Selective increase in the extracellular d-serine contents by d-cycloserine in the rat medial frontal cortex

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-threonin 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.