Svensson A, Pileblad E, Carlsson M
Department of Pharmacology, University of Göteborg, Sweden.
J Neural Transm Gen Sect. 1991;85(2):117-29. doi: 10.1007/BF01244704.
Following intraperitoneal administration of the non-competitive N-methyl-D-aspartate (NMDA) antagonist dizocilpine (MK-801), levels of the dopamine (DA) metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) increased in mouse striatum and limbic forebrain. When dizocilpine was given to animals treated with NSD 1015, an inhibitor of 3,4-dihydroxyphenylalanine (DOPA) decarboxylase and monoamine oxidase, there was an increase in levels of DOPA and 3-methoxytyramine (3-MT). These findings suggest that dizocilpine stimulates DA synthesis and release in mouse brain. Following dizocilpine treatment a clear-cut increase in spontaneous locomotor activity was observed, probably partly due to enhanced dopaminergic tone. The competitive NMDA antagonist D-CPPene produced locomotor stimulation as well, but in contrast to following dizocilpine treatment levels of 3-MT decreased. Thus the stimulation of locomotor activity following D-CPPene treatment does not seem to be mediated through activation of central dopaminergic systems. However, haloperidol pretreatment antagonized this locomotor response, indicating that the dopaminergic system plays a permissive role in this context.
腹腔注射非竞争性 N-甲基-D-天冬氨酸（NMDA）拮抗剂地佐环平（MK-801）后，小鼠纹状体和边缘前脑的多巴胺（DA）代谢产物 3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）水平升高。当给用 NSD 1015（一种 3,4-二羟基苯丙氨酸（DOPA）脱羧酶和单胺氧化酶抑制剂）处理的动物注射地佐环平时，DOPA 和 3-甲氧基酪胺（3-MT）水平升高。这些发现表明地佐环平刺激小鼠脑内 DA 的合成和释放。地佐环平处理后，观察到自发运动活动明显增加，这可能部分归因于多巴胺能张力增强。竞争性 NMDA 拮抗剂 D-CPPene 也产生运动刺激，但与地佐环平处理后不同的是，3-MT 水平下降。因此，D-CPPene 处理后运动活动的刺激似乎不是通过激活中枢多巴胺能系统介导的。然而，氟哌啶醇预处理可拮抗这种运动反应，表明多巴胺能系统在这种情况下起允许作用。
