VA Boston Healthcare System, Mental Health and Research Services, Boston, MA 02130, USA.
Pharmacol Biochem Behav. 2011 Jan;97(3):619-25. doi: 10.1016/j.pbb.2010.08.004. Epub 2010 Aug 17.
Clinical interventions which produce cue and contextual extinction learning can reduce craving and relapse in substance abuse and inhibit conditioned fear responses in anxiety disorders. In both types of disorders, classical conditioning links unconditioned drug or fear responses to associated contextual cues and result in enduring pathological responses to multiple stimuli. Extinction therapy countermeasures seek to reduce conditioned responses using a set of techniques in which patients are repeatedly exposed to conditioned appetitive or aversive stimuli using imaginal imagery, in vivo exposure, or written scripts. Such interventions allow patients to rehearse more adaptive responses to conditioned stimuli. The ultimate goal of these interventions, extinction of the original conditioned response, is a new learning process that results in a decrease in frequency or intensity of conditioned responses to drug or fear cues. This review explores extinction approaches in conditioned drug reward and fear responses. The behavioral, neuroanatomical and neurochemical mechanisms of conditioned reward and fear responses and their extinction are derived from our understanding of the animal literature. Extensive neuroscience research shows that even though many mechanisms differ in conditioned fear and reward, converging prefrontal cortical glutamatergic pathways underlie extinction learning. Efficacy of pharmacological and behavioral treatment approaches in addiction and anxiety disorders may be optimized by enhancing extinction and weakening the bond between the original conditioned stimuli and conditioned responses. Adjunctive pharmacotherapy approaches using agents which alter glutamate or γ-aminobutyric acid signaling or epigenetic mechanisms in prefrontal cortical pathways can enhance extinction learning. A comparative study of extinction processes and its neural mechanisms can be translated into more effective behavioral and pharmacological treatment approaches in substance abuse and anxiety.
临床干预措施，如产生线索和情境性消退学习，可以减少物质滥用中的渴望和复发，并抑制焦虑障碍中的条件性恐惧反应。在这两种类型的障碍中，经典条件作用将非条件药物或恐惧反应与相关的情境线索联系起来，并导致对多种刺激产生持久的病理性反应。消退疗法对策旨在使用一系列技术来减少条件反应，其中患者通过想象图像、活体暴露或书面脚本反复暴露于条件性奖赏或厌恶刺激。这些干预措施允许患者对条件刺激进行更多适应性反应的练习。这些干预措施的最终目标是消除原始条件反应，这是一个新的学习过程，导致对药物或恐惧线索的条件反应的频率或强度降低。本文探讨了条件性药物奖赏和恐惧反应的消退方法。条件性奖赏和恐惧反应及其消退的行为、神经解剖学和神经化学机制源自我们对动物文献的理解。广泛的神经科学研究表明，尽管条件性恐惧和奖赏的许多机制不同，但汇聚的前额皮质谷氨酸能途径是消退学习的基础。通过增强消退和削弱原始条件刺激与条件反应之间的联系，可以优化药物和行为治疗方法在成瘾和焦虑障碍中的疗效。使用改变前额皮质途径中谷氨酸或γ-氨基丁酸信号或表观遗传机制的药物辅助治疗方法可以增强消退学习。对消退过程及其神经机制的比较研究可以转化为物质滥用和焦虑症更有效的行为和药物治疗方法。
