Effects of N-methyl-D-aspartate, kainate or veratridine on extracellular concentrations of free D-serine and L-glutamate in rat striatum: an in vivo microdialysis study.
Using an in vivo microdialysis technique, we have investigated the effect of N-methyl-D-aspartate (NMDA) or kainate on the extracellular concentrations of free D-serine and L-glutamate in the striatum. A intrastriatal perfusion of NMDA or kainate caused a significant increase in the extracellular release of L-glutamate, but a significant decrease in that of D-serine. Co-perfusion of an NMDA receptor antagonist, MK-801, or an alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid/kainate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), with NMDA or kainate significantly reversed the NMDA- or kainate-induced decrease in the extracellular level of D-serine, respectively. The NMDA- or kainate-evoked increase in the extracellular L-glutamate level was also reversed by co-perfusion of MK-801 or CNQX, respectively. Because D-serine acts as a potent and selective agonist for the glycine site of the NMDA receptor and because intracerebroventricularly injected D-serine is accumulated in the astrocytes, D-serine could be taken up by the astrocytes following synaptic activation. Furthermore, because cortical ablation to remove corticostriatal glutamatergic inputs attenuates the excitotoxic effects of kainate in the striatum, L-glutamate may enhance its own release through a presynaptic NMDA and/or non-NMDA receptor-mediated mechanism.
Hashimoto
A
A
Department of Pharmacology, School of Medicine, Tokai University, Isehara, Kanagawa, Japan. hashimot@is.icc.u-tokai.ac.jp
Kanda
J
J
Oka
T
T
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005110:Extracellular Space; D018698:Glutamic Acid / Q000187:drug effects* / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014701:Veratridine / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D012694:Serine; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D014701:Veratridine; D007608:Kainic Acid