ABSTRACT
A partial agonist of the N-methyl-D-aspartate (NMDA) receptor, D-cycloserine, acting at its glycine modulatory site, ameliorates the neuropsychiatric symptoms that are mimicked by NMDA antagonists and include cognitive disturbances, antipsychotic-resistant schizophrenic symptoms and cerebellar ataxia. To obtain a further insight into the mechanisms of the therapeutic efficacies of D-cycloserine, we investigated the effects of the systemic administration of D-cycloserine on the extracellular contents of an endogenous NMDA co-agonist, D-serine, in the medial frontal cortex of the rat using an in vivo dialysis technique. An acute intraperitoneal injection of D-cycloserine (50 and 100 mg/kg) caused an increase in extracellular concentrations of D-serine without significant effects on those of L-serine, glycine, L-glutamate, L-aspartate, L-glutamine, L-asparagine, L-alanine, L-threonine and taurine in the medial frontal cortex. The selective increase in the extracellular D-serine contents may, at least partially, be associated with the facilitating effects of D-cycloserine on the NMDA receptor functions in addition to its direct stimulation of the NMDA receptor glycine site.
