Department of Neuroscience, Centre for Addiction and Mental Health, Canada; Division of Life Sciences, Komaba Organization for Educational Excellence, College of Arts and Sciences, University of Tokyo,Tokyo 153-8902, Japan.
Brain Res. 2012 Oct 2;1476:154-63. doi: 10.1016/j.brainres.2012.03.029. Epub 2012 Mar 17.
Many pathological processes are associated with a malfunction of one or multiple post-synaptic neurotransmitter receptors. It would seem that simple agonists or antagonists at these receptors should be able to correct the pathological condition. However, these drugs often fail due to serious side effects that are caused by suppressing post-synaptic responses necessary for normal brain function. Thus, there is a need for new drugs that can selectively target specific post-synaptic pathways. The dopamine and glutamate receptor systems have been implicated in many neuropsychiatric disorders. Dopamine, the predominant catecholamine in the mammalian brain, influences a variety of functions including locomotor activity, cognition, emotion and endocrine regulation. Glutamate is the principal excitatory neurotransmitter, involved in regulating neuronal circuit development, learning and memory. The overlap and convergence of both dopaminergic and glutamatergic projections in the brain provides a framework for complex neuronal interactions between these receptor systems. In this review, we will focus on interactions between the NMDA glutamate receptor and dopamine D1 and D2 receptors, and address the potential value of receptor heteromers in seeking novel therapeutic targets. This article is part of a Special Issue entitled: Brain Integration.
许多病理过程都与一个或多个突触后神经递质受体的功能障碍有关。似乎这些受体的简单激动剂或拮抗剂应该能够纠正病理状况。然而，这些药物常常由于抑制正常大脑功能所必需的突触后反应而产生严重的副作用而失败。因此，需要能够选择性靶向特定突触后途径的新药。多巴胺和谷氨酸受体系统与许多神经精神疾病有关。多巴胺是哺乳动物大脑中的主要儿茶酚胺，影响多种功能，包括运动活动、认知、情绪和内分泌调节。谷氨酸是主要的兴奋性神经递质，参与调节神经元回路的发育、学习和记忆。大脑中多巴胺能和谷氨酸能投射的重叠和会聚为这些受体系统之间的复杂神经元相互作用提供了一个框架。在这篇综述中，我们将重点讨论 NMDA 谷氨酸受体与多巴胺 D1 和 D2 受体之间的相互作用，并探讨受体杂合体在寻找新的治疗靶点方面的潜在价值。本文是题为“大脑整合”的特刊的一部分。
