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高冲动性与低冲动性大鼠中可卡因、咖啡因及应激诱发的可卡因复吸:孕烷醇酮的治疗作用

Cocaine-, caffeine-, and stress-evoked cocaine reinstatement in high vs. low impulsive rats: treatment with allopregnanolone.

作者信息

Regier Paul S, Claxton Alexander B, Zlebnik Natalie E, Carroll Marilyn E

机构信息

Graduate Program in Neuroscience, University of Minnesota, Minneapolis, MN 55455, United States.

Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455, United States.

出版信息

Drug Alcohol Depend. 2014 Oct 1;143:58-64. doi: 10.1016/j.drugalcdep.2014.07.001. Epub 2014 Jul 11.

Abstract

BACKGROUND

Previous research indicates that individual differences in traits such as impulsivity, avidity for sweets, and novelty reactivity are predictors of several aspects of drug addiction. Specifically, rats that rank high on these behavioral measures are more likely than their low drug-seeking counterparts to exhibit several characteristics of drug-seeking behavior. In contrast, initial work suggests that the low drug-seeking animals are more reactive to negative events (e.g., punishment and anxiogenic stimuli). The goal of this study was to compare high and low impulsive rats on reinstatement of cocaine-seeking behavior elicited by cocaine (COC) and by negative stimuli such as the stress-inducing agent yohimbine (YOH) or a high dose of caffeine (CAFF). An additional goal was to determine whether treatment with allopregnanolone (ALLO) would reduce reinstatement (or relapse) of cocaine-seeking behavior under these priming conditions.

METHODS

Female rats were selected as high (HiI) or low (LoI) impulsive using a delay-discounting task. After selection, they were allowed to self-administer cocaine for 12 days. Cocaine was then replaced with saline, and rats extinguished lever responding over 16 days. Subsequently, rats were pretreated with either vehicle control or ALLO, and cocaine seeking was reinstated by injections of COC, CAFF, or YOH.

RESULTS

While there were no phenotype differences in maintenance and extinction of cocaine self-administration or reinstatement under control treatment conditions, ALLO attenuated COC- and CAFF-primed reinstatement in LoI but not HiI rats.

CONCLUSIONS

Overall, the present findings suggest that individual differences in impulsive behavior may influence efficacy of interventions aimed to reduce drug-seeking behavior.

摘要

背景

先前的研究表明,冲动性、对甜食的喜好以及对新事物反应性等特质的个体差异是药物成瘾多个方面的预测指标。具体而言,在这些行为指标上得分高的大鼠比那些药物寻求行为少的同类更有可能表现出药物寻求行为的若干特征。相比之下,初步研究表明,药物寻求行为少的动物对负面事件(如惩罚和致焦虑刺激)反应更强。本研究的目的是比较高冲动性和低冲动性大鼠在由可卡因(COC)以及诸如应激诱导剂育亨宾(YOH)或高剂量咖啡因(CAFF)等负面刺激引发的可卡因寻求行为恢复方面的差异。另一个目的是确定在这些启动条件下,用别孕烯醇酮(ALLO)治疗是否会减少可卡因寻求行为的恢复(或复发)。

方法

使用延迟折扣任务将雌性大鼠选为高冲动性(HiI)或低冲动性(LoI)。选好后,让它们自我给药可卡因12天。然后用生理盐水替代可卡因,大鼠在16天内消退杠杆反应。随后,大鼠接受载体对照或ALLO预处理,通过注射COC、CAFF或YOH来恢复可卡因寻求行为。

结果

在对照治疗条件下,可卡因自我给药的维持、消退或恢复方面没有表型差异,但ALLO减弱了LoI大鼠而非HiI大鼠中由COC和CAFF引发的恢复。

结论

总体而言,目前的研究结果表明,冲动行为的个体差异可能会影响旨在减少药物寻求行为的干预措施的效果。

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