Effects of D-cycloserine on extinction of conditioned freezing.
Abstract
The present study tested the prediction that D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist, would facilitate extinction of conditioned freezing in male Sprague-Dawley rats. Rats received 5 light-shock pairings (conditioning). The following day, rats received 6 light-alone presentations (extinction training). Twenty-four hours later, rats received 1 light-alone presentation (test). Subcutaneous DCS injection before or after extinction training significantly enhanced extinction, and the dose-response curve for this effect was linear. Increasing the delay of DCS administration after extinction training led to a linear decrease in the facilitatory effect. The effect of systemic administration was replicated by intra-basolateral amygdala infusion. These results suggest that DCS facilitates extinction of conditioned freezing by acting on consolidation processes partly mediated by the basolateral amygdala.
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D-cycloserine (DCS) enhances the acquisition of the extinction memory.
“administration of the NMDAR partial agonist D-cycloserine (DCS) enhances the acquisition of the extinction memory”
From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Ledgerwood et al., 2003
DCS has no effect when administered after re-exposure in rodents.
“with no effect when administered after re-exposure in rodents (Ledgerwood et al., 2003; Lee et al., 2006a)”
From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Ledgerwood et al., 2003
Preclinical research has demonstrated that DCS facilitates extinction learning and memory in rodent models.
“Preclinical research has demonstrated that DCS facilitates extinction learning and memory in rodent models (Davis et al, 2006; Ledgerwood et al, 2003; Walker et al, 2002).”
From D-cycloserine augmentation of exposure therapy for post-traumatic stress disorder: a pilot randomized clinical trial (2014) · cites this paper as Ledgerwood et al, 2003
Weekly dosing administered 90 min before exposure sessions has been effective in multiple animal and human fear extinction studies.
“We chose weekly dosing, administered 90 min before exposure sessions, as this regimen has been effective in multiple animal and human fear extinction studies (Ledgerwood et al, 2003; Ressler et al, 2004; Walker et al, 2002)”
From D-cycloserine augmentation of exposure therapy for post-traumatic stress disorder: a pilot randomized clinical trial (2014) · cites this paper as Ledgerwood et al, 2003
Administration of D-cycloserine (DCS), a partial agonist of the NMDA receptor involved in long-term potentiation, facilitates extinction of conditioned fear.
“administration of D-cycloserine (DCS), a partial agonist of the NMDA receptor involved in long-term potentiation (a cellular model of learning), facilitates extinction (e.g., Walker, Ressler, Lu, & Davis, 2002; Ledgerwood, Richardson, & Cranney, 2003).”
From D-cycloserine facilitates context-specific fear extinction learning (2008) · cites this paper as Ledgerwood, Richardson, & Cranney, 2003
Our results are generally in agreement with Walker et al (2002) and Ledgerwood et al (2003) that DCS systemic administration enhanced the extinction of conditioned fear.
“Our results are generally in agreement with the results of Walker et al (2002) and Ledgerwood et al (2003), in which DCS systemic administration enhanced the extinction of conditioned fear.”
From Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD (2008) · cites this paper as Ledgerwood et al (2003)
The NMDA receptor plays a critical role in fear extinction.
“Likewise, though the molecular mechanism of contextual fear extinction remains to be precisely determined, the N-methyl-D-aspartate (NMDA) receptor appears to play a critical role in fear extinction (Falls et al, 1992;Ledgerwood et al, 2003Ledgerwood et al, , 2004Ledgerwood et al, , 2005;;Rodrigues et al, 2001;Santini et al, 2001;Walker et al, 2002).”
From Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD (2008) · cites this paper as Ledgerwood et al, 2003
The DCS dose (15 mg/kg per rat) was chosen on the basis of other behavioral studies.
“The DCS dose (15 mg/kg per rat) was chosen on the basis of the results of other behavioral studies (Ledgerwood et al, 2003(Ledgerwood et al, , 2005;;Walker et al, 2002).”
From Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD (2008) · cites this paper as Ledgerwood et al, 2003
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- Authors
- Ledgerwood, L., Richardson, R., & Cranney, J.
- Affiliations
- UNSW Sydney (AU)
- Venue
- Behavioral Neuroscience
- Published
- 2003
- Volume
- 117
- Issue
- 2
- Pages
- 341-349
- ISSN
- 0735-7044 (ISSN-L)
- 1939-0084
- OpenAlex
- W2129939370
- Cited by
- 388
- References
- 46
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 3 · 2022: 9 · 2021: 11 · 2020: 9 · 2019: 12 · 2018: 16 · 2017: 19 · 2016: 10 · 2015: 16 · 2014: 18 · 2013: 28 · 2012: 25
- FWCI
- 8.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioral Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- D-cycloserine, extinction, conditioned freezing, NMDA receptor agonist, basolateral amygdala, memory consolidation, fear extinction, dose-response relationship
- MeSH terms
- Amygdala, Analysis of Variance, Animals, Brain Mapping, Conditioning, Psychological, Cycloserine, Dose-Response Relationship, Drug, Drug Administration Routes, Extinction, Psychological, Male, Reflex, Startle, Time Factors, Rats, Sprague-Dawley, Excitatory Amino Acid Agonists, Rats
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