The role of nitric oxide on glutaminergic modulation of dopaminergic activation

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.