Schulteis G, Koob G F
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA, USA.
Neurochem Res. 1996 Nov;21(11):1437-54. doi: 10.1007/BF02532385.
The development of tolerance and dependence has traditionally been considered an integral aspect of the drug addiction process, and opiate dependence has been studied extensively as a model system in this regard. However, recent emphasis on the positive reinforcing properties of drugs has led to the suggestion that tolerance, dependence, and withdrawal may be of secondary or even negligible importance in motivating compulsive drug use. The current article argues for an integrated view of addiction in the form of a homeostatic neuroadaptation model which emphasizes the motivational significance of both the positive affective state produced by opiates and the negative affective state characteristic of drug withdrawal. The model is supported by evidence at both the behavioral and neural systems levels of analysis. Understanding the important distinction between somatic and affective components of opiate withdrawal is key to recognizing the factors which contribute to the motivational significance of opiate dependence and withdrawal. In addition, the critical role of conditioning processes in the maintenance of compulsive drug use and relapse after periods of abstention is discussed. Finally, it is argued that both the positive reinforcement produced by acute administration of a drug and the negative affective state produced by withdrawal are common to multiple classes of abused drugs, suggesting that an understanding of homeostatic neuroadaptation within motivational systems provides a key to the etiology, treatment and prevention of drug addiction.
耐受性和依赖性的发展传统上被视为药物成瘾过程的一个重要方面，在这方面，阿片类药物依赖性作为一个模型系统已得到广泛研究。然而，最近对药物积极强化特性的强调引发了一种观点，即耐受性、依赖性和戒断反应在驱使强迫性药物使用方面可能处于次要地位甚至可以忽略不计。本文主张以一种稳态神经适应模型的形式对成瘾进行综合考量，该模型强调阿片类药物产生的积极情感状态以及药物戒断的消极情感状态的动机意义。这一模型在行为和神经系统分析层面均有证据支持。理解阿片类药物戒断的躯体和情感成分之间的重要区别，是认识导致阿片类药物依赖性和戒断动机意义的因素的关键。此外，还讨论了条件作用过程在维持强迫性药物使用以及戒断一段时间后的复吸中的关键作用。最后，有人认为药物急性给药产生的积极强化作用和戒断产生的消极情感状态在多种滥用药物中都很常见，这表明理解动机系统内的稳态神经适应为药物成瘾的病因、治疗和预防提供了关键。
