阿片类药物戒断后动机和学习的改变:奖赏处理长期失调的证据。

Altered motivation and learning following opiate withdrawal: evidence for prolonged dysregulation of reward processing.

作者信息

Harris Glenda C, Aston-Jones Gary

机构信息

Department of Psychiatry, University of Pennsylvania, 705 Stellar Chance/6100, Philadelphia, PA 19104, USA.

出版信息

Neuropsychopharmacology. 2003 May;28(5):865-71. doi: 10.1038/sj.npp.1300122. Epub 2003 Mar 12.

Abstract

Opiate abuse has been associated with cognitive deficits in human addicts. To determine if prior opiate exposure alters the ability to learn, we trained animals in an instrumental learning task for a food reward. During a 2-week period after withdrawal, morphine-abstinent rats were significantly slower at learning an escalating fixed-ratio response for food reward compared to placebo-treated animals. When these same animals were trained in a conditioned suppression paradigm (two tone-shock pairings given in the operant box), the morphine-withdrawn animals showed greater retention by taking significantly longer to resume responding for food reward when the tone was presented. In a third experiment, morphine-abstinent rats withdrawn 2 or 5 weeks were tested for their ability to associate a highly palatable food reward with a specific environment using a place-conditioning paradigm. At 2 weeks postwithdrawal, morphine-abstinent rats did not show any significant place preference for a food they readily consumed, while placebo-treated rats readily learned to prefer the food-paired environment. At 5 weeks postwithdrawal, rats developed significantly less preference for food-associated cues, but more preference for morphine-associated cues, compared to placebo-treated animals. These data suggest that prior morphine exposure may have prolonged effects on the motivation for natural rewards, which in turn may compromise the ability of former addicts to overcome their addictions.

摘要

阿片类药物滥用与人类成瘾者的认知缺陷有关。为了确定先前的阿片类药物暴露是否会改变学习能力,我们让动物在一项以食物奖励为目的的工具性学习任务中进行训练。在戒断后的2周内,与接受安慰剂治疗的动物相比,吗啡戒断的大鼠在学习逐步增加的固定比率食物奖励反应时明显更慢。当这些相同的动物在条件性抑制范式(在操作箱中给予两次音调-电击配对)中进行训练时,吗啡戒断的动物表现出更强的记忆保持能力,即当呈现音调时,它们恢复对食物奖励反应的时间明显更长。在第三个实验中,使用位置条件范式测试了戒断2周或5周的吗啡戒断大鼠将高度可口的食物奖励与特定环境联系起来的能力。在戒断后2周时,吗啡戒断的大鼠对它们容易食用的食物没有表现出任何明显的位置偏好,而接受安慰剂治疗的大鼠很容易学会偏好与食物配对的环境。与接受安慰剂治疗的动物相比,在戒断后5周时,大鼠对与食物相关线索的偏好明显降低,但对与吗啡相关线索的偏好增加。这些数据表明,先前的吗啡暴露可能对自然奖励的动机产生长期影响,这反过来可能损害前成瘾者克服成瘾的能力。

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