Selective breeding for magnitude of methamphetamine-induced sensitization alters methamphetamine consumption.
Selective breeding for magnitude of methamphetamine-induced sensitization alters methamphetamine consumption.
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DOI：
10.1007/s00213-010-2086-2
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发表时间：
2011-04
影响因子：
3.4
通讯作者：
Phillips, Tamara J.
中科院分区：
文献类型：
--
作者：
Scibelli, Angela C.;McKinnon, Carrie S.;Reed, Cheryl;Burkhart-Kasch, Sue;Li, Na;Baba, Harue;Wheeler, Jeanna M.;Phillips, Tamara J.
关键词：
基因决定的对药物致敏敏感性的差异可能与药物消费的风险有关。为了确定是否可以使用选择性育种来建立对甲基苯丙胺(MA)具有不同程度的运动敏感度的小鼠品系，进行了研究。还检测了MA敏化(MASENS)系对MA的遗传相关反应。以C57BL/6J和DBA/2J品系杂交F2代小鼠为实验材料，按致敏程度饲养小鼠，测定小鼠对1 mg/kg MA重复注射的运动敏感度。对五个选定的后代世代进行了测试。所有几代人都被测试了MA的摄入量，其中一些人被测试了对MA的剂量依赖的运动刺激反应，糖精、奎宁和氯化钾的摄入量作为味觉敏感度的衡量标准，以及急性和重复MA后MA的清除。选择育种产生了两个品系[MA高敏化(MAHSENS)和MA低敏化(MALSENS)]，它们的MA诱导敏化程度不同。最初，在选择过程中，MAHSENS小鼠摄入更多MA的情况发生逆转，因此MALSENS小鼠摄入更多MA。MAHSENS小鼠对MA的急性刺激作用表现出更高的敏感性，但不同品系之间在MA从血液中的清除方面没有显著差异。遗传因素影响MA诱导的运动敏化的大小，参与该反应大小的一些基因也影响MA的敏感性和消耗。导致MA诱导的更大敏感度的遗传因素可能对高水平的MA消费起到保护作用。
Genetically determined differences in susceptibility to drug-induced sensitization could be related to risk for drug consumption. Studies were performed to determine whether selective breeding could be used to create lines of mice with different magnitudes of locomotor sensitization to methamphetamine (MA). MA sensitization (MASENS) lines were also examined for genetically correlated responses to MA. Beginning with the F2 cross of C57BL/6J and DBA/2J strains, mice were tested for locomotor sensitization to repeated injections of 1 mg/kg MA and bred based on magnitude of sensitization. Five selected offspring generations were tested. All generations were also tested for MA consumption, and some were tested for dose-dependent locomotor-stimulant responses to MA, consumption of saccharin, quinine, and potassium chloride as a measure of taste sensitivity, and MA clearance after acute and repeated MA. Selective breeding resulted in creation of two lines [MA high sensitization (MAHSENS) and MA low sensitization (MALSENS)] that differed in magnitude of MA-induced sensitization. Initially, greater MA consumption in MAHSENS mice reversed over the course of selection so that MALSENS mice consumed more MA. MAHSENS mice exhibited greater sensitivity to the acute stimulant effects of MA, but there were no significant differences between the lines in MA clearance from blood. Genetic factors influence magnitude of MA-induced locomotor sensitization and some of the genes involved in magnitude of this response also influence MA sensitivity and consumption. Genetic factors leading to greater MA-induced sensitization may serve a protective role against high levels of MA consumption.
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DOI：
10.1097/00000374-200006000-00007
发表时间：
2000-06-01
影响因子：
3.2
作者：
Holdstock, L;King, AC;de Wit, H
通讯作者：
de Wit, H
影响因子：
5.6
作者：
Ferrario, Carrie R.;Robinson, Terry E.
通讯作者：
Robinson, Terry E.
影响因子：
--
作者：
Boileau, Isabelle;Dagher, Alain;Benkelfat, Chawki
通讯作者：
Benkelfat, Chawki
影响因子：
2.7
作者：
Flagel, Shelly B.;Watson, Stanley J.;Robinson, Terry E.
通讯作者：
Robinson, Terry E.
影响因子：
10.6
作者：
Ferrario, CR;Gorny, G;Robinson, TE
通讯作者：
Robinson, TE