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.
Whitton
P S
PS
Department of Pharmacology, School of Pharmacy, London, UK.
Richards
D A
DA
Biggs
C S
CS
Fowler
L J
LJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D016194:Receptors, N-Methyl-D-Aspartate; D012701:Serotonin; D013779:Tetrodotoxin; D006897:Hydroxyindoleacetic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate