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-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.
Fujihira
Takahisa
T
Section of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Kanematsu
Sotaro
S
Umino
Asami
A
Yamamoto
Naoki
N
Nishikawa
Toru
T
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003523:Cycloserine / Q000494:pharmacology* / Q000627:therapeutic use; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D045604:Extracellular Fluid / Q000378:metabolism*; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism; D007263:Infusions, Parenteral; D008297:Male; D017551:Microdialysis; D011618:Psychotic Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D018009:Receptors, Glycine / Q000819:agonists / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D013237:Stereoisomerism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D014150:Antipsychotic Agents; D018690:Excitatory Amino Acid Agonists; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D012694:Serine; D003523:Cycloserine