Sakai K, Akiyama K, Kashihara K, Tsuchida K, Ujike H, Kuroda S, Shohmori T
Department of Neurology, Okayama University Medical School, Japan.
Neurochem Int. 1997 Mar;30(3):329-36. doi: 10.1016/s0197-0186(96)00047-2.
The effect of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f) quinoxaline (NBQX), a potent and selective antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, on the release of dopamine from the striatum was investigated in freely moving rats using an in vivo microdialysis technique. Perfusion with 1.0 mM AMPA increased the concentration of striatal extracellular dopamine. After systemic administration of NBQX (40 mg/kg, i.p.), dopamine levels in the striatal perfusate decreased. The AMPA-induced increase in dopamine levels was suppressed significantly by the systemic administration of NBQX (40 mg/kg, i.p.). Perfusion with tetrodotoxin (TTX, 5 microM) alone reduced the basal level of dopamine by 80%. Perfusion with 1.0 mM AMPA together with TTX produced a 3.9-fold increase in dopamine efflux from the TTX reduced basal level. However, the maximum dopamine level obtained thereby was close to the basal level of dopamine seen prior to perfusion with TTX. The present results demonstrate that AMPA receptors participate in tonic facilitative modulation of striatal extracellular level of dopamine. In addition, the results support the view that glutamatergic neurons modulate the release of dopamine via subtypes of excitatory amino acid receptors in the central nervous system.
使用体内微透析技术，在自由活动的大鼠中研究了强效且选择性的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂2,3-二羟基-6-硝基-7-氨磺酰基苯并[f]喹喔啉（NBQX）对纹状体中多巴胺释放的影响。用1.0 mM AMPA灌注可增加纹状体细胞外多巴胺的浓度。全身给予NBQX（40 mg/kg，腹腔注射）后，纹状体灌流液中的多巴胺水平降低。全身给予NBQX（40 mg/kg，腹腔注射）可显著抑制AMPA诱导的多巴胺水平升高。单独用河豚毒素（TTX，5 microM）灌注可使多巴胺的基础水平降低80%。将1.0 mM AMPA与TTX一起灌注可使多巴胺从TTX降低的基础水平外流增加3.9倍。然而，由此获得的最大多巴胺水平接近灌注TTX之前所见的多巴胺基础水平。目前的结果表明，AMPA受体参与对纹状体细胞外多巴胺水平的紧张性促进调节。此外，这些结果支持谷氨酸能神经元通过中枢神经系统中兴奋性氨基酸受体亚型调节多巴胺释放的观点。
