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评估一种拟用于大鼠复吸研究的“三标准”可卡因成瘾模型。

Assessment of a proposed "three-criteria" cocaine addiction model for use in reinstatement studies with rats.

作者信息

Waters R Parrish, Moorman David E, Young Amy B, Feltenstein Matthew W, See Ronald E

机构信息

NeuroCure Cluster of Excellence, Charité Universitätsmedizin, Charité Platz 1, 10117, Berlin, Germany,

出版信息

Psychopharmacology (Berl). 2014 Aug;231(16):3197-205. doi: 10.1007/s00213-014-3497-2. Epub 2014 Mar 11.

Abstract

RATIONALE

Relapse is a primary obstacle in the treatment of addiction disorders, and as such, understanding this phenomenon is a major effort of clinical and preclinical studies of cocaine addiction.

OBJECTIVE

A recently developed protocol uses laboratory rats to model cocaine addiction by examining three criteria of addiction-like behaviors (persistent seeking in the absence of drug, high motivation for drug, and resistance to punishment during drug seeking) to detect subjects that possess an addiction phenotype. We closely followed this protocol in order to detect rats possessing this addiction phenotype, with the goal of utilizing this model in future studies investigating potential therapies for relapse in human cocaine addicts.

RESULTS

The majority of the rats used in this study exhibited multiple characteristics thought to be associated with addiction-like behavior in rats, including robust reinstatement to multiple stimuli and high motivation to obtain cocaine. However, no rats displayed the complete addiction phenotype as previously described, due to a complete lack of addiction-like behavior in all subjects on two of the three addiction criteria (drug seeking in the absence of drug and resistance to punishment).

CONCLUSIONS

Our data highlight the independence of behavioral aspects of a rat addiction-like phenotype and suggest that some of these behavioral criteria may be altogether absent in some rat populations. Furthermore, our results suggest a closer review and analysis of some parameters used in this protocol and its global utility.

摘要

原理

复发是成瘾性疾病治疗中的主要障碍,因此,了解这一现象是可卡因成瘾临床和临床前研究的主要工作。

目的

最近开发的一项方案通过检测成瘾样行为的三个标准(在无药物情况下持续寻求、对药物的高动机以及在寻求药物期间对惩罚的抵抗),利用实验室大鼠对可卡因成瘾进行建模,以检测具有成瘾表型的个体。我们严格遵循该方案以检测具有这种成瘾表型的大鼠,目标是在未来研究中利用该模型调查人类可卡因成瘾者复发的潜在治疗方法。

结果

本研究中使用的大多数大鼠表现出多种被认为与大鼠成瘾样行为相关的特征,包括对多种刺激的强烈恢复以及获取可卡因的高动机。然而,由于在三个成瘾标准中的两个标准(无药物时寻求药物和对惩罚的抵抗)上所有个体完全缺乏成瘾样行为,没有大鼠表现出如先前描述的完整成瘾表型。

结论

我们的数据突出了大鼠成瘾样表型行为方面的独立性,并表明在某些大鼠群体中可能完全不存在某些行为标准。此外,我们的结果表明需要对该方案中使用的一些参数及其整体效用进行更仔细的审查和分析。

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