Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, United States.
Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, United States.
Brain Res Bull. 2018 Apr;138:73-79. doi: 10.1016/j.brainresbull.2017.09.008. Epub 2017 Sep 20.
The single nucleotide polymorphism of the μ-opioid receptor, OPRM1 A118G, has been associated with greater drug and alcohol use, increased sensitivity to pain, and reduced sensitivity to the antinociceptive effects of opiates. In the present studies, we employed a 'humanized' mouse model containing the wild-type (118AA) or variant (118GG) allele to examine behavior in a model of heroin-induced devaluation of an otherwise palatable saccharin cue when repeated saccharin-heroin pairings occurred every 24h (Experiment 1) or every 48h (Experiment 2). The results showed that, while both the 118AA and 118GG mice demonstrated robust avoidance of the heroin-paired saccharin cue following daily taste-drug pairings, only the 118AA mice suppressed intake of the heroin-paired saccharin cue when 48h elapsed between each taste-drug pairing. Humanized 118GG mice, then, defend their intake of the sweet cue despite saccharin-heroin pairings and this effect is illuminated by the use of spaced, rather than massed, trials. Given that this pattern of strain difference is not evident with saccharin-cocaine pairings (Freet et al., 2015), reduced avoidance of the heroin-paired saccharin cue by the 118GG mice may be due to an interaction between the opiate and the subjects' drive for the sweet or, alternatively, to differential downstream sensitivity to the aversive kappa mediated properties of the drug. These alternative hypotheses are addressed.
μ-阿片受体的单核苷酸多态性，OPRM1 A118G，与更大的药物和酒精使用，增加对疼痛的敏感性，并降低对阿片类药物的镇痛效果的敏感性有关。在本研究中，我们采用了含有野生型（118AA）或变异型（118GG）等位基因的“人源化”小鼠模型，当重复的蔗糖-海洛因配对每 24 小时发生一次（实验 1）或每 48 小时发生一次（实验 2）时，检查海洛因诱导的蔗糖线索价值降低模型中的行为。结果表明，虽然 118AA 和 118GG 小鼠在每天进行味觉-药物配对后都强烈避免了与海洛因配对的蔗糖线索，但只有 118AA 小鼠在每两次味觉-药物配对之间间隔 48 小时时才抑制了与海洛因配对的蔗糖线索的摄入量。然后，人源化 118GG 小鼠尽管进行了蔗糖-海洛因配对，但仍能保护自己对甜味线索的摄入，而这一效应是通过使用间隔而非密集的试验来阐明的。鉴于这种品系差异的模式在蔗糖-可卡因配对中并不明显（Freet 等人，2015 年），118GG 小鼠对与海洛因配对的蔗糖线索的回避减少可能是由于阿片类药物与受试者对甜味的驱动力之间的相互作用，或者是由于对药物的厌恶 κ 介导的特性的下游敏感性不同。这些替代假设得到了探讨。
