Markou A, Weiss F, Gold L H, Caine S B, Schulteis G, Koob G F
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
Psychopharmacology (Berl). 1993;112(2-3):163-82. doi: 10.1007/BF02244907.
Drug craving, the desire to experience the effect(s) of a previously experienced psychoactive substance, has been hypothesized to contribute significantly to continued drug use and relapse after a period of abstinence in humans. In more theoretical terms, drug craving can be conceptualized within the framework of incentive motivational theories of behavior and be defined as the incentive motivation to self-administer a psychoactive substance. The incentive-motivational value of drugs is hypothesized to be determined by a continuous interaction between the hedonic rewarding properties of drugs (incentive) and the motivational state of the organism (organismic state). In drug-dependent individuals, the incentive-motivational value of drugs (i.e., drug craving) is greater compared to non-drug-dependent individuals due to the motivational state (i.e., withdrawal) developed with repeated drug administration. In this conceptual framework, animal models of drug craving would reflect two aspects of the incentive motivation to self-administer a psychoactive substance. One aspect would be the unconditioned incentive (reinforcing) value of the drug itself. The other aspect would be relatively independent of the direct (unconditioned) incentive value of the drug itself and could be reflected in the ability of previously neutral stimuli to acquire conditioned incentive properties that could elicit drug-seeking and drug-taking behavior. Animal models of drug craving that permit the investigation of the behavioral and neurobiological components of these two aspects of drug craving are reviewed and evaluated. The models reviewed are the progressive ratio, choice, extinction, conditioned reinforcement and second-order schedule paradigms. These animal models are evaluated according to two criteria that are established herein as necessary and sufficient criteria for the evaluation of animal models of human psychopathology: reliability and predictive validity. The development of animal models of drug craving will have heuristic value and allow a systematic investigation of the neurobiological mechanisms of craving.
药物渴望,即体验先前使用过的精神活性物质效果的欲望,被认为在人类戒断一段时间后持续使用药物和复发中起重要作用。从更理论的角度来看,药物渴望可以在行为的激励动机理论框架内进行概念化,并被定义为自我给药精神活性物质的激励动机。药物的激励动机价值被认为是由药物的享乐性奖励特性(激励)与机体的动机状态(机体状态)之间的持续相互作用所决定的。在药物依赖个体中,由于反复给药所产生的动机状态(即戒断),与非药物依赖个体相比,药物的激励动机价值(即药物渴望)更大。在这个概念框架中,药物渴望的动物模型将反映自我给药精神活性物质的激励动机的两个方面。一个方面是药物本身的无条件激励(强化)价值。另一个方面相对独立于药物本身的直接(无条件)激励价值,并且可以体现在先前中性刺激获得能够引发觅药和用药行为的条件性激励特性的能力上。本文对允许研究药物渴望这两个方面的行为和神经生物学成分的药物渴望动物模型进行了综述和评估。所综述的模型有渐进比率、选择、消退、条件强化和二阶程序范式。这些动物模型根据本文确定的作为评估人类精神病理学动物模型的必要和充分标准的两个标准进行评估:可靠性和预测效度。药物渴望动物模型的发展将具有启发价值,并允许对渴望的神经生物学机制进行系统研究。