Collins A C, Miner L L, Marks M J
Institute for Behavioral Genetics, University of Colorado, Boulder 80309.
Pharmacol Biochem Behav. 1988 May;30(1):269-78. doi: 10.1016/0091-3057(88)90455-8.
Nineteen inbred mouse strains were tested for their relative sensitivity to nicotine's effects on respiratory rate, acoustic startle response, heart rate, Y-maze activity (crosses and rears) and body temperature. Separate animals were tested for their sensitivity to nicotine-induced seizures following IP injection or IV infusion. Dose-response curves were constructed for each measure. Large strain differences were obtained for all of these measures. Nicotine's effects on heart rate, Y-maze activity and body temperature segregated together into the various mouse strains whereas seizure sensitivity segregated independently which suggests that these responses are under separate genetic control. Evidence was obtained which suggests that nicotine-induced seizures are regulated, in part, by the number of hippocampal nicotinic receptors measured with alpha-bungarotoxin (BTX). Strain differences in the development of tolerance to nicotine were also observed. Four mouse strains were tested and one of these strains (C3H) did not exhibit tolerance to nicotine. The binding of (3H)nicotine and (125I)BTX increased in the brains of all four mouse strains. These changes may relate to tolerance in some mouse strains, but since C3H mice did not exhibit tolerance even though brain nicotinic receptors changed following chronic treatment, other explanations for the role of receptor changes in tolerance to nicotine must be sought.
对19种近交系小鼠品系进行了测试，以考察它们对尼古丁影响呼吸频率、听觉惊跳反应、心率、Y迷宫活动（穿越和直立）及体温的相对敏感性。分别对动物进行腹腔注射或静脉输注尼古丁后诱发癫痫的敏感性测试。针对每一项指标构建剂量反应曲线。所有这些指标均获得了较大的品系差异。尼古丁对心率、Y迷宫活动和体温的影响在不同小鼠品系中呈现共同变化趋势，而癫痫敏感性则独立变化，这表明这些反应受不同的基因控制。有证据表明，尼古丁诱发的癫痫部分受用α-银环蛇毒素（BTX）测定的海马烟碱型受体数量的调节。还观察到了小鼠对尼古丁耐受性发展的品系差异。对四种小鼠品系进行了测试，其中一种品系（C3H）对尼古丁不表现出耐受性。所有四种小鼠品系大脑中（3H）尼古丁和（125I）BTX的结合均增加。这些变化可能与某些小鼠品系的耐受性有关，但由于C3H小鼠即使在长期处理后大脑烟碱型受体发生变化的情况下仍不表现出耐受性，因此必须寻找受体变化在尼古丁耐受性中作用的其他解释。
