PMID- 19117914
OWN - NLM
STAT- MEDLINE
DCOM- 20090303
LR  - 20211020
IS  - 1549-5485 (Electronic)
IS  - 1072-0502 (Print)
IS  - 1072-0502 (Linking)
VI  - 16
IP  - 1
DP  - 2009 Jan
TI  - Genetic inactivation of D-amino acid oxidase enhances extinction and reversal 
      learning in mice.
PG  - 28-37
LID - 10.1101/lm.1112209 [doi]
AB  - 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.
FAU - Labrie, Viviane
AU  - Labrie V
AD  - Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5G 1X5, 
      Canada. labrie@lunenfeld.ca
FAU - Duffy, Steven
AU  - Duffy S
FAU - Wang, Wei
AU  - Wang W
FAU - Barger, Steven W
AU  - Barger SW
FAU - Baker, Glen B
AU  - Baker GB
FAU - Roder, John C
AU  - Roder JC
LA  - eng
GR  - P01 AG012411/AG/NIA NIH HHS/United States
GR  - P01AG12411/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20081230
PL  - United States
TA  - Learn Mem
JT  - Learning & memory (Cold Spring Harbor, N.Y.)
JID - 9435678
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 452VLY9402 (Serine)
RN  - EC 1.4.3.3 (D-Amino-Acid Oxidase)
SB  - IM
MH  - Animals
MH  - Brain/*physiology
MH  - D-Amino-Acid Oxidase/*genetics
MH  - Extinction, Psychological/*physiology
MH  - Maze Learning/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Reversal Learning/*physiology
MH  - Serine/pharmacology
PMC - PMC2632856
EDAT- 2009/01/02 09:00
MHDA- 2009/03/04 09:00
PMCR- 2010/01/01
CRDT- 2009/01/02 09:00
PHST- 2009/01/02 09:00 [entrez]
PHST- 2009/01/02 09:00 [pubmed]
PHST- 2009/03/04 09:00 [medline]
PHST- 2010/01/01 00:00 [pmc-release]
AID - 16/1/28 [pii]
AID - 10.1101/lm.1112209 [doi]
PST - epublish
SO  - Learn Mem. 2008 Dec 30;16(1):28-37. doi: 10.1101/lm.1112209. Print 2009 Jan.