Exaggerated responses to chronic nociceptive stimuli and enhancement of N-methyl-D-aspartate receptor-mediated synaptic transmission in mutant mice lacking D-amino-acid oxidase

Formalin-induced nociceptive behaviors and N-methyl-D-aspartate (NMDA) subt ype glutamate receptor-mediated excitatory synaptic transmission were analy zed in mutant mice lacking D-amino-acid oxidase, which catalyzes the oxidat ive deamination of D-amino acids. The second phase of the formalin-induced licking response, a part of which is known to be mediated by NMDA receptors in the spinal cord, was significantly augmented in mutant mice. NMDA recep tor-mediated excitatory postsynaptic currents recorded from spinal cord dor sal horn neurons by tight-seal whole-cell methods were significantly potent iated in mutant mice. The present observations provide another line of evid ence that D-serine functions as an endogenous coagonist at the glycine site of NMDA receptors, and raise the possibility that D-amino-acid oxidase exe rts a neuromodulatory function by controlling the concentration of D-serine in the central nervous system. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.