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PMID: 11896173 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of D-cycloserine as assessed with fear-potentiated startle in rats.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 22 ·No. 6 ·2002-03-15 ·Pages 2343-51

Walker DL, Ressler KJ, Lu KT, Davis M

Abstract

NMDA receptor antagonists block conditioned fear extinction when injected systemically and also when infused directly into the amygdala. Here we evaluate the ability of D-cycloserine (DCS), a partial agonist at the strychnine-insensitive glycine-recognition site on the NMDA receptor complex, to facilitate conditioned fear extinction after systemic administration or intra-amygdala infusions. Rats received 10 pairings of a 3.7 sec light and a 0.4 mA footshock (fear conditioning). Fear-potentiated startle (increased startle in the presence vs the absence of the light) was subsequently measured before and after 30, 60, or 90 presentations of the light without shock (extinction training). Thirty non-reinforced light presentations produced modest extinction, and 60 or 90 presentations produced nearly complete extinction (experiment 1). DCS injections (3.25, 15, or 30 mg/kg) before 30 non-reinforced light exposures dose-dependently enhanced extinction (experiment 2) but did not influence fear-potentiated startle in rats that did not receive extinction training (experiment 3). These effects were blocked by HA-966, an antagonist at the glycine-recognition site (experiment 4). Neither DCS nor HA-966 altered fear-potentiated startle when injected before testing (experiment 5). The effect of systemic administration was mimicked by intra-amygdala DCS (10 microg/side) infusions (experiment 6). These results indicate that treatments that promote NMDA receptor activity after either systemic or intra-amygdala administration promote the extinction of conditioned fear.

MeSH Terms
Acoustic Stimulation Amygdala/drug effects,physiology Animals Behavior, Animal/drug effects Catheterization Conditioning, Classical/drug effects Cycloserine/administration & dosage Dose-Response Relationship, Drug Electroshock Excitatory Amino Acid Agonists/pharmacology Extinction, Psychological/drug effects,physiology Fear/drug effects,physiology Infusions, Parenteral Male Photic Stimulation Pyrrolidinones/pharmacology Rats Rats, Sprague-Dawley Reflex, Startle/drug effects,physiology Stereoisomerism
Chemicals
Excitatory Amino Acid Agonists Pyrrolidinones Cycloserine 1-hydroxy-3-amino-2-pyrrolidone
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Walker David L
Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia 30322, USA. dlwalke@emory.edu
Ressler Kerry J
Lu Kwok-Tung
Davis Michael
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Email
dlwalke@emory.edu
Published
2002-03-15
Pages
2343-51
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6758267
Subset
IM
Grants
NIMH NIH HHS · MH 58922 · United States
NIMH NIH HHS · R01 MH047840 · United States
NIMH NIH HHS · MH 52384 · United States
NIMH NIH HHS · R01 MH059906 · United States
NIMH NIH HHS · R37 MH047840 · United States
NIMH NIH HHS · P50 MH052384 · United States
NIMH NIH HHS · MH 59906 · United States
NIMH NIH HHS · MH 57250 · United States
NIMH NIH HHS · P50 MH058922 · United States
NIMH NIH HHS · MH 47840 · United States
NIMH NIH HHS · R01 MH057250 · United States
External Links
PubMed source PMC Full Text View journal details
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