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| Research article summary (published 28 Dec 2008): |
Genetic inactivation of D-amino acid oxidase enhances extinction and reversal learning in mice.
Full Abstract
Activation of the N-methyl-D-aspartate receptor (NMDAR) glycine site has been shown to accelerate adaptive forms of learning that may benefit psychopathologies involving cognitive and perseverative disturbances. In this study, the effects of increasing the brain levels of the endogenous NMDAR glycine site agonist D-serine, through the genetic inactivation of its catabolic enzyme D-amino acid oxidase (DAO), were examined in behavioral tests of learning and memory. In the Morris water maze task (MWM), mice carrying the hypofunctional Dao1(G181R) mutation demonstrated normal acquisition of a single platform location but had substantially improved memory for a new target location in the subsequent reversal phase. Furthermore, Dao1(G181R) mutant animals exhibited an increased rate of extinction in the MWM that was similarly observed following pharmacological administration of D-serine (600 mg/kg) in wild-type C57BL/6J mice. In contextual and cued fear conditioning, no alterations were found in initial associative memory recall; however, extinction of the contextual fear memory was facilitated in mutant animals. Thus, an augmented level of D-serine resulting from reduced DAO activity promotes adaptive learning in response to changing conditions. The NMDAR glycine site and DAO may be promising therapeutic targets to improve cognitive flexibility and inhibitory learning in psychiatric disorders such as schizophrenia and anxiety syndromes.
Author information
Author/s: Labrie, Viviane (V); Duffy, Steven (S); Wang, Wei (W); Barger, Steven W (SW); Baker, Glen B (GB); Roder, John C (JC);
Affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5G 1X5, Canada. labrie(-atsign-)lunenfeld.ca
Grants: P01AG12411 (Agency:NIA NIH HHS)
Journal and publication information
Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Journal: Learning & memory (Cold Spring Harbor, N.Y.) (Learn Mem), published in United States. (Language: eng)
Reference: 2009-Jan; vol 16 (issue 1) : pp 28-37
Dates: Created 2009/01/01; Completed 2009/03/03;
PMID: 19117914, status: MEDLINE (last retrieval date: 3/10/2009, IMS Date: 10 Mar 2009 00:00:00)
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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