Stress activation of mesocorticolimbic dopamine neurons: effects of a glycine/NMDA receptor antagonist.
Stress activation of mesocorticolimbic dopamine neurons: effects of a glycine/NMDA receptor antagonist.
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中皮质边缘多巴胺神经元的应激激活：甘氨酸/NMDA 受体拮抗剂的作用。
DOI：
10.1016/0014-2999(93)90855-c
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发表时间：
1993
影响因子：
5
通讯作者：
Roth,RH
中科院分区：
文献类型：
--
作者：
Morrow,BA;Clark,WA;Roth,RH
短暂的抑制会引起中皮质和一些中脑边缘多巴胺能系统的代谢激活，而对黑质纹状体系统几乎没有影响。我们检测了N-甲基-D-天冬氨酸受体复合体的变构甘氨酸位置的拮抗剂在多巴胺利用中阻断应激诱导反应的能力。30分钟的束缚应激增加了内侧前额叶皮质和伏核中的多巴胺代谢，以3，4-二羟基苯乙酸(DOPAC)和多巴胺的比率来衡量。甘氨酸/N-甲基-D-天冬氨酸受体复合体的拮抗剂1-羟基-3-氨基吡咯烷酮-2((+)-HA-966)，全身给药或注射到腹侧被盖区，可阻止应激诱导的前额叶皮质多巴胺代谢增加，而不改变伏隔核的反应。类似地，全身应用N-甲基-D-天冬氨酸受体的非竞争性拮抗剂地佐西平((+)-MK-801)可阻断应激诱导的内侧前额叶皮质多巴胺代谢的升高，但不能阻断伏核。HA-966的阴性对映体不能选择性拮抗应激诱导的内侧前额叶皮质的多巴胺代谢。这些结果支持了以前的工作，即中皮质和中伏隔核的多巴胺神经元通过不同的谷氨酸受体机制对兴奋性输入做出反应。此外，甘氨酸拮抗剂对应激诱导的内侧前额叶皮质多巴胺代谢变化的特异性阻断暗示了这种拮抗剂在治疗疾病状态中的作用，这种疾病状态可能涉及N-甲基-D-天冬氨酸受体功能的破坏。
Restraint of brief duration causes a metabolic activation of mesocortical and some mesolimbic dopaminergic systems with little effect on the nigrostriatal system. We have examined the ability of an antagonist of the allosteric glycine site of the N-methyl-D-aspartate receptor complex to block the stress-induced response in dopamine utilization. Thirty minutes of restraint stress elevated dopamine metabolism, as measured by the ratio between 3,4-dihydroxyphenylacetic acid (DOPAC) and dopamine, in both the medial prefrontal cortex and nucleus accumbens. An antagonist for the glycine/N-methyl-D -aspartate receptor complex, 1-hydroxy-3-aminopyrrolidone-2 ((+)-HA-966), given systemically or injected into the ventral tegmental area, prevents the stress-induced increase in dopamine metabolism in the prefrontal cortex without altering the response in the nucleus accumbens. Similarly, systemic administration of the non-competitive antagonist for the N-methyl-D-aspartate receptor, dizocilpine ((+)-MK-801), blocked the stress-induced rise in dopamine metabolism in the medial prefrontal cortex but not the nucleus accumbens. The negative enantiomer of HA-966 did not produce a selective antagonism of the stress-induced dopamine metabolism in the medial prefrontal cortex. These results support previous work which suggest the mesocortical and mesoaccumbens dopamine neurons respond to excitatory input through different glutamate receptor mechanisms. Additionally, the specific blockade of the stress-induced change in dopamine metabolism in the medial prefrontal cortex by a glycine antagonist implies a role for such an antagonist in treatment of disease states which may involve disruptions of N-methyl-D-aspartate receptor function.