Glutamate receptors in extinction and extinction-based therapies for psychiatric illness.
Glutamate receptors in extinction and extinction-based therapies for psychiatric illness.
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DOI：
10.1038/npp.2010.88
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发表时间：
2011-01
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--
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一些精神疾病涉及到习得的成分。例如，在创伤后应激障碍中，与创伤相关的线索引发的记忆会引发恐惧和焦虑，而在成瘾中，与毒品有关的线索会引发对毒品的渴望和戒断。减少条件性提示在引发这些不适应的条件性反应中的影响的临床干预可能是有益的。消亡是一种减少条件性反应的方法，它涉及在没有它曾经预测的事件的情况下反复暴露于一个线索。我们相信，对灭绝的行为和神经生物学机制的了解的提高将使临床上的灭绝类程序变得更加有效。对谷氨酸-哺乳动物大脑中主要的兴奋性神经递质-在灭绝中的作用的研究导致了药物疗法的发展，以增强基于灭绝的方案在临床人群中的疗效。在这篇综述中，我们描述了谷氨酸在其三种主要受体类型(NMDA受体、AMPA受体和代谢性谷氨酸受体)在消除条件性恐惧、药物渴望和戒断中的作用。然后我们讨论这些发现是如何应用于临床研究的。
Some psychiatric illnesses involve a learned component. For example, in PTSD, memories triggered by trauma-associated cues trigger fear and anxiety, and in addiction, drug-associated cues elicit drug craving and withdrawal. Clinical interventions to reduce the impact of conditioned cues in eliciting these maladaptive conditioned responses are likely to be beneficial. Extinction is a method of lessening conditioned responses and involves repeated exposures to a cue in the absence of the event it once predicted. We believe that an improved understanding of the behavioral and neurobiological mechanisms of extinction will allow extinction-like procedures in the clinic to become more effective. Research on the role of glutamate – the major excitatory neurotransmitter in the mammalian brain – in extinction has led to the development of pharmacotherapeutics to enhance the efficacy of extinction-based protocols in clinical populations. In this review we describe what has been learned about glutamate actions at its three major receptor types (NMDA receptors, AMPA receptors, and metabotropic glutamate receptors) in extinction of conditioned fear, drug craving, and withdrawal. We then discuss how those findings have been applied in clinical research.
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