Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
Drug Alcohol Depend. 2019 Jul 1;200:181-190. doi: 10.1016/j.drugalcdep.2019.02.028. Epub 2019 May 9.
Despite known genetic variation across races, studies examining pharmacogenetics of a single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1) on clinical response to naltrexone have been conducted in predominantly Caucasian samples. Evidence is mixed for pharmacogenetic OPRM1 and naltrexone effects on neural responses to alcohol cues. The current study tests the pharmacogenetic effects of naltrexone and OPRM1 on neural responses to alcohol taste cues in heavy drinkers of East Asian descent.
Participants (N = 41) completed two double-blinded and counterbalanced functional magnetic resonance imaging (fMRI) sessions: one after taking naltrexone (50 mg/day) for four days and one after taking placebo for four days. Following titration, participants completed an fMRI alcohol taste-cues task. Analyses tested effects of naltrexone, OPRM1, and their interaction in whole-brain and region of interest (ROI) analyses of functional activation and functional connectivity in response to alcohol versus water taste cues.
We found no effects of naltrexone orOPRM1 on neural activation in whole-brain and ROI analyses, which included left and right ventral striatum (VS), anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). Naltrexone increased functional connectivity between left VS and clusters in medial prefrontal cortex, posterior cingulate gyrus, as well as right VS and occipital cortex, compared to placebo.
Naltrexone treatment enhanced functional connectivity in a key reinforcement-related pathway during alcohol versus water taste cues, corroborating neuroimaging work with other substances. Null medication and pharmacogenetics effects on functional activation add to a mixed naltrexone literature and may underscore the modest size of these effects in East Asians.
尽管在不同种族之间存在已知的遗传变异，但对阿片受体基因（OPRM1）单一核苷酸多态性（SNP）的药物遗传学研究在主要是高加索人群样本中进行。药物遗传学 OPRM1 和纳曲酮对酒精线索的神经反应的影响的证据存在分歧。本研究测试了纳曲酮和 OPRM1 对东亚裔重度饮酒者对酒精味觉线索的神经反应的药物遗传学效应。
参与者（N=41）完成了两个双盲和对照的功能磁共振成像（fMRI）会话：一个在服用纳曲酮（50mg/天）四天后，一个在服用安慰剂四天后。滴定后，参与者完成了 fMRI 酒精味觉线索任务。分析测试了纳曲酮、OPRM1 及其相互作用对酒精与水味觉线索反应的全脑和感兴趣区（ROI）分析中的功能激活和功能连接的影响。
我们没有发现纳曲酮或 OPRM1 对全脑和 ROI 分析中的神经激活有影响，包括左、右腹侧纹状体（VS）、前扣带回皮质（ACC）和眶额皮质（OFC）。与安慰剂相比，纳曲酮增加了左 VS 与内侧前额叶皮质、后扣带回、右 VS 与枕叶皮质之间的功能连接。
纳曲酮治疗增强了酒精与水味觉线索反应期间关键强化相关通路的功能连接，与其他物质的神经影像学工作相吻合。药物和药物遗传学对功能激活的影响为纳曲酮的文献增加了混合效应，并且可能强调了这些效应在东亚人中的适度大小。
