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对繁育出的饮用高剂量或低剂量甲基苯丙胺的小鼠的甲基苯丙胺饮用微观结构研究

Methamphetamine drinking microstructure in mice bred to drink high or low amounts of methamphetamine.

作者信息

Eastwood Emily C, Barkley-Levenson Amanda M, Phillips Tamara J

机构信息

Department of Behavioral Neuroscience and Methamphetamine Abuse Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Rd., Portland, OR 97239, USA.

Department of Behavioral Neuroscience and Methamphetamine Abuse Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Rd., Portland, OR 97239, USA; Veterans Affairs Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR 97239, USA.

出版信息

Behav Brain Res. 2014 Oct 1;272:111-20. doi: 10.1016/j.bbr.2014.06.035. Epub 2014 Jun 27.

Abstract

Genetic factors likely influence individual sensitivity to positive and negative effects of methamphetamine (MA) and risk for MA dependence. Genetic influence on MA consumption has been confirmed by selectively breeding mouse lines to consume high (MAHDR) or low (MALDR) amounts of MA, using a two-bottle choice MA drinking (MADR) procedure. Here, we employed a lickometer system to characterize the microstructure of MA (20, 40, and 80mg/l) and water intake in MAHDR and MALDR mice in 4-h limited access sessions, during the initial 4hours of the dark phase of their 12:12h light:dark cycle. Licks at one-minute intervals and total volume consumed were recorded, and bout analysis was performed. MAHDR and MALDR mice consumed similar amounts of MA in mg/kg on the first day of access, but MAHDR mice consumed significantly more MA than MALDR mice during all subsequent sessions. The higher MA intake of MAHDR mice was associated with a larger number of MA bouts, longer bout duration, shorter interbout interval, and shorter latency to the first bout. In a separate 4-h limited access MA drinking study, MALDR and MAHDR mice had similar blood MA levels on the first day MA was offered, but MAHDR mice had higher blood MA levels on all subsequent days, which corresponded with MA intake. These data provide insight into the microstructure of MA intake in an animal model of differential genetic risk for MA consumption, which may be pertinent to MA use patterns relevant to genetic risk for MA dependence.

摘要

遗传因素可能影响个体对甲基苯丙胺(MA)正负效应的敏感性以及MA依赖风险。通过使用双瓶选择MA饮用(MADR)程序,选择性培育出高(MAHDR)或低(MALDR)MA摄入量的小鼠品系,已证实遗传对MA消费有影响。在此,我们采用舔舐计量系统,在12:12小时光照:黑暗周期的黑暗阶段最初4小时内,对MAHDR和MALDR小鼠在4小时有限接触期内MA(20、40和80mg/l)和水摄入的微观结构进行表征。记录每隔一分钟的舔舐次数和消耗的总体积,并进行发作分析。在接触的第一天,MAHDR和MALDR小鼠以mg/kg计消耗的MA量相似,但在所有后续实验中,MAHDR小鼠消耗的MA明显多于MALDR小鼠。MAHDR小鼠较高的MA摄入量与更多的MA发作次数、更长的发作持续时间、更短的发作间隔以及首次发作的更短潜伏期相关。在另一项4小时有限接触MA饮用研究中,在提供MA的第一天,MALDR和MAHDR小鼠的血液MA水平相似,但在所有后续日子里,MAHDR小鼠的血液MA水平更高,这与MA摄入量相对应。这些数据为MA消费差异遗传风险动物模型中MA摄入的微观结构提供了见解,这可能与MA依赖遗传风险相关的MA使用模式有关。

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