Wang T, French E D
Department of Pharmacology, University of Arizona, College of Medicine, Tucson 85724.
Synapse. 1993 Mar;13(3):270-7. doi: 10.1002/syn.890130310.
In vitro extracellular single-unit recordings from rat midbrain slices were used to assess the effects of excitatory amino acid agonists on the activity of A10 dopamine neurons. N-methyl-D-aspartic acid (NMDA), kainic acid (KA), and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) elicited dose-dependent increases in firing rates. The relative potencies for the 3 compounds was AMPA > KA > NMDA. None of the excitations was accompanied by burst firing, but frequently periods of nonrecordable activity occurred following pronounced stimulation. Concurrent application of the excitatory amino acid antagonist CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylate) selectively blocked the excitations elicited by NMDA but not by KA or AMPA. Likewise the selective non-NMDA antagonist NBQX [2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline] blocked only the excitatory effects of AMPA and KA but not those elicited by NMDA. NBQX appeared to be less potent at antagonizing KA than AMPA. These results suggest that mesolimbic-mesocortical dopamine neurons possess both NMDA and non-NMDA receptors, and possibly distinct AMPA and KA recognition sites.
利用大鼠中脑切片的体外细胞外单单位记录来评估兴奋性氨基酸激动剂对A10多巴胺神经元活性的影响。N-甲基-D-天冬氨酸（NMDA）、 kainic酸（KA）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）引起放电频率呈剂量依赖性增加。这3种化合物的相对效力为AMPA＞KA＞NMDA。所有兴奋均未伴有爆发式放电，但在强烈刺激后经常出现无法记录活动的时期。同时应用兴奋性氨基酸拮抗剂CGS 19755（顺式-4-膦酰甲基-2-哌啶羧酸）可选择性阻断NMDA引起的兴奋，但不能阻断KA或AMPA引起的兴奋。同样，选择性非NMDA拮抗剂NBQX [2,3-二羟基-6-硝基-7-氨磺酰基-苯并（F）喹喔啉]仅阻断AMPA和KA的兴奋作用，而不阻断NMDA引起的兴奋作用。NBQX拮抗KA的效力似乎低于拮抗AMPA。这些结果表明，中脑边缘-中脑皮质多巴胺神经元同时具有NMDA和非NMDA受体，可能还有不同的AMPA和KA识别位点。
