Department of Behavioral Neuroscience and Methamphetamine Abuse Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA.
Neuropharmacology. 2012 Jun;62(7):2169-77. doi: 10.1016/j.neuropharm.2012.01.002. Epub 2012 Jan 20.
Sensitivity to reinforcement from methamphetamine (MA) likely influences risk for MA addiction, and genetic differences are one source of individual variation. Generation of two sets of selectively bred mouse lines for high and low MA drinking has shown that genetic factors influence MA intake, and pronounced differences in sensitivity to rewarding and aversive effects of MA play a significant role. Further validation of these lines as a unique genetic model relevant to MA addiction was obtained using operant methods to study MA reinforcement. High and low MA drinking line mice were used to test the hypotheses that: 1) oral and intracerebroventricular (ICV) MA serve as behavioral reinforcers, and 2) MA exhibits greater reinforcing efficacy in high than low MA drinking mice. Operant responses resulted in access to an MA or non-MA drinking tube or intracranial delivery of MA. Behavioral activation consequent to orally consumed MA was determined. MA available for consumption maintained higher levels of reinforced instrumental responding in high than low MA drinking line mice, and MA intake in the oral operant procedure was greater in high than low MA drinking line mice. Behavioral activation was associated with amount of MA consumed during operant sessions. High line mice delivered more MA via ICV infusion than did low line mice across a range of doses. Thus, genetic risk factors play a critical role in the reinforcing efficacy of MA and the oral self-administration procedure is suitable for delineating genetic contributions to MA reinforcement.
对甲基苯丙胺（MA）的强化敏感性可能会影响 MA 成瘾的风险，而遗传差异是个体变异的一个来源。两组用于高和低 MA 饮酒的选择性繁殖小鼠系的产生表明遗传因素会影响 MA 的摄入，并且对 MA 的奖励和厌恶作用的敏感性差异很大，这起着重要作用。使用操作性方法研究 MA 强化作用，进一步验证了这些品系作为与 MA 成瘾相关的独特遗传模型的有效性。使用高 MA 和低 MA 饮酒线小鼠来检验以下假设：1）口服和脑室内（ICV）MA 作为行为增强剂，2）MA 在高 MA 饮酒小鼠中比低 MA 饮酒小鼠具有更强的增强效力。操作性反应可获得 MA 或非 MA 饮用管或 MA 的颅内递送。确定口服消耗 MA 后产生的行为激活。可消耗的 MA 可维持高 MA 和低 MA 饮酒线小鼠中更高水平的强化工具性反应，并且高 MA 和低 MA 饮酒线小鼠的口服操作性程序中的 MA 摄入量更大。行为激活与操作性会议期间消耗的 MA 量有关。高线小鼠通过 ICV 输注输送的 MA 比低线小鼠多，跨越一系列剂量。因此，遗传风险因素在 MA 的强化效力中起着关键作用，而口服自我给药程序适合阐明 MA 强化作用的遗传贡献。
