Koob G F, Stinus L, Le Moal M, Bloom F E
Department of Neuropharmacology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Neurosci Biobehav Rev. 1989 Summer-Fall;13(2-3):135-40. doi: 10.1016/s0149-7634(89)80022-3.
One hypothetical model for a mechanism of drug dependence involves the development of an adaptive process that is initiated to counter the acute effects of the drug. This adaptive process persists after the drug has been cleared from the brain, leaving an opposing reaction unopposed (abstinence signs). From a motivational perspective a particularly attractive hypothesis has been that of opponent process theory (32). Here many reinforcers elicit positive affective and hedonic processes that are opposed by negative affective and hedonic processes. Thus the intense pleasure of the opiate drug "rush" or "high" would be opposed by aversive withdrawal symptoms. The present paper presents neurobiological evidence to support the opponent process concept and suggests neural circuitry that may be involved. The region of the nucleus accumbens in the forebrain of the rat has been shown to be a particularly sensitive substrate not only for the acute reinforcing properties of opiate drugs, but also for the response disruptive effects of opiate antagonists in opiate dependent rats. This region also appears to be particularly sensitive to the aversive stimulus effects of opiate antagonists using a place aversion measure in dependent rats. These results suggest that the region of the nucleus accumbens and its neural circuitry may be an important neural substrate for both the positive and negative motivational aspects of drug dependence.
一种关于药物依赖机制的假设模型涉及一种适应性过程的发展，该过程是为了对抗药物的急性效应而启动的。在药物从大脑中清除后，这种适应性过程仍然存在，导致一种相反的反应没有受到对抗（戒断症状）。从动机的角度来看，一个特别有吸引力的假说是对立过程理论（32）。在这里，许多强化物会引发积极的情感和享乐过程，这些过程会被消极的情感和享乐过程所对抗。因此，阿片类药物“快感”或“兴奋感”带来的强烈愉悦会被厌恶的戒断症状所对抗。本文提供了神经生物学证据来支持对立过程的概念，并提出了可能涉及的神经回路。大鼠前脑伏隔核区域已被证明是一个特别敏感的底物，不仅对阿片类药物的急性强化特性敏感，而且对阿片类拮抗剂对阿片类依赖大鼠的反应干扰作用也敏感。使用场所厌恶测量方法，该区域似乎对阿片类拮抗剂对依赖大鼠的厌恶刺激效应也特别敏感。这些结果表明，伏隔核区域及其神经回路可能是药物依赖的正向和负向动机方面的重要神经底物。
