Kashiwa A, Nishikawa T, Nishijima K, Umino A, Takahashi K
Department of Mental Disorder Research, National Center of Neurology and Psychiatry, Tokyo, Japan.
Neurochem Int. 1995 Mar;26(3):269-79. doi: 10.1016/0197-0186(94)00125-e.
We have examined in the rat the effects of a selective non-competitive antagonist for the N-methyl-D-aspartate (NMDA) type excitatory amino acid receptor, dizocilpine (MK-801), on cortical dopamine (DA) metabolism using an in vivo dialysis technique. An acute intraperitoneal injection of MK-801 (0.4-1.25 mg/kg) dramatically increased the concentrations of dopamine, 3,4-dihydroxy-phenylacetic acid and homovanillic acid in the dialysates from the medial frontal cortex in a dose-dependent fashion. Moreover, MK-801 caused a delayed and small augmentation of the cortical extracellular release of 5-hydroxyindoleacetic acid. Continuous infusion of tetrodotoxin into the prefrontal region via the microdialysis tube completely blocked the ability of MK-801 (1.25 mg/kg, intraperitoneally) to augment the extracellular release of DA, its metabolites and the serotonin metabolite in the frontal cortex. The present results suggest that MK-801 facilitates DA release in the medial frontal cortex by increasing impulse flow in the DA neurons projecting to the cortical area adding further support to the view that the NMDA receptor may be involved in the tonic inhibition of frontal cortical DA neurons. It is also proposed that frontal serotonin neurons might be under regulation by excitatory amino acidergic transmission via the NMDA receptor.
我们运用体内透析技术，在大鼠身上研究了N-甲基-D-天冬氨酸（NMDA）型兴奋性氨基酸受体的选择性非竞争性拮抗剂地佐环平（MK-801）对皮质多巴胺（DA）代谢的影响。急性腹腔注射MK-801（0.4 - 1.25毫克/千克）能以剂量依赖的方式显著提高内侧额叶皮质透析液中多巴胺、3,4-二羟基苯乙酸和高香草酸的浓度。此外，MK-801导致5-羟吲哚乙酸的皮质细胞外释放出现延迟且幅度较小的增加。通过微透析管将河豚毒素持续注入前额叶区域，完全阻断了MK-801（1.25毫克/千克，腹腔注射）增加额叶皮质中DA、其代谢产物以及血清素代谢产物细胞外释放的能力。目前的结果表明，MK-801通过增加投射到皮质区域的DA神经元的冲动流来促进内侧额叶皮质中的DA释放，这进一步支持了NMDA受体可能参与对额叶皮质DA神经元的紧张性抑制这一观点。还提出额叶血清素神经元可能受经由NMDA受体的兴奋性氨基酸能传递的调节。
