Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people
Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people
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DOI：
10.1001/archpsyc.65.4.466
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发表时间：
2008-04-01
影响因子：
--
通讯作者：
Voronin, Konstantin
中科院分区：
文献类型：
--
作者：
Myrick, Hugh;Anton, Rayinond F.;Voronin, Konstantin
背景：目前治疗酒精中毒的药物并不是特别有效。神经成像技术可以预测哪些药物对治疗酒精依赖有用。目的：探讨纳曲酮、盐酸昂丹司琼或联合用药对提示性渴望和腹侧纹状体激活的影响。设计：在酒精提示时进行脑功能成像。设定：参与者是根据媒体广告从普通社区中招募的。实验程序在一家大型培训医院和医学研究所的磁共振成像套件中进行。患者：90名非寻求治疗的酒精依赖者（根据DSM-IV标准）和17名社交饮酒者（每周饮酒< 14次），通过学术中心的广告招募有偿志愿者。干预措施：在7天的双盲随机分配每日服用50毫克纳曲酮（n=23）、0.50毫克盐酸昂丹司琼（n=23）、两种药物联合服用（n= 20）或匹配的安慰剂（n= 24）后，向志愿者提供酒精的味道和一系列与酒精相关的图片、中性饮料图片和视觉对照图像。主要结果测量：观察酒精图片与中性饮料图片时脑血氧水平依赖磁共振的差异，特别关注不同药物组腹侧纹状体活动的比较。对酒精渴望的自我评价。结果：综合治疗可减少对酒精的渴望。纳曲酮加（P = 0.02）或不加（P = 0.049）昂丹司琼可降低酒精诱导的腹侧纹状体激活。在整体分析中，昂丹司琼与纳曲酮及其联合用药相似，但在区域特异性分析中处于中间水平。结论：与纳曲酮和昂丹司琼均能减少酒精刺激下腹侧纹状体多巴胺输出的动物数据一致，本研究发现证据表明，这些药物单独或联合使用均能减少酒精诱导的腹侧纹状体激活，这与它们假定的治疗效果一致。
Context: Medication for the treatment of alcoholism is currently not particularly robust. Neuroimaging techniques might predict which medications could be useful in the treatment of alcohol dependence.Objective: To explore the effect of naltrexone, ondansetron hydrochloride, or the combination of these medications on cue-induced craving and ventral striatum activation.Design: Functional brain imaging was conducted during alcohol cue presentation.Setting: Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the magnetic resonance imaging suite of a major training hospital and medical research institute.Patients: Ninety non-treatment-seeking alcohol-dependent (by DSM-IV criteria) and 17 social drinking (< 14 drinks per week) paid volunteers recruited through advertisements at an academic center.Interventions: A taste of alcohol and a series of alcohol-related pictures, neutral beverage pictures, and visual control images were provided to volunteers after 7 days of double-blind randomly assigned daily dosing with 50 mg of naltrexone (n=23), 0.50 mg of ondansetron hydrochloride (n = 23), the combination of the 2 medications (n = 20), or matching placebos (n = 24).Main Outcome Measures: Difference in brain blood oxygen level-dependent magnetic resonance when viewing alcohol pictures vs neutral beverage pictures with a particular focus on ventral striatum activity comparison across medication groups. Self-ratings of alcohol craving.Results: The combination treatment decreased craving for alcohol. Naltrexone with (P = .02) or without (P = .049) ondansetron decreased alcohol cue-induced activation of the ventral striatum. Ondansetron by itself was similar to naltrexone and the combination in the overall analysis but intermediate in a region-specific analysis.Conclusions: Consistent with animal data that suggest that both naltrexone and ondansetron reduce alcohol-stimulated dopamine output in the ventral striatum, the current study found evidence that these medications, alone or in combination, could decrease alcohol cue-induced activation of the ventral striatum, consistent with their putative treatment efficacy.