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000009820 084__ $$2WoS$$aNeurosciences
000009820 084__ $$2WoS$$aPsychiatry
000009820 1001_ $$0P:(DE-Juel1)131736$$aOnur, O.A.$$b0$$uFZJ
000009820 245__ $$aThe N-Methyl-D-Aspartate Receptor Co-agonist D-Cycloserine Facilitates Declarative Learning and Hippocampal Activity in Humans
000009820 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2010
000009820 300__ $$a1205 - 1211
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000009820 440_0 $$011361$$aBiological Psychiatry$$v67$$x0006-3223$$y12
000009820 500__ $$aRH was supported by a German Research Foundation Grant (HU1302/2-2) and by a Starting Independent Researcher Grant jointly provided by the Ministry of Innovation, Science, Research and Technology of the State of North Rhine-Westphalia and the University of Bonn. KMK was supported by the Biotechnology and Biological Sciences Research Council.
000009820 520__ $$aThe 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.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.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.Our findings highlight NMDAR glycine-binding site partial agonism as a promising pharmacological mechanism for facilitating declarative learning in healthy people.
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000009820 65320 $$2Author$$aCognitive enhancement
000009820 65320 $$2Author$$aD-cycloserine
000009820 65320 $$2Author$$adeclarative learning
000009820 65320 $$2Author$$afMRI
000009820 65320 $$2Author$$ahippocampus
000009820 65320 $$2Author$$amemory
000009820 65320 $$2Author$$aNMDA receptor
000009820 650_2 $$2MeSH$$aAdult
000009820 650_2 $$2MeSH$$aCycloserine: pharmacology
000009820 650_2 $$2MeSH$$aFemale
000009820 650_2 $$2MeSH$$aHippocampus: drug effects
000009820 650_2 $$2MeSH$$aHippocampus: physiology
000009820 650_2 $$2MeSH$$aHumans
000009820 650_2 $$2MeSH$$aLearning: drug effects
000009820 650_2 $$2MeSH$$aLearning: physiology
000009820 650_2 $$2MeSH$$aMagnetic Resonance Imaging: methods
000009820 650_2 $$2MeSH$$aMale
000009820 650_2 $$2MeSH$$aPhotic Stimulation: methods
000009820 650_2 $$2MeSH$$aPsychomotor Performance: drug effects
000009820 650_2 $$2MeSH$$aPsychomotor Performance: physiology
000009820 650_2 $$2MeSH$$aReceptors, N-Methyl-D-Aspartate: agonists
000009820 650_7 $$00$$2NLM Chemicals$$aReceptors, N-Methyl-D-Aspartate
000009820 650_7 $$068-41-7$$2NLM Chemicals$$aCycloserine
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000009820 7001_ $$0P:(DE-HGF)0$$aSchlaepfer, T.E.$$b1
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