Hong Jin-Tae, Kim Hyoung-Chun, Kim Hack-Seang, Lee Yong-Moon, Oh Ki-Wan
Department of Pharmacy, College of Pharmacy, Chungbuk National University, Cheongju 371-763, South Korea.
Pharmacol Res. 2005 Oct;52(4):298-301. doi: 10.1016/j.phrs.2005.05.002.
Biochemical studies have been demonstrated that N-methyl-D-aspartate (NMDA)-evoked dopaminergic (DAergic) activation can be modulated by nitric oxide (NO) systems. Therefore, behavioral study was performed to characterize the role of NO on NMDA modulation of DAergic activation. It is well known that apomorphine induces climbing behaviors in mice by the activation of DAergic receptors. Our previous studies showed that NMDA receptor antagonists reduced apomorphine-induced climbing behaviors. It was reported that nitric oxide synthase (NOS) inhibitors reduced the apomorphine-induced climbing behaviors. In this experiment, NO donor restored the apomorphine-induced climbing behavior, which was inhibited by NMDA receptor antagonist. NOS inhibitor inhibited the apomorphine-induced climbing behavior, which was enhanced by NMDA receptor agonist. These results suggest that DAergic activation is regulated by both NMDA receptors and NO systems, and NO in the down-stream of NMDA receptors play an important role on the glutaminergic NMDA modulation of DAergic function.
生化研究已证明，N-甲基-D-天冬氨酸（NMDA）诱发的多巴胺能（DAergic）激活可被一氧化氮（NO）系统调节。因此，进行了行为学研究以表征NO在NMDA对DAergic激活的调节中的作用。众所周知，阿扑吗啡通过激活DAergic受体诱导小鼠的攀爬行为。我们之前的研究表明，NMDA受体拮抗剂可减少阿扑吗啡诱导的攀爬行为。据报道，一氧化氮合酶（NOS）抑制剂可减少阿扑吗啡诱导的攀爬行为。在本实验中，NO供体恢复了被NMDA受体拮抗剂抑制的阿扑吗啡诱导的攀爬行为。NOS抑制剂抑制了被NMDA受体激动剂增强的阿扑吗啡诱导的攀爬行为。这些结果表明，DAergic激活受NMDA受体和NO系统两者调节，且NMDA受体下游的NO在谷氨酸能NMDA对DAergic功能的调节中起重要作用。
