DECREASED BRAIN REWARD PRODUCED BY ETHANOL WITHDRAWAL
DECREASED BRAIN REWARD PRODUCED BY ETHANOL WITHDRAWAL
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DOI：
10.1073/pnas.92.13.5880
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发表时间：
1995-06-20
影响因子：
11.1
通讯作者：
KOOB, GF
中科院分区：
文献类型：
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作者：
SCHULTEIS, G;MARKOU, A;KOOB, GF
长期戒断各种药物的滥用，如乙醇、阿片类药物和精神兴奋剂，会导致戒断综合征，这在很大程度上是每个药物类别所特有的。然而，在人类中，这些戒断综合症的一个共同症状是消极的情感/动机状态。先前在啮齿动物身上的研究表明，颅内自我刺激（ICSS）奖励阈值的升高提供了一个定量指标，作为从精神兴奋剂和阿片类药物戒断期间消极情感状态的模型。目前的研究试图确定ICSS阈值升高是否也伴随慢性乙醇暴露的戒断，足以诱导身体依赖。在下丘脑外侧放置刺激电极的大鼠接受离散电流强度ICSS阈值程序的训练；随后，他们在乙醇蒸气室中接受慢性乙醇治疗（平均血液酒精水平为197毫克/分升）。在去除乙醇后，观察到ICSS阈值随时间的升高，而不是对照室。停止乙醇暴露后48小时阈值显著升高，6-8小时达到峰值。血液酒精浓度与阈值升高的幅度直接相关。传统的明显戒断迹象的评分显示出相似的表达和解决的时间过程。结果表明，奖励系统功能下降（奖励阈值升高）是长期服用几种不同类别滥用药物后戒断的常见因素。
Abstinence from chronic administration of various drugs of abuse such as ethanol, opiates, and psychostimulants results in withdrawal syndromes largely unique to each drug class. However, one symptom that appears common to these withdrawal syndromes in humans is a negative affective/motivational state. Prior work in rodents has shown that elevations in intracranial self-stimulation (ICSS) reward thresholds provide a quantitative index that serves as a model for the negative affective state during withdrawal from psychostimulants and opiates. The current study sought to determine whether ICSS threshold elevations also accompany abstinence from chronic ethanol exposure sufficient to induce physical dependence, Rats prepared with stimulating electrodes in the lateral hypothalamus were trained in a discretetrial current-intensity ICSS threshold procedure; subsequently they were subjected to chronic ethanol administration in ethanol vapor chambers (average blood alcohol level of 197 mg/dl). A time-dependent elevation in ICSS thresholds was observed following removal from the ethanol, but not the control, chambers. Thresholds were significantly elevated for 48 hr after cessation of ethanol exposure, with peak elevations observed at 6-8 hr. Blood alcohol levels were directly correlated with the magnitude of peak threshold elevation. Ratings of traditional overt signs of withdrawal showed a similar time course of expression and resolution. The results suggest that decreased function of reward systems (elevations in reward thresholds) is a common element of withdrawal from chronic administration of several diverse classes of abused drugs.