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  • Title: Subchronic administration of ketamine decreases the mRNA expression of serine racemase in rat brain.
    Author: Watanabe M, Yoshikawa M, Takeyama K, Hashimoto A, Kobayashi H, Suzuki T.
    Journal: Tokai J Exp Clin Med; 2010 Dec 20; 35(4):137-43. PubMed ID: 21319044.
    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.
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