Stefan & Shirley Hatos Center for Neuropharmacology, University of California Los Angeles, Los Angeles, California, USA.
Int Rev Neurobiol. 2009;89:131-46. doi: 10.1016/S0074-7742(09)89006-5.
The past decade has witnessed an impressive accumulation of evidence indicating that the excitatory amino acid glutamate and its receptors, in particular the N-methyl-D-aspartate (NMDA) receptor subtype, play an important role in drug addiction. Various lines of research using animal models of drug addiction have demonstrated that drug-induced craving is accompanied by significant upregulation of NR2B subunit expression. Furthermore, selective blockade of NR2B-containing NMDA receptors in the striatum, especially in the nucleus accumbens (NAc) can inhibit drug craving and reinstatement. The purpose of this review is to examine the role of striatal NMDA receptors in drug addiction. After a brief description of glutamatergic innervation and NMDA receptor subunit distribution in the striatum, we discuss potential mechanisms to explain the role of striatal NMDA receptors in drug addiction by elucidating signaling cascades involved in the regulation of subunit expression and redistribution, phosphorylation of receptor subunits, as well as activation of intracellular signals triggered by drug experience. Understanding the mechanisms regulating striatal NMDA receptor changes in drug addiction will provide more specific and rational targets to counteract the deleterious effects of drug addiction.
过去十年的研究积累了令人瞩目的证据，表明兴奋性氨基酸谷氨酸及其受体，特别是 N-甲基-D-天冬氨酸（NMDA）受体亚基，在药物成瘾中发挥着重要作用。利用药物成瘾动物模型的各种研究表明，药物引起的渴望伴随着 NR2B 亚基表达的显著上调。此外，选择性阻断纹状体中包含 NR2B 的 NMDA 受体，特别是在伏隔核（NAc）中，可以抑制药物渴望和复吸。本综述的目的是探讨纹状体 NMDA 受体在药物成瘾中的作用。在简要描述纹状体中的谷氨酸能神经支配和 NMDA 受体亚基分布后，我们通过阐明参与调节亚基表达和重分布、受体亚基磷酸化以及药物经验触发的细胞内信号转导的信号级联，讨论了纹状体 NMDA 受体在药物成瘾中作用的潜在机制。了解调节纹状体 NMDA 受体变化的机制将为对抗药物成瘾的有害影响提供更具体和合理的靶点。
