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.

Abstract Formalin-induced nociceptive behaviors and N -methyl- d -aspartate (NMDA) subtype glutamate receptor-mediated excitatory synaptic transmission were analyzed in mutant mice lacking d -amino-acid oxidase, which catalyzes the oxidative 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 receptor-mediated excitatory postsynaptic currents recorded from spinal cord dorsal horn neurons by tight-seal whole-cell methods were significantly potentiated in mutant mice. The present observations provide another line of evidence that d -serine functions as an endogenous coagonist at the glycine site of NMDA receptors, and raise the possibility that d -amino-acid oxidase exerts a neuromodulatory function by controlling the concentration of d -serine in the central nervous system.