Effect of systemic administration of D-serine on the levels of D- and L-serine in several brain areas and periphery of rat.
To obtain further insight into the distribution and metabolism of exogenous D-serine, we have investigated the effect of the intraperitoneal administration of D-serine (10 mmol/kg) on the concentrations of D- and L-serine in several brain areas and periphery of infant and adult rats. The administration produced a significant augmentation of the D-serine levels not only in the cortex but also in the hippocampus, striatum, cerebellum and periphery. The rapid decline in the enhanced D-serine levels was observed in the periphery and cerebellum, whereas the injection caused a prolonged elevation of the D-serine levels in the cortex and hippocampus. The application caused a slight increase in the L-serine levels in several brain areas and periphery 3 or 6 h after the injection, whereas a significant decrease in the L-serine concentration was observed in the periphery, diencephalon and cerebellum 3 or 7 days after the injection. Because a structural abnormality and N-methyl-D-aspartate (NMDA) receptor hypofunction has been demonstrated in the cortex and hippocampus of schizophrenic subjects, D-serine treatment may offer a new therapeutic approach to diseases related to the hypofunction of NMDA receptors such as schizophrenia.
Hashimoto
Atsushi
A
Department of Pharmacology, School of Medicine, Tokai University, Isehara, Kanagawa 259-1143, Japan. hashimot@is.icc.u-tokai.ac.jp
Chiba
Sachie
S
Chiba
Yukie
Y
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D012694:Serine