In Vivo Modulation of the N‐Methyl‐D‐Aspartate Receptor Complex by D‐Serine: Potentiation of Ongoing Neuronal Activity as Evidenced by Increased Cerebellar Cyclic GMP

Direct intracerebellar injections of TV‐methyl‐D‐aspartate (NMDA) or D‐serine elicited dose‐dependent increases in cerebellar cyclic GMP levels, in vivo in the mouse. The actions of D‐serine were antagonized by the competitive NMDA receptor antagonist 3‐(2‐carboxypiperazin‐4‐yl) propyl‐1‐phosphonic acid and by the phen‐cyclidine receptor agonist MK‐801, observations supporting actions at the NMDA‐coupled glycine receptor. In addition, the actions of D‐serine were antagonized by a partial agonist (D‐cycloserine) and an antagonist (HA‐966) of the NMDA‐coupled glycine receptor. These data are all consistent with D‐serine acting at the NMDA‐coupled glycine receptor and represent the first demonstration of glycine receptor potentiation of ongoing NMDA‐mediated neuronal activity in the CNS, rather than potentiation of exogenous NMDA.