双硫仑对啮齿类动物赌博任务中选择行为的影响：与儿茶酚胺水平的关系。
Effects of disulfiram on choice behavior in a rodent gambling task: association with catecholamine levels.
机构信息
Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, University of Toronto, 33 Russell Street, Toronto, M5S 2S1, Canada.
Department of Human Genetics, Emory University School of Medicine, Whitehead 301, 615 Michael St, Atlanta, GA, 30322, USA.
出版信息
Psychopharmacology (Berl). 2018 Jan;235(1):23-35. doi: 10.1007/s00213-017-4744-0. Epub 2017 Oct 30.
RATIONALE
Gambling disorder is a growing societal concern, as recognized by its recent classification as an addictive disorder in the DSM-5. Case reports have shown that disulfiram reduces gambling-related behavior in humans.
OBJECTIVES
The purpose of the present study was to determine whether disulfiram affects performance on a rat gambling task, a rodent version of the Iowa gambling task in humans, and whether any changes were associated with alterations in dopamine and/or norepinephrine levels.
METHODS
Rats were administered disulfiram prior to testing on the rat gambling task or prior to analysis of dopamine or norepinephrine levels in brain homogenates. Rats in the behavioral task were divided into two subgroups (optimal vs suboptimal) based on their baseline levels of performance in the rat gambling task. Rats in the optimal group chose the advantageous strategy more, and rats in the suboptimal group (a parallel to problem gambling) chose the disadvantageous strategy more. Rats were not divided into optimal or suboptimal groups prior to neurochemical analysis.
RESULTS
Disulfiram administered 2 h, but not 30 min, before the task dose-dependently improved choice behavior in the rats with an initial disadvantageous "gambling-like" strategy, while having no effect on the rats employing an advantageous strategy. The behavioral effects of disulfiram were associated with increased striatal dopamine and decreased striatal norepinephrine.
CONCLUSIONS
These findings suggest that combined actions on dopamine and norepinephrine may be a useful treatment for gambling disorders.
原理
赌博障碍是一个日益严重的社会问题，正如其在 DSM-5 中被新近归类为成瘾障碍所认可。病例报告表明，双硫仑可减少人类的赌博相关行为。
目的
本研究旨在确定双硫仑是否会影响大鼠赌博任务的表现，这是人类 Iowa 赌博任务的啮齿动物版本，以及任何变化是否与多巴胺和/或去甲肾上腺素水平的改变有关。
方法
在大鼠赌博任务测试前或脑匀浆中多巴胺或去甲肾上腺素水平分析前，给予大鼠双硫仑。在行为任务中，根据大鼠在大鼠赌博任务中的基线表现，将大鼠分为两组（最优组与次优组）。最优组大鼠选择有利策略的次数更多，而次优组（类似于赌博问题）大鼠选择不利策略的次数更多。在神经化学分析之前，大鼠未分为最优或次优组。
结果
双硫仑在任务前 2 小时给予，但不在 30 分钟前给予，可剂量依赖性地改善初始不利“赌博样”策略的大鼠的选择行为，而对采用有利策略的大鼠则没有影响。双硫仑的行为效应与纹状体多巴胺增加和纹状体去甲肾上腺素减少有关。
结论
这些发现表明，多巴胺和去甲肾上腺素的联合作用可能是治疗赌博障碍的一种有效方法。
Zotero 插件