Genetic Inactivation of D-Amino Acid Oxidase Enhances Extinction and Reversal Learning in Mice

Autor/inn/en	Labrie, Viviane; Duffy, Steven; Wang, Wei; Barger, Steven W.; Baker, Glen B.; Roder, John C.
Titel	Genetic Inactivation of D-Amino Acid Oxidase Enhances Extinction and Reversal Learning in Mice
Quelle	In: Learning & Memory, 16 (2009) 1, S.28-37 (10 Seiten) PDF als Volltext Verfügbarkeit
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	1072-0502
DOI	10.1101/lm.1112209
Schlagwörter	Animals; Schizophrenia; Genetics; Memory; Fear; Learning Processes; Psychopathology; Brain; Drug Use; Task Analysis; Cues; Anxiety; Mental Disorders + Suchen Sie Ihr Suchwort? Animal; Tier; Tiere; Schizophrenie; Humangenetik; Gedächtnis; Furcht; Learning process; Lernprozess; Psychopathologie; Gehirn; Drug consumption; Substance abuse; Drogenkonsum; Aufgabenanalyse; Stichwort; Angst; Mental illness; Geisteskrankheit
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[superscript 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, "Dao[superscript 1G181R]" 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. (As Provided).
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Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2017/4/10