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评估纳曲酮对大鼠赌博任务的影响,以测试其对赌博障碍的预测效度。

Evaluating the Impact of Naltrexone on the Rat Gambling Task to Test Its Predictive Validity for Gambling Disorder.

作者信息

Di Ciano Patricia, Le Foll Bernard

机构信息

Translational Addiction Research Laboratory, CAMH, Toronto, Canada.

Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada.

出版信息

PLoS One. 2016 May 18;11(5):e0155604. doi: 10.1371/journal.pone.0155604. eCollection 2016.

Abstract

Gambling Disorder has serious consequences and no medications are currently approved for the treatment of this disorder. One factor that may make medication development difficult is the lack of animal models of gambling that would allow for the pre-clinical screening of efficacy. Despite this, there is evidence from clinical trials that opiate antagonists, in particular naltrexone, may be useful in treating gambling disorder. To-date, the effects of naltrexone on pre-clinical models of gambling have not been evaluated. The purpose of the present study was to evaluate the effects of naltrexone in an animal model of gambling, the rat gambling task (rGT), to determine whether this model has some predictive validity. The rGT is a model in which rats are given a choice of making either a response that produces a large reward or a small reward. The larger the reward, the greater the punishment, and thus this task requires that the animal inhibit the 'tempting' choice, as the smaller reward option produces overall the most number of rewards per session. People with gambling disorder chose the tempting option more, thus the rGT may provide a model of problem gambling. It was found that naltrexone improved performance on this task in a subset of animals that chose the 'tempting', disadvantageous choice, more at baseline. Thus, the results of this study suggest that the rGT should be further investigated as a pre-clinical model of gambling disorder and that further investigation into whether opioid antagonists are effective in treating Gambling Disorder may be warranted.

摘要

赌博障碍有严重后果,目前尚无药物被批准用于治疗该障碍。可能使药物研发困难的一个因素是缺乏赌博动物模型,而这种模型可用于临床前疗效筛选。尽管如此,临床试验有证据表明阿片类拮抗剂,尤其是纳曲酮,可能对治疗赌博障碍有用。迄今为止,纳曲酮对赌博临床前模型的作用尚未得到评估。本研究的目的是评估纳曲酮在一种赌博动物模型——大鼠赌博任务(rGT)中的作用,以确定该模型是否具有一定的预测效度。rGT是一种模型,在该模型中,大鼠可选择做出能产生大奖励或小奖励的反应。奖励越大,惩罚越大,因此该任务要求动物抑制“诱人”的选择,因为较小奖励选项总体上每次试验能产生最多奖励。患有赌博障碍的人更多地选择诱人选项,因此rGT可能提供了一个问题赌博模型。研究发现,纳曲酮在一部分基线时更多选择“诱人”的不利选项的动物中改善了该任务的表现。因此,本研究结果表明,rGT作为赌博障碍的临床前模型应进一步研究,并且可能有必要进一步研究阿片类拮抗剂治疗赌博障碍是否有效。

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