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.
Section of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Takahisa
T
Fujihira
Sotaro
S
Kanematsu
Asami
A
Umino
Naoki
N
Yamamoto
Toru
T
Nishikawa
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