Schulteis G, Markou A, Cole M, Koob G F
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):5880-4. doi: 10.1073/pnas.92.13.5880.
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 discrete-trial 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.
戒除长期使用的各种成瘾药物，如乙醇、阿片类药物和精神兴奋剂，会导致很大程度上因药物种类而异的戒断综合征。然而，人类这些戒断综合征中似乎共有的一个症状是消极的情感/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）奖赏阈值的升高提供了一个定量指标，可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。本研究旨在确定ICSS阈值升高是否也伴随足以诱导身体依赖的慢性乙醇暴露的戒除。将在下丘脑外侧植入刺激电极的大鼠在离散试验电流强度ICSS阈值程序中进行训练；随后，将它们置于乙醇蒸汽室中进行慢性乙醇给药（平均血液酒精水平为197mg/dl）。从乙醇室（而非对照室）取出后，观察到ICSS阈值随时间升高。乙醇暴露停止后48小时内阈值显著升高，在6 - 8小时达到峰值升高。血液酒精水平与峰值阈值升高幅度直接相关。传统戒断明显体征的评分显示出类似的表达和消退时间进程。结果表明，奖赏系统功能下降（奖赏阈值升高）是多种不同类型成瘾药物长期使用后戒断的一个共同因素。
