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猴子体内的神经肽与酒精成瘾

Neuropeptides and alcohol addiction in monkeys.

作者信息

van Ree J M, Kornet M, Goosen C

机构信息

Department of Pharmacology, Rudolf Magnus Institute, Utrecht University, The Netherlands.

出版信息

EXS. 1994;71:165-74. doi: 10.1007/978-3-0348-7330-7_17.

Abstract

Neuropeptides have been implicated in experimental drug addiction. Desglycinamide (Arg8) vasopressin (DGAVP) attenuates heroin and cocaine intake during initiation of drug self-administration in rats. beta-Endorphin is self-administered in rats and a role of endogenous opioids in cocaine reward has been proposed. The present studies deal with voluntary alcohol consumption in monkeys under free choice conditions. Monkeys initiated alcohol drinking within a few days and after a stable drinking pattern was acquired increased their ethanol consumption during a short period following interruption of the alcohol supply (relapse). The alcohol drinking behavior seems under the control of reinforcement principles. DGAVP reduced the acquisition of alcohol drinking in the majority of treated monkeys. Initiation of alcohol drinking induced modifications in neuroendocrine homeostasis e.g. an increased plasma beta-endorphin. Both the opioid antagonist naltrexone and the opioid agonist morphine dose-dependently decreased alcohol intake during continuous supply and after imposed abstinence. The monkeys were more sensitive to both drugs after imposed abstinence. The effects are interpreted in the context of the endorphin compensation hypothesis of addictive behavior. It is suggested that endorphins may be particularly implicated in craving for addictive drugs and in relapse of addictive behavior.

摘要

神经肽与实验性药物成瘾有关。去甘氨酰胺(精氨酸8)加压素(DGAVP)在大鼠开始药物自我给药期间可减少海洛因和可卡因的摄入量。β-内啡肽可在大鼠中自我给药,并且有人提出内源性阿片类物质在可卡因奖赏中起作用。目前的研究涉及自由选择条件下猴子的自愿饮酒情况。猴子在几天内开始饮酒,在获得稳定的饮酒模式后,在酒精供应中断后的短时间内(复发)增加了乙醇摄入量。饮酒行为似乎受强化原则的控制。DGAVP在大多数接受治疗的猴子中减少了饮酒行为的习得。饮酒的开始会引起神经内分泌稳态的改变,例如血浆β-内啡肽增加。阿片类拮抗剂纳曲酮和阿片类激动剂吗啡在持续供应酒精期间和强制戒酒之后均剂量依赖性地减少了酒精摄入量。强制戒酒之后,猴子对这两种药物更为敏感。这些效应是在成瘾行为的内啡肽补偿假说的背景下进行解释的。有人提出,内啡肽可能与对成瘾药物的渴望以及成瘾行为的复发特别相关。

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