Enhancement of NMDA-evoked neuronal activity by glycine in the rat spinal cord in vivo

The effects of iontophoretically administered N-methyl-d-aspartate (NMDA), glycine and strychnine on nociceptive dorsal horn neurons of the rat spinal cord were studied to test the hypothesis that their responses to NMDA are influenced in vivo by glycine acting at a strychnine-insensitive site. Experiments were carried out on 44 dorsal horn neurons responsive to microiontophoretic application of NMDA and peripheral stimulation. Glycine alone either enhanced or inhibited NMDA responses depending upon its dose (151% and 68% of control, respectively). Strychnine alone increased the NMDA-induced neural firing (129%), suggesting the presence of endogenous glycine. When glycine was co-ejected with strychnine, NMDA responses were further elevated (171%) revealing the activation of strychnine-insensitive binding sites. These data provide evidence that glycine can potentiate NMDA responses of nociceptive dorsal horn neurons in vivo and thus that glycine sites on NMDA receptors on these neurons are not saturated.