中枢N-甲基-D-天冬氨酸受体在应激所致行为改变中的作用

应激所致行为效应的脑机制研究是目前生理心理学研究的热点领域。近年来，对于参与应激所致行为效应的神经递质研究从5-HT、多巴胺和去甲肾上腺素的范畴，逐渐发展到关注脑内含量最为丰富的谷氨酸能神经元所产生的兴奋性递质，包括谷氨酸、天冬氨酸及其相应受体NMDAR可能在应激性行为效应的中枢机制中的作用。近十年来的研究表明，中枢NMDAR是学习记忆的关键物质，在兴奋性突触传递、突触可塑性和脑发育过程中扮演重要的角色。不同类型的应激能导致动物的与行为密切相关脑区如杏仁核，海马的兴奋性氨基酸及NMDAR数量增多，活性增高。突触间隙增多的兴奋性氨基酸与NMDAR结合后，通过激活NMDAR促进糖皮质激素的相关性释放，共同产生的兴奋毒性作用引起上述脑区的神经元细胞缺失和变性；或干扰其他中枢神经递质在动物行为的脑内奖赏机制中的正常功能；或通过持续激活NMDAR，导致细胞内Ca2＋超载，损害其信号传导途径下游的蛋白激酶级联反应，使其底物蛋白的磷酸化或去磷酸化作用发生改变，影响突触可塑性和神经细胞间的信号传递，导致动物出现相应的行为障碍。应激前给动物的上述脑区注射NMDAR阻滞剂，可以减轻动物的应激性焦虑和抑郁行为。而NMDAR依赖性LTP下游途径的新信号分子，神经颗粒素，参与了脑内多种蛋白信号传导，可能是应激性行为效应的另一重要中枢机制。

Involvement of N-methyl-D-aspartate Receptors in Stress-Induced Behavioral Changes

Studies in the physiological psychology field have been focused on the brain mechanisms underlying stress-induced behavioral changes. The role of NMDA receptor (NR) in mediating stress-induced behavioral changes has gained more and more attention. NR is important for synaptic plasticity, brain development, and learning and memory. It has been shown that different stressors up-regulate the level or activity of NR in some brain regions, such as hippocampus and amygdale. Injection of the NR antagonist into these regions prior to stress can reduce stress-induced anxiety and depression, suggesting that NR are important mediators of stress-induced behavioral changes. N-methyl-D-aspartate receptors are important substance related closely with stress response and participate the process of brain damage caused by stress. N-methyl-D-aspartate receptor antagonists may be useful for treatment of stress-related mental disorder, such as recurrent depression, posttraumatic stress disorder. Furthermore, studies on neurogranin, a downstream signal molecule in NR-dependant transduction pathway, provided further information about the mechanisms underlying the effects of stress on behavior.