNS sensitivity in the two ethanol-treated groups but only to reduced CNS sensitivity in the nicotine-treated group. Similar levels of tolerance to nicotine developed in those two groups that were nicotine-treated, but no tolerance to nicotine was seen in those animals treated with ethanol alone. The tolerance to nicotine may be related to an upregulation of brain (cortex, hippocampus, and hypothalamus) [3H]-nicotine binding, but ethanol tolerance is not readily explained by changes in the number of the brain high affinity nicotine binding sites.
此前的多项研究表明，用乙醇进行1至2周的治疗会引发对乙醇产生的多种效应的耐受性以及对尼古丁诱导的体温过低的交叉耐受性。同样，短期、高剂量的尼古丁治疗会产生对尼古丁的耐受性以及对乙醇诱导的体温过低的交叉耐受性。在本文报道的研究中，C57BL/6小鼠在饮用水中被强制喂食乙醇、尼古丁或乙醇/尼古丁组合，持续6个月。通过旷场活动、体温和睡眠时间测试发现，所有经慢性药物治疗的小鼠都对乙醇产生了耐受性。乙醇耐受性部分归因于两个乙醇治疗组中代谢增强和中枢神经系统敏感性降低，但在尼古丁治疗组中仅归因于中枢神经系统敏感性降低。在接受尼古丁治疗的两组中，对尼古丁产生了相似程度的耐受性，但在仅接受乙醇治疗的动物中未观察到对尼古丁的耐受性。对尼古丁的耐受性可能与脑（皮质、海马体和下丘脑）[3H] - 尼古丁结合的上调有关，但乙醇耐受性不能通过脑高亲和力尼古丁结合位点数量的变化轻易解释。
