Bubser M, Tzschentke T, Hauber W
Department of Neuropharmacology, University of Tübingen, Germany.
J Neural Transm Gen Sect. 1995;101(1-3):115-26. doi: 10.1007/BF01271550.
The behavioural and neurochemical effects of the N-methyl-D-aspartate (NMDA) antagonist dizocilpine and the alpha-amino-3-hydroxy-5-methylisoxazole- 4-propionic acid (AMPA) antagonist GYKI 52466, given alone or in combination, were investigated in rats. Locomotor activity was increased by dizocilpine (0.2 mg/kg), but not by GYKI 52466 (2.4 mg/kg). Dizocilpine-induced hyperlocomotion was reduced by co-administration of GYKI 52466. In dizocilpine-treated rats dopamine (DA) metabolism (measured as DOPAC [dihydroxyphenylacetic acid] or DOPAC/DA in post mortem brain tissue) was increased in the prefrontal cortex and nucleus accumbens. In GYKI 52466-treated rats serotonin was reduced in the prefrontal cortex and nucleus accumbens while DA metabolism was not affected. In rats treated with dizocilpine plus GYKI 52466, DA metabolism was increased only in the prefrontal cortex, but not in the nucleus accumbens, when compared with vehicle-treated animals. These data confirm that AMPA and NMDA antagonists do not have synergistic effects on locomotor activity. A differential role of NMDA and AMPA antagonists in the control of mesolimbic DA neurons will be discussed here.
在大鼠中研究了单独或联合给予N-甲基-D-天冬氨酸（NMDA）拮抗剂地佐环平以及α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）拮抗剂GYKI 52466的行为和神经化学效应。地佐环平（0.2mg/kg）可增加运动活性，但GYKI 52466（2.4mg/kg）则无此作用。联合给予GYKI 52466可减轻地佐环平诱导的运动亢进。在地佐环平处理的大鼠中，前额叶皮质和伏隔核中的多巴胺（DA）代谢（以死后脑组织中的二羟基苯乙酸[DOPAC]或DOPAC/DA衡量）增加。在GYKI 52466处理的大鼠中，前额叶皮质和伏隔核中的5-羟色胺减少，而DA代谢未受影响。与溶剂处理的动物相比，在地佐环平加GYKI 52466处理的大鼠中，仅前额叶皮质中的DA代谢增加，而伏隔核中未增加。这些数据证实AMPA和NMDA拮抗剂对运动活性没有协同作用。本文将讨论NMDA和AMPA拮抗剂在中脑边缘DA神经元控制中的不同作用。
