N-methyl-D-aspartate receptors modulate extracellular 5-hydroxytryptamine concentration in rat hippocampus and striatum in vivo.

The effects of infusing N-methyl-D-aspartate (NMDA) and the specific NMDA receptor antagonist D-2-amino-5-phosphonopropionic acid (D-AP5) into rat hippocampus and striatum on extracellular 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxy-indoleacetic acid (5-HIAA) were studied using intracerebral microdialysis. In striatum, NMDA (1-100 microM) caused a concentration-dependent increase in 5-HT. D-AP5 (10 microM) infusion caused increased extracellular 5-HT. When the two drugs were co-infused, no effect on extracellular 5-HT was seen. D-AP5 alone was found to cause a delayed but sustained increase in dialysate 5-HIAA. In hippocampus, NMDA infusion caused a dose-dependent decrease in extracellular 5-HT while D-AP5 produced a transitory increase in 5-HT level. NMDA caused a decrease in dialysate 5-HIAA. In striatum, the effect of 10 microM NMDA infusion was abolished by co-infusion with tetrodotoxin (TTX; 1 microM). In hippocampus, 1 microM TTX caused a slight but non-significant augmentation of the effect of 10 microM NMDA alone. These data indicate that NMDA receptors mediate control over 5-HT release and metabolism in different brain regions and may in part explain the behavioural effects of non-competitive NMDA receptor antagonists.