Koob G F, Rocio M, Carrera A, Gold L H, Heyser C J, Maldonado-Irizarry C, Markou A, Parsons L H, Roberts A J, Schulteis G, Stinus L, Walker J R, Weissenborn R, Weiss F
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
J Psychopharmacol. 1998;12(1):39-48. doi: 10.1177/026988119801200106.
A compulsion to take a drug combined with a loss of control in limiting intake is the defining feature of substance dependence or addiction, and is the conceptual framework for the criteria of substance dependence or addiction outlined by the World Health Organization and the American Psychiatric Association. However, defining exactly what constitutes loss of control and compulsive drug taking at the level of animal models is a daunting task, and it is clear that no validated animal model exists for the whole syndrome of addiction. The present discussion redefines loss of control as a narrowing of the behavioral repertoire toward drug-seeking behavior and suggests that there are many sources of reinforcement that contribute to this behavioral focus on drug seeking. Evidence is presented demonstrating separate animal models for many of these sources of reinforcement as well as for most of the criteria for substance dependence. Evidence is also presented showing that the brain neurochemical systems involved in processing drug reward are altered by chronic drug exposure to contribute additional sources of reinforcement. Challenges for the future involve not only elucidation of the neurobiological substrates of the different behavioral components of addiction, but better animal models of these components with which to effect such studies.
对药物的强迫性使用以及在限制摄入量方面失去控制，是物质依赖或成瘾的决定性特征，也是世界卫生组织和美国精神病学协会所概述的物质依赖或成瘾标准的概念框架。然而，在动物模型层面准确界定什么构成失去控制和强迫性药物使用是一项艰巨的任务，而且显然不存在针对整个成瘾综合征的经过验证的动物模型。本讨论将失去控制重新定义为行为模式向寻求药物行为的收缩，并表明有许多强化源促成了这种对寻求药物行为的行为聚焦。文中呈现的证据表明，针对许多这些强化源以及物质依赖的大多数标准，都有各自独立的动物模型。还呈现了证据表明，参与处理药物奖赏的大脑神经化学系统会因长期药物暴露而改变，从而促成额外的强化源。未来的挑战不仅涉及阐明成瘾不同行为成分的神经生物学基础，还涉及用于开展此类研究的更好的这些成分的动物模型。
