title: Long-term treatment with morphine increases the D-serine content in the rat brain by regulating the mRNA and protein expressions of serine racemase and D-amino acid oxidase.
abstract: Recent studies indicate that an endogenous co-agonist for an N-methyl-D-aspartate (NMDA) receptor-related glycine site, D-serine, is synthesized by serine racemase and is metabolized by D-amino acid oxidase (DAO) and that acute treatment with morphine augments the gene expression of serine racemase and DAO in rat brain. To further elucidate the mechanism underlying the activation of NMDA receptors following chronic opioid administration, we have evaluated the effects of the chronic administration of morphine on the mRNA and protein expressions of serine racemase and DAO and on the contents of D-serine in several areas of the rat brain. Repeated administration of morphine for 30 days produced a significant augmentation of both the mRNA and protein expressions of serine racemase in all the brain regions, whereas no significant change in the protein expression of DAO was observed in all the brain regions. Furthermore, the chronic administration caused a slight but significant elevation in the concentration of D-serine in the cortex, striatum, and hippocampus. These results indicate the elevated D-serine level following the chronic morphine treatment could at least in part be involved in the activation of NMDA receptors via the glycine site.
authors.affiliation: Department of Clinical Pharmacology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Shinomiya
authors.forename: Naoko
authors.initials: N
authors.lastname: Takayasu
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukamoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Oka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hashimoto
mesh_terms: D000701:Analgesics, Opioid; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D003605:D-Amino-Acid Oxidase / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D019998:Racemases and Epimerases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000378:metabolism*; D013995:Time; D000099300:Serine Racemase
chemical_list: D000701:Analgesics, Opioid; D003605:D-Amino-Acid Oxidase; D009020:Morphine; D012333:RNA, Messenger; D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase