PMID- 19855841
OWN - NLM
STAT- MEDLINE
DCOM- 20100312
LR  - 20220309
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 4
IP  - 10
DP  - 2009 Oct 26
TI  - A NMDA receptor antagonist, MK-801 impairs consolidating extinction of auditory 
      conditioned fear responses in a Pavlovian model.
PG  - e7548
LID - 10.1371/journal.pone.0007548 [doi]
LID - e7548
AB  - BACKGROUND: In auditory fear conditioning, repeated presentation of the tone in 
      the absence of shock leads to extinction of the acquired fear responses. The 
      glutamate N-methyl-D-aspartate receptor (NMDAR) is thought to be involved in the 
      extinction of the conditioned fear responses, but its detailed role in initiating 
      and consolidating or maintaining the fear extinction memory is unclear. Here we 
      investigated this issue by using a NMDAR antagonist, MK-801. METHODS/MAIN 
      FINDINGS: The effects of immediate (beginning at 10 min after the conditioning) 
      and delayed (beginning at 24 h after conditioning) extinctions were first 
      compared with the finding that delayed extinction caused a better and 
      long-lasting (still significant on the 20(th) day after extinction) depression on 
      the conditioned fear responses. In a second experiment, MK-801 was 
      intraperitoneally (i.p.) injected at 40 min before, 4 h or 12 h after the delayed 
      extinction, corresponding to critical time points for initiating, consolidating 
      or maintaining the fear extinction memory. i.p. injection of MK-801 at either 40 
      min before or 4 h after delayed extinction resulted in an impairment of 
      initiating and consolidating fear extinction memory, which caused a long lasting 
      increased freezing score that was still significant on the 7th day after 
      extinction, compared with extinction group. However, MK-801 administered at 12 h 
      after the delayed extinction, when robust consolidation has been occurred and 
      stabilized, did not affect the established extinction memory. Furthermore, the 
      changed freezing behaviors was not due to an alteration in general anxiety 
      levels, since MK-801 treatment had no effect on the percentage of open-arm time 
      or open-arm entries in an Elevated Plus Maze (EPM) task. 
      CONCLUSIONS/SIGNIFICANCE: Our data suggested that the activation of NMDARs plays 
      important role in initiation and consolidation but not maintenance of fear 
      extinction memory. Together with the fact that NMDA receptor is very important 
      for memory, our data added experimental evidence to the concept that the 
      extinction of conditioned fear responses is a procedure of initiating and 
      consolidating new memory other than simply "erasing" the fear memory.
FAU - Liu, Jun-Li
AU  - Liu JL
AD  - Department of Teaching and Training, Fourth Military Medical University, Xi'an, 
      People's Republic of China.
FAU - Li, Min
AU  - Li M
FAU - Dang, Xiao-Rong
AU  - Dang XR
FAU - Wang, Zheng-Hong
AU  - Wang ZH
FAU - Rao, Zhi-Ren
AU  - Rao ZR
FAU - Wu, Sheng-Xi
AU  - Wu SX
FAU - Li, Yun-Qing
AU  - Li YQ
FAU - Wang, Wen
AU  - Wang W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091026
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
SB  - IM
MH  - Animals
MH  - Anxiety/drug therapy
MH  - Behavior, Animal
MH  - Conditioning, Classical/*drug effects
MH  - Conditioning, Psychological/drug effects
MH  - Dizocilpine Maleate/*pharmacology
MH  - Extinction, Psychological/drug effects
MH  - Fear/*drug effects
MH  - Humans
MH  - Male
MH  - Memory/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Time Factors
PMC - PMC2763217
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/10/27 06:00
MHDA- 2010/03/13 06:00
PMCR- 2009/10/26
CRDT- 2009/10/27 06:00
PHST- 2009/03/23 00:00 [received]
PHST- 2009/09/22 00:00 [accepted]
PHST- 2009/10/27 06:00 [entrez]
PHST- 2009/10/27 06:00 [pubmed]
PHST- 2010/03/13 06:00 [medline]
PHST- 2009/10/26 00:00 [pmc-release]
AID - 09-PONE-RA-09364R2 [pii]
AID - 10.1371/journal.pone.0007548 [doi]
PST - epublish
SO  - PLoS One. 2009 Oct 26;4(10):e7548. doi: 10.1371/journal.pone.0007548.