THE PARTIAL NMDA AGONIST D-CYCLOSERINE STIMULATES LH-SECRETION IN HEALTHY-VOLUNTEERS

D-Cycloserine, a partial agonist of the glycine recognition site of th e N-methyl-D-aspartate (NMDA) receptor, may serve as a probe for human cerebral NMDA receptor function. Since NMDA receptors are involved in neuroendocrine secretion, changes in pituitary secretion in response to D-cycloserine administration could serve as a model for NMDA recept or activity. The effects of an oral dose of 500mg D-cycloserine were a ssessed in a neuroendocrine challenge paradigm in 20 healthy male volu nteers, using a double-blind. randomized placebo-controlled crossover design. Luteinizing hormone (LH) and cortisol secretion was studied, s ince preclinical studies indicate that these hormones increase in resp onse to NMDA receptor stimulation. Furthermore, plasma homovanillic ac id (HVA) secretion was studied, as NMDA receptors are suggested to be involved in the regulation of dopaminergic neurotransmission. D-cyclos erine was readily absorbed and did not induce side-effects or changes in vital signs and mood scores. D-Cycloserine stimulated LH secretion and induced a significant rise of the area under the plasma concentrat ion time curve of LH. D-Cycloserine did not stimulate cortisol or plas ma HVA secretion. These neuroendocrine effects suggest that D-cycloser ine may be used to assess human NMDA receptor function in cerebral dis orders, such as schizophrenia.