title: Subchronic administration of ketamine decreases the mRNA expression of serine racemase in rat brain.
abstract: The behavioral impairment produced by ketamine represents a pharmacological model for some aspects of schizophrenia such as positive, negative, and cognitive symptoms. Despite the multiple properties of ketamine, the main mechanism for its psychomimetic and anesthetic effect involves NMDA receptor system. Present study examined whether subchronic administration of ketamine at the subanesthetic doses (50 mg/kg) induces changes of behavior analogous to those observed in schizophrenia and the gene expressions of the enzymes for D-serine, an endogenous co-agonist for the NMDA-glycine site, in rat brain. Administration of ketamine daily for 14 consecutive days increased stereotyped behavior, ataxia and locomotion. The levels of serine racemase mRNAs in forebrain areas significantly decreased after subchronic administration of ketamine. In contrast, subchronic ketamine administration produced a significant increase in the mRNA expression of D-amino acid oxidase in the midbrain. These findings suggest that there is a relationship between the gene expression of the D-serine-related enzymes and the blockade of the NMDA receptors.
authors.affiliation: Department of Anesthesiology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Takeyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hashimoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000201:enzymology*; D003605:D-Amino-Acid Oxidase / Q000235:genetics / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D019998:Racemases and Epimerases / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D000099300:Serine Racemase
chemical_list: D003605:D-Amino-Acid Oxidase; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D012333:RNA, Messenger; D019998:Racemases and Epimerases; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D000099300:Serine Racemase