PMID- 20303474
OWN - NLM
STAT- MEDLINE
DCOM- 20101025
LR  - 20131121
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Linking)
VI  - 67
IP  - 12
DP  - 2010 Jun 15
TI  - The N-methyl-D-aspartate receptor co-agonist D-cycloserine facilitates 
      declarative learning and hippocampal activity in humans.
PG  - 1205-11
LID - 10.1016/j.biopsych.2010.01.022 [doi]
AB  - BACKGROUND: The N-methyl-D-aspartate receptor (NMDAR) is critical for 
      learning-related synaptic plasticity in amygdala and hippocampus. As a 
      consequence, there is considerable interest in drugs targeting this receptor to 
      help enhance amygdala- and hippocampus-dependent learning. A promising candidate 
      in this respect is the NMDAR glycine-binding site partial agonist D-cycloserine 
      (DCS). Accumulating clinical evidence indicates the efficacy of DCS in the 
      facilitation of amygdala-dependent fear extinction learning in patients with 
      phobic, social anxiety, panic, and obsessive-compulsive disorder. An important 
      unresolved question though is whether the use of DCS can also facilitate 
      hippocampus-dependent declarative learning in healthy people as opposed to being 
      restricted to the fear memory domain. METHODS: In the present study, we 
      investigated whether or not DCS can facilitate hippocampus-dependent declarative 
      learning. We have therefore combined functional magnetic resonance imaging with 
      two different declarative learning tasks and cytoarchitectonic probabilistic 
      mapping of the hippocampus and its major subdivisions in 40 healthy volunteers 
      administered either a 250 mg single oral dose of DCS or a placebo. RESULTS: We 
      found that DCS facilitates declarative learning as well as blood-oxygen level 
      dependent activity levels in the probabilistically defined cornu ammonis region 
      of the hippocampus. The absence of activity changes in visual control areas 
      underscores the specific action of DCS in the hippocampal cornu ammonis region. 
      CONCLUSIONS: Our findings highlight NMDAR glycine-binding site partial agonism as 
      a promising pharmacological mechanism for facilitating declarative learning in 
      healthy people.
FAU - Onur, Oezguer A
AU  - Onur OA
AD  - Department of Psychiatry, University of Bonn, Bonn, Germany.
FAU - Schlaepfer, Thomas E
AU  - Schlaepfer TE
FAU - Kukolja, Juraj
AU  - Kukolja J
FAU - Bauer, Andreas
AU  - Bauer A
FAU - Jeung, Haang
AU  - Jeung H
FAU - Patin, Alexandra
AU  - Patin A
FAU - Otte, David-Marian
AU  - Otte DM
FAU - Shah, N Jon
AU  - Shah NJ
FAU - Maier, Wolfgang
AU  - Maier W
FAU - Kendrick, Keith M
AU  - Kendrick KM
FAU - Fink, Gereon R
AU  - Fink GR
FAU - Hurlemann, Rene
AU  - Hurlemann R
LA  - eng
SI  - ClinicalTrials.gov/NCT00980408
GR  - Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20100320
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 95IK5KI84Z (Cycloserine)
SB  - IM
MH  - Adult
MH  - Cycloserine/*pharmacology
MH  - Female
MH  - Hippocampus/*drug effects/physiology
MH  - Humans
MH  - Learning/*drug effects/physiology
MH  - Magnetic Resonance Imaging/methods
MH  - Male
MH  - Photic Stimulation/methods
MH  - Psychomotor Performance/*drug effects/physiology
MH  - Receptors, N-Methyl-D-Aspartate/*agonists
EDAT- 2010/03/23 06:00
MHDA- 2010/10/26 06:00
CRDT- 2010/03/23 06:00
PHST- 2009/11/10 00:00 [received]
PHST- 2010/01/12 00:00 [revised]
PHST- 2010/01/22 00:00 [accepted]
PHST- 2010/03/23 06:00 [entrez]
PHST- 2010/03/23 06:00 [pubmed]
PHST- 2010/10/26 06:00 [medline]
AID - S0006-3223(10)00064-8 [pii]
AID - 10.1016/j.biopsych.2010.01.022 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2010 Jun 15;67(12):1205-11. doi: 10.1016/j.biopsych.2010.01.022. 
      Epub 2010 Mar 20.