D-cycloserine facilitates context-specific fear extinction learning
Open accessAbstract
D-cycloserine (DCS) may facilitate fear extinction learning, but the behavioral consequences and mechanisms behind this effect are not well understood at present. In this paper, we re-analyze data from previously reported null result experiments and find that rats showing above-median extinction learning during DCS treatment benefited from the drug, whereas rats showing below-median (and in this case little) extinction learning did not. Two additional experiments found that DCS facilitated extinction learning when specifically combined with a moderate, but not a small, number of extinction trials. DCS thus facilitates extinction learning only if the behavioral procedure first engages the extinction learning process. The benefits of the drug, however, were specific to the context in which extinction was learned--i.e., DCS did not prevent or influence the renewal of fear observed when the extinguished cue was tested in the original conditioning context.
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Written from the paper’s full text.
TL;DR
D-cycloserine (DCS) facilitated fear extinction only when the extinction procedure first engaged learning: rats that learned some extinction during the drug session benefited, and DCS helped with 12 but not 2 extinction trials. The benefit was context-specific and did not reduce renewal of fear in the original conditioning context.
Key findings
- In Experiment 1, a median split showed that rats above the median learned extinction during the DCS session, with a significant decrease in suppression across trial blocks, F(1, 22) = 54.80, whereas below-median rats did not, F(1, 22) < 1. DCS facilitated later test extinction only in above-median rats (group × block interaction, F(3, 66) = 2.95; significant on the second block, F(1, 22) = 4.73), with no DCS effect in below-median rats.
- In Experiment 2A, DCS facilitated extinction in the 12-trial group, F(1, 15) = 4.76, but not in the 2-trial group, F(1, 15) < 1. In Experiment 2B, the 12-trial DCS effect was F(1, 15) = 3.87, p = .03, one-tailed; pooled across 2A and 2B it was F(1, 31) = 8.69, two-tailed p = .006, while the 2-trial group did not approach significance, F < 1.
- DCS did not influence renewal. In Experiment 2A, renewal testing in Context A showed a significant difference between tests, F(1, 15) = 14.58, with no drug effect or interaction, Fs ≤ 2.01. In Experiment 2B, there were no drug effects or interactions, Fs ≤ 1.71, while freezing increased in Context A, F(1, 15) = 3.97, p = .03, one-tailed; pooled across 2A and 2B, F(1, 31) = 14.41, two-tailed p = .001.
Methods
- Experiment 1 used 48 female Wistar rats in a conditioned suppression procedure. Rats received fear conditioning in Context A, then four CS-alone extinction trials in Context B with DCS 30 mg/kg or saline injected 15 min before the session; tests occurred in Context B, and a median split on drug-session suppression ratios classified above- versus below-median extinction learning.
- Experiments 2A and 2B used 64 naive female Wistar rats (32 each). Rats received fear conditioning with two CSs in Context A; one CS was extinguished with saline in Context B and the other with DCS in Context C, with either 12 or 2 extinction trials and DCS doses of 15 or 30 mg/kg. Freezing was scored every 2 s, with interobserver correlations of r(62) = .97 and .92 for Experiments 2A and 2B; tests occurred in the extinction contexts and then in Context A for renewal.
- Statistical analysis used ANOVA with rejection criterion p < .05.
Limitations
- The paper states that Experiment 1 was correlational and could have been controlled by an unidentified third variable; Experiment 2 was designed to isolate the combination of DCS and CS re-exposure experimentally.
- The paper notes that its results did not replicate Lee et al.’s (2006) finding that DCS increased fear with minimal extinction training, and it lists procedural differences including number of CS re-exposures, session duration, and whether re-exposure occurred in a different context.
- Evident from the text: the experiments used only female Wistar rats, specific fear-conditioning preparations (conditioned suppression and conditioned freezing), limited DCS doses, and particular trial numbers, so the boundary conditions may not generalize beyond these procedures.
Model-written summary. Check it against the paper before relying on it.
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Cites
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Claims the paper makes
0 of 14 cited sources checked · 0 supported · 0 flagged
- Findingown data
In Experiment 2B, freezing increased when the rats were returned to and tested in Context A.
“Freezing increased when the rats were returned to and tested in Context A, F (1,15) = 3.97, p = .03, one-tailed.”
Quote in the paperSubstantial claim - Findingown data
In Experiment 2B, DCS did not influence the strength of the renewal effect observed when animals were tested with the CSs in Context A.
“As in Experiment 2, DCS did not influence the strength of the renewal effect observed when the animals were tested with the CSs in Context A.”
Quote in the paperSubstantial claim - Findingown data
In Experiment 2A, DCS did not influence the strength of the renewal effect observed when animals were tested with the CSs in Context A.
“Although these results indicate that DCS does facilitate extinction (loss of freezing) in rats given the larger number of trials, DCS did not influence the strength of the renewal effect observed when the animals were tested with the CSs in Context A.”
Quote in the paperSubstantial claim - Findingown data
DCS did not prevent or influence the renewal of fear observed when the extinguished cue was tested in the original conditioning context.
“DCS did not prevent or influence the renewal of fear observed when the extinguished cue was tested in the original conditioning context.”
Quote in the paperSubstantial claim- Rests on an assumption: The renewal test had sufficient sensitivity or power to detect a DCS effect on renewal if such an effect were present.
- Findingown data
Whether extinction was combined with DCS or saline, there was equivalent renewal of fear when the CS was removed from the extinction context and tested in the original conditioning context.
“whether extinction was combined with DCS or saline, there was equivalent renewal of fear when the CS was removed from the extinction context and tested in the original conditioning context (Experiment 2).”
Quote in the paperSubstantial claim- Rests on an assumption: The renewal test had sufficient sensitivity or power to detect a DCS effect on renewal if such an effect were present.
- Findingown data
The present experiments did not replicate Lee et al.'s (2006) finding that DCS increased fear when administered with minimal extinction training.
“The present experiments did not replicate Lee et al.’s (2006) finding that DCS increased fear, rather than decreased fear, when it was administered with minimal extinction training.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Lee et al.’s (2006) source
Not checked in the free run.
- Premisecitation
Weber et al. (2007) found that only rats that had demonstrably learned some extinction benefited from DCS.
“When they separated subjects that had learned some extinction from those that had not, only the rats that had demonstrably learned some extinction benefited from the DCS.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Weber, Hart, and Richardson (2007)
Not checked in the free run.
- Interpretationown data
DCS facilitates extinction learning only if the behavioral procedure first engages the extinction learning process.
“DCS thus facilitates extinction learning only if the behavioral procedure first engages the extinction learning process.”
Quote in the paperSubstantial claim- Rests on an assumption: DCS is present in the brain during the extinction session when administered 15 minutes before the session.
- Premisecitation
In humans, DCS administration can facilitate the loss of fear resulting from exposure that causes incomplete fear loss in controls.
“In humans, DCS administration can likewise facilitate the loss of fear resulting from exposure that causes incomplete fear loss in controls (acrophobia: Ressler, Rothbaum, Tannenbaum, Anderson, Graap, Zimand, Hodges, & Davis, 2004; social phobia: Guastella, Richardson, Lovibond, Rapee, Gaston, Mitchell, & Dadds, 2008; Hofmann, Meuret, Smits, Simon, Pollack, Eisenmenger, Shiekh, & Otto, 2006;”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Ressler, Rothbaum, Tannenbaum, Anderson, Graap, Zimand, Hodges, & Davis, 2004 source
Not checked in the free run.
- cites Guastella, Richardson, Lovibond, Rapee, Gaston, Mitchell, & Dadds, 2008 source
Not checked in the free run.
- cites Hofmann, Meuret, Smits, Simon, Pollack, Eisenmenger, Shiekh, & Otto, 2006 source
Not checked in the free run.
- Interpretationown data
The benefits of DCS are specific to the context in which extinction was learned.
“The benefits of the drug, however, were specific to the context in which extinction was learned—i.e., DCS did not prevent or influence the renewal of fear observed when the extinguished cue was tested in the original conditioning context.”
Quote in the paperSubstantial claim - Premisecitation
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).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning
DCS facilitates error correction rather than error detection in extinction learning.
“The present results imply that DCS facilitates error correction rather than error detection, which could presumably influence extinction as early as the first extinction trial.”
Quote in the paperSubstantial claim - Study design and conductcitation
The within-subject comparison of fear of a CS extinguished with DCS and a second CS extinguished with saline specifically isolates the role of the combination of DCS and CS re-exposure.
“Notice that the within-subject comparison of fear of a CS extinguished with DCS and a second CS extinguished with Saline specifically isolates the role of the combination of DCS and CS re-exposure (cf. Lee et al., 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Lee et al., 2006 source
Not checked in the free run.
- Study design and conductown data
The fact that the 2-trial group had the same low level of freezing during the test but still showed no DCS effect indicates that the effect of the number of extinction trials was not merely an artifact of differential levels of fear during testing.
“The fact that the 2-trial group had the same low level of freezing during the test, but still showed no DCS effect, indicates that the effect of the number of extinction trials was not merely an artifact of differential levels of fear during testing.”
Quote in the paperSubstantial claim - Interpretationown data
The equivalent renewal result replicates, in the freezing preparation, the results of Woods and Bouton (2006) in the conditioned suppression preparation.
“That result replicates, in the freezing preparation, the results of Woods and Bouton (2006) in the conditioned suppression preparation.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Woods and Bouton (2006) source
Not checked in the free run.
- Interpretationown data
The effect of DCS is to boost or enhance extinction learning that is already in progress.
“They indicate that the effect of DCS is to boost or enhance extinction learning that is already in progress.”
Quote in the paperSubstantial claim- Rests on an assumption: DCS is present in the brain during the extinction session when administered 15 minutes before the session.
- Interpretationown data
The effectiveness of DCS as a facilitator of extinction depends on the number of extinction trials.
“the effectiveness of DCS as a facilitator of extinction depends on the number of extinction trials.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Lee et al.
Not checked in the free run.
- Interpretationown data
DCS does not necessarily change the fundamental context-dependence of extinction learning.
“DCS does not necessarily change the fundamental context-dependence of extinction learning, which may leave fear vulnerable to relapse in a different context.”
Quote in the paperSubstantial claim - Study design and conductown data
There was no difference between the groups in their lever pressing rates during the 60 s period before each CS during the Drug and Test sessions in Experiment 1.
“There was no difference between the groups in their lever pressing rates during the 60 s period before each CS during the Drug and Test sessions.”
Quote in the paperNot a substantial claim - Interpretationown data
When DCS is effective at facilitating extinction, its effects might not transfer to the original conditioning context.
“when DCS is effective at facilitating extinction, its effects might not transfer to the original conditioning context.”
Quote in the paperSubstantial claim - Interpretationreasoning
DCS apparently has an effect once extinction learning has begun.
“DCS apparently has an effect once extinction learning has begun.”
Quote in the paperSubstantial claim
- May combine two claims. 6
- Classified as probably not a substantial claim. 3
May combine two claims.
Findingown dataIn Experiment 1, rats showing above-median extinction learning during DCS treatment benefited from the drug, whereas rats showing below-median extinction learning did not.
“rats showing above-median extinction learning during DCS treatment benefited from the drug, whereas rats showing below-median (and in this case little) extinction learning did not.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn Experiment 1, rats above the median learned some extinction during the drug session, as indicated by a significant decrease in suppression across trial blocks, whereas rats below the median did not.
“rats that were above the median learned some extinction during the drug session, as indicated by a significant decrease in suppression across the trial blocks, F(1, 22) = 54.80, whereas rats below the median did not, F(1, 22) < 1.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn Experiment 2, DCS facilitated extinction learning when combined with a moderate number of extinction trials but not with a small number of extinction trials.
“Two additional experiments found that DCS facilitated extinction learning when specifically combined with a moderate, but not a small, number of extinction trials.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn two unpublished experiments, DCS had no demonstrable effect on extinction learning.
“In two unpublished experiments, DCS had no demonstrable effect on extinction learning.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Woods and Bouton (2006) source
Not checked in the free run.
May combine two claims.
PremisecitationWoods and Bouton (2006) found that although DCS facilitated fear loss in extinction, it did not weaken the renewal effect.
“Woods and Bouton (2006) found that although DCS facilitated fear loss in extinction, it did not weaken the renewal effect.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Woods and Bouton (2006) source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationLee et al. (2006) suggested that DCS enhanced memory reconsolidation when combined with minimal CS exposure and enhanced extinction when combined with more CS exposure.
“They suggested that DCS enhanced memory “reconsolidation” (Nader, Schafe, & LeDoux, 2000) when it was combined with minimal CS exposure and enhanced extinction when it was combined with more.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Lee, Milton, and Everitt (2006) source
Not checked in the free run.
- cites Nader, Schafe, & LeDoux, 2000
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataThe correlations between the observers' freezing scores were r(62) = .97 and .92 for Experiments 2A and 2B.
“The correlations between the observers’ scores (each rat in both B and C) were r (62) = .97 and .92 for Experiments 2A and 2B.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
DCS is present in the brain during the extinction session when administered 15 minutes before the session.
“the effectiveness of DCS was predicted by the extent to which animals learned extinction during the drug session (while the drug was in the brain)”
The paper relies on this without support.
The renewal test had sufficient sensitivity or power to detect a DCS effect on renewal if such an effect were present.
“DCS did not influence the strength of the renewal effect observed when the animals were tested with the CSs in Context A.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Whether DCS has beneficial or detrimental effects appears linked with the sufficiency of fear learning achieved during extinction training.
“Hence, whether DCS has beneficial or detrimental effects appears to be linked with the sufficiency of fear learning achieved during (extinction) training.”
From D-cycloserine enhancement of fear extinction is specific to successful exposure sessions: evidence from the treatment of height phobia (2013) · cites this paper as [8]
Preclinical data suggest that the DCS augmentation effect is moderated by the success of the extinction trials.
“Some preclinical data suggest that the DCS augmentation effect is moderated by the success of the extinction trials.”
From D-cycloserine enhancement of fear extinction is specific to successful exposure sessions: evidence from the treatment of height phobia (2013) · cites this paper as [8]
In a re-analysis of a null-finding animal study, a significant DCS augmentation effect was seen only for animals that had demonstrated stronger extinction learning.
“Likewise, in a re-analysis of a null-finding study (3) of DCS augmentation, Bouton and colleagues (8) subsequently performed a median split of their sample based on the extinction effects during the drug session; again, a significant DCS augmentation effect was seen only for the animals that had demonstrated stronger extinction learning.”
From D-cycloserine enhancement of fear extinction is specific to successful exposure sessions: evidence from the treatment of height phobia (2013) · cites this paper as [8]
DCS augmentation in animal studies is evident only when a sufficient number of extinction trials is offered for extinction learning.
“Specifically, both Lee and colleagues (9) and Bouton and colleagues (8) found that DCS augmentation was evident only when a sufficient number of trials was offered for extinction learning.”
From D-cycloserine enhancement of fear extinction is specific to successful exposure sessions: evidence from the treatment of height phobia (2013) · cites this paper as [8]
Preclinical research indicates that the effect of DCS is to enhance whatever emotional learning has occurred; without sufficient extinction learning on drug, there is no or little beneficial outcome to enhance.
“Preclinical research indicates that the effect of DCS is to enhance whatever emotional learning has occurred; without sufficient extinction learning on drug, there is no or little beneficial outcome to enhance (8).”
From D-cycloserine enhancement of fear extinction is specific to successful exposure sessions: evidence from the treatment of height phobia (2013) · cites this paper as [8]
Statistics recomputed
Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.
- ConsistentF(1, 15) = 3.87reported p = .03 · recomputed p = .068
“F(1,15) = 3.87, p = .03”
The paper states a one-tailed test
- ConsistentF(1, 15) = 3.97reported p = .03 · recomputed p = .065
“F (1,15) = 3.97, p = .03”
The paper states a one-tailed test
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Pearce citation year differs from the reference entry
MinorThe text cites Pearce as a 1994 source, but the corresponding Pearce reference lists 2004.
“(e.g., see Bouton, 2004; Pearce, 1994; McNally & Westbrook, 2003)”
“22. Pearce JM Similarity and discrimination: A selective review and a connectionist model Psychological Review 2004 101 587 607 7984708”
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“…beneficial effects of drugs enhancing extinction memory consolidation and exposure treatment were only observed in animals (Bolkan and Lattal, 2014; Bouton et al., 2008; Weber et al., 2007) and humans who did demonstrate successful extinction learning/treatment response to cognitive-behavioural…”
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BackgroundBehavioral and neurobiological mechanisms of pavlovian and instrumental extinction learning
Bouton, M. E., Maren, S., & McNally, G. P. (2020) · Physiological Reviews · doi:10.1152/physrev.00016.2020 · Cited by 399 · see citing works
Self-citationSeeking a Spotless Mind: Extinction, Deconsolidation, and Erasure of Fear Memory
Maren, S. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.023 · Cited by 259 · see citing works
“Interestingly, there have been reports that the extinction memory acquired under DCS is less likely to exhibit recovery (e.g., reinstatement) (Ledgerwood et al., 2004), although this outcome has not been universally reported (Bouton et al., 2008; Woods and Bouton, 2006).”
BackgroundWhy behavior change is difficult to sustain
Bouton, M. E. (2014) · Preventive Medicine · doi:10.1016/j.ypmed.2014.06.010 · Cited by 322 · see citing works
“Although administering DCS during extinction can facilitate the rate at which Pavlovian fear extinction is learned (e.g., Walker et al., 2002), it does not necessarily reduce extinction's context-dependency (Bouton et al., 2008a, 2008b; Woods and Bouton, 2006).”
BackgroundSelf-citationBouton, M. E., Winterbauer, N. E., & Todd, T. P. (2012) · Behavioural Processes · doi:10.1016/j.beproc.2012.03.004 · Cited by 217 · see citing works
“(The 15 mg/kg and 30 mg/kg doses have both been effective at facilitating fear extinction in our laboratory [e.g., Bouton et al., 2008].)”
Self-citationImpaired Extinction Retention in Adolescent Rats: Effects of D-Cycloserine
McCallum, J., Kim, J. H., & Richardson, R. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.92 · Cited by 198 · see citing works
Role of inhibition in exposure therapy
Craske, M. G., Liao, B., Brown, L., & Vervliet, B. (2012) · Journal of Experimental Psychopathology · doi:10.5127/jep.026511 · Cited by 237 · see citing works
Glutamate receptors in extinction and extinction-based therapies for psychiatric illness
Myers, K. M., Carlezon, W., & Davis, M. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.88 · Cited by 175 · see citing works
Malvaez, M., Sanchis‐Segura, C., Vo, D., Lattal, K. M., & Wood, M. A. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.07.032 · Cited by 172 · see citing works
Milad, M., Rosenbaum, B. L., & Simon, N. (2014) · Behaviour Research and Therapy · doi:10.1016/j.brat.2014.08.006 · Cited by 141 · see citing works
Can fear extinction be enhanced? A review of pharmacological and behavioral findings
Fitzgerald, P. J., Seemann, J. R., & Maren, S. (2013) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2013.12.007 · Cited by 152 · see citing works
“renewed when animals were subsequently tested in the original conditioning context, suggesting that the effects of DCS were context-specific (Bouton et al., 2008; Woods and Bouton, 2006).”
BackgroundHaaker, J., Gaburro, S., Sah, A., Gartmann, N., Lonsdorf, T. B., Meier, K., Singewald, N., Pape, H.-C., Morellini, F., & Kalisch, R. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303061110 · Cited by 166 · see citing works
Renewed behavior produced by context change and its implications for treatment maintenance: A review
Podlesnik, C. A., Kelley, M. E., Jimenez‐Gomez, C., & Bouton, M. E. (2017) · Journal of Applied Behavior Analysis · doi:10.1002/jaba.400 · Cited by 148 · see citing works
Self-citationSmits, J. A. J., Rosenfield, D., Otto, M. W., Powers, M. B., Hofmann, S. G., Telch, M. J., Pollack, M. H., & Tart, C. D. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.12.009 · Cited by 142 · see citing works
“(8) found that DCS augmentation was evident only when a sufficient number of trials was offered for extinction learning.”
InfluentialLee, J. L. C., Bertoglio, L. J., Guimarães, F. S., & Stevenson, C. W. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13724 · Cited by 140 · see citing works
“Furthermore, given that pharmacological enhancement of extinction is usually dependent upon appreciable extinction-mediated memory reduction (Weber et al., 2007; Bouton et al., 2008), and there was no evidence for any such reduction in the CBD study (Parker et al.”
BackgroundIndividual differences in recovery from traumatic fear
Holmes, A., & Singewald, N. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.11.003 · Cited by 141 · see citing works
Behavioral and Neurobiological Mechanisms of Extinction in Pavlovian and Instrumental Learning
Todd, T. P., Vurbic, D., & Bouton, M. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.08.012 · Cited by 133 · see citing works
“above, studies of fear extinction have shown that DCS-treated animals remain vulnerable to renewal, indicating that extinction learning remains context specific (Bouton et al., 2008; Woods & Bouton, 2006).”
BackgroundSelf-citationExposure therapy in eating disorders revisited
Koskina, A., Campbell, I. C., & Schmidt, U. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.11.010 · Cited by 127 · see citing works
NMDA receptors and fear extinction: implications for cognitive behavioral therapy
Davis, M. (2011) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2011.13.4/mdavis · Cited by 118 · see citing works
Smits, J. A. J., Rosenfield, D., Otto, M. W., Marques, L., Davis, M. L., Meuret, A. E., Simon, N. M., Pollack, M. H., & Hofmann, S. G. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.06.020 · Cited by 114 · see citing works
“Consistent with the findings from animal studies (Bouton et al., 2008;Weber et al., 2007), the result of this reanalysis showed that DCS facilitated clinical improvement when patients ended their previous exposure session with low fear levels, and, conversely, inhibited clinical improvement when…”
MethodResultMyers, K. M., & Carlezon, W. A. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.01.011 · Cited by 106 · see citing works
“Systemic administration of DCS either before (Bouton et al., 2008; Ledgerwood et al., 2003, 2005; Lee et al., 2006; Mao et al., 2008; Walker et al., 2002; Weber et al., 2007; Woods and Bouton, 2006; Yang and Lu, 2005) or immediately after (Ledgerwood et al., 2003) extinction training facilitates…”
The use of cognitive enhancers in animal models of fear extinction.
Kaplan, G. B., & Moore, K. (2011) · Pharmacology, Biochemistry and Behavior · doi:10.1016/j.pbb.2011.01.009 · Cited by 104 · see citing works
A behavioural neuroscience perspective on the aetiology and treatment of anxiety disorders
Kindt, M. (2014) · Behaviour Research and Therapy · doi:10.1016/j.brat.2014.08.012 · Cited by 103 · see citing works
D-cycloserine Deters Reacquisition of Cocaine Self-Administration by Augmenting Extinction Learning
Dhonnchadha, B. Á. N., Szalay, J. J., Achat‐Mendes, C., Platt, D. M., Otto, M. W., Spealman, R. D., & Kantak, K. M. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.139 · Cited by 93 · see citing works
“However, in fear conditioning studies in rats, DCS has not been shown to facilitate within-session extinction as found in this study (Ledgerwood et al, 2003; Woods and Bouton, 2006; Bouton et al, 2008).”
Farrell, L. J., Waters, A. M., Boschen, M. J., Hattingh, L., McConnell, H. W., Oar, E. L., Collings, N., Zimmer‐Gembeck, M. J., Shelton, D., Ollendick, T. H., et al. (2013) · Depression and Anxiety · doi:10.1002/da.22132 · Cited by 92 · see citing works
“Very recent animal[44] and human[45] studies have demonstrated that positive augmentation effects are moderated by successful exposure therapy during psychotherapy sessions, that is, significant within session reduction of subjective units of distress (SUDs).”
BackgroundPsychological Mechanisms of PTSD and Its Treatment
Sripada, R. K., Rauch, S. A. M., & Liberzon, I. (2016) · Current Psychiatry Reports · doi:10.1007/s11920-016-0735-9 · Cited by 89 · see citing works
Harvey, B. H., & Shahid, M. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.06.014 · Cited by 88 · see citing works
Goode, T. D., & Maren, S. (2014) · ILAR Journal · doi:10.1093/ilar/ilu008 · Cited by 87 · see citing works
“D-Cycloserine has also shown some efficacy in reducing anxiety (Bouton et al. 2008), although its effects on extinction are mixed (Fitzgerald et al. 2013).”
BackgroundA Return to the Psychiatric Dark Ages with a Two-System Framework for Fear
Fanselow, M., & Pennington, Z. T. (2017) · Behaviour Research and Therapy · doi:10.1016/j.brat.2017.10.012 · Cited by 79 · see citing works
Grillon, C. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.04.017 · Cited by 80 · see citing works
“In rodents, DCS facilitates retention of extinction only if there is successful extinction underway during extinction training (82-84).”
Pizzimenti, C. L., & Lattal, K. M. (2015) · Genes Brain & Behavior · doi:10.1111/gbb.12187 · Cited by 78 · see citing works
“Some drugs may promote extinction, but may not weaken spontaneous recovery or contextual renewal, which may question the utility of these compounds in the clinic (e.g. Bouton et al. 2008; Stafford & Lattal 2009; Woods & Bouton 2006).”
Backgroundd-Cycloserine Augmentation of Cognitive Behavioral Therapy for Anxiety Disorders: an Update
Hofmann, S. G., Otto, M. W., Pollack, M. H., & Smits, J. A. J. (2014) · Current Psychiatry Reports · doi:10.1007/s11920-014-0532-2 · Cited by 76 · see citing works
Testing the effects of Δ9-THC and D-cycloserine on extinction of conditioned fear in humans
Klumpers, F., Denys, D., Kenemans, J. L., Grillon, C., van der Aart, J., & Baas, J. M. (2012) · Journal of Psychopharmacology · doi:10.1177/0269881111431624 · Cited by 72 · see citing works
“It has been suggested that the effects of DCS on extinction training may only be effective if extinction is well under way (Bouton et al., 2008; Weber et al., 2007).”
BackgroundEnhancement of psychosocial treatment with D-cycloserine: Models, moderators, and future directions
Otto, M. W., Kredlow, M. A., Smits, J. A. J., Hofmann, S. G., Tolin, D. F., de Kleine, R. A., van Minnen, A., Evins, A. E., & Pollack, M. H. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.09.007 · Cited by 70 · see citing works
“Consistent with this account, animal studies indicate that augmentation effects are achieved only with animals that demonstrate extinction at the time DCS is administered (49, 50).”
Cholinergic blockade frees fear extinction from its contextual dependency
Zelikowsky, M., Hast, T. A., Bennett, R. Z., Merjanian, M., Nocera, N. A., Ponnusamy, R., & Fanselow, M. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.08.006 · Cited by 71 · see citing works
“That is, extinction under DCS remains context bound and renewal is not attenuated (15, 16).”
BackgroundCognitive enhancers for anxiety disorders
Hofmann, S. G., Smits, J. A. J., Asnaani, A., Gutner, C. A., & Otto, M. W. (2010) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2010.11.020 · Cited by 68 · see citing works
From Extinction Learning to Anxiety Treatment: Mind the Gap
Carpenter, J. K., Pinaire, M., & Hofmann, S. G. (2019) · Brain Sciences · doi:10.3390/brainsci9070164 · Cited by 69 · see citing works
“Based on such results, researchers began investigating whether the NMDA agonist d-cycloserine (DCS) might enhance the effects of extinction when infused directly into the basolateral nucleus of the amygdala or administered systemically, with consistently successful results in pre-clinical animal studies [6,78,79].”
BackgroundBukalo, O., Pinard, C. R., & Holmes, A. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12779 · Cited by 67 · see citing works
“…effects of D-cycloserine are also obscured if subjects exhibit poor basal extinction (Tomilenko and Dubrovina, 2007; Weber et al., 2007; Bouton et al., 2008; Hefner et al., 2008; Whittle et al., 2013) or have a history of chronic treatment with D-cycloserine or certain antidepressant…”
BackgroundImplications of learning theory for developing programs to decrease overeating
Boutelle, K. N., & Bouton, M. E. (2015) · Appetite · doi:10.1016/j.appet.2015.05.013 · Cited by 63 · see citing works
Self-citationMaples‐Keller, J. L., Norrholm, S. D., Burton, M. S., Reiff, C. M., Coghlan, C., Jovanović, T., Yasinski, C. W., Jarboe, K. S., Rakofsky, J. J., Rauch, S. A. M., et al. (2022) · Journal of Psychopharmacology · doi:10.1177/02698811211069124 · Cited by 56 · see citing works
“The fear memory is not erased during extinction, but new learning about the likelihood of further threat develops, inhibiting previously formed fear memories (Bouton et al., 2008; Briscione et al., 2014; Myers and Davis, 2002).”
BackgroundPharmacological enhancement of fear reduction: preclinical models
Graham, B. M., Langton, J. M., & Richardson, R. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01175.x · Cited by 55 · see citing works
“…research to date has shown that while within-session extinction learning is required in order for DCS to facilitate extinction, DCS administration does not result in fear incubation in the absence of a significant reduction in fear (Weber et al., 2007; Bouton et al., 2008; Hefner et al., 2008).”
BackgroundImpaired fear extinction in adolescent rodents: Behavioural and neural analyses
Baker, K., Bisby, M. A., & Richardson, R. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.05.019 · Cited by 54 · see citing works
How stress and glucocorticoids timing-dependently affect extinction and relapse
Drexler, S. M., Merz, C. J., Jentsch, V. L., & Wolf, O. T. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.12.029 · Cited by 56 · see citing works
Effects of d ‐Cycloserine on Extinction and Reconditioning of Ethanol‐Seeking Behavior in Mice
Groblewski, P. A., Lattal, K. M., & Cunningham, C. L. (2009) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2009.00895.x · Cited by 51 · see citing works
“Specifically, Bouton et al. reported that when analyzing only the rats that showed above-median extinction levels, DCS (30 mg/kg) showed signficant facilitation of extinction (Bouton et al., 2008).”
BackgroundMethodInfluentialExtinction: Behavioral Mechanisms and Their Implications
Bouton, M. E., & Woods, A. M. (2008) · Elsevier eBooks · doi:10.1016/b978-012370509-9.00088-7 · Cited by 47 · see citing works
Self-citationRen, J., Li, X., Zhang, X., Li, M., Wang, Y., & Ma, Y. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2013.02.017 · Cited by 44 · see citing works
The informational value of contexts affects context-dependent learning
Lucke, S., Lachnit, H., Koenig, S., & Uengoer, M. (2013) · Learning & Behavior · doi:10.3758/s13420-013-0104-z · Cited by 45 · see citing works
“An additional example was provided by Bouton, Vurbic, and Woods (2008).”
MethodGraham, B. M., Callaghan, B. L., & Richardson, R. (2014) · Behaviour Research and Therapy · doi:10.1016/j.brat.2014.07.012 · Cited by 43 · see citing works
“For example, Bouton, Vurbic, and Woods (2008) re-analysed data previously reported as showing no effect of DCS on extinction retention and found the same pattern reported by Weber et al. That is, DCS enhanced extinction retention in those animals that exhibited within-session reductions in fear…”
BackgroundBernardi, R. E., & Lattal, K. M. (2010) · Behavioral Neuroscience · doi:10.1037/a0018909 · Cited by 43 · see citing works
Chai, N., Liu, J., Xue, Y.-X., Yang, C., Yan, W., Wang, H.-M., Luo, Y., Shi, H., Wang, J.-S., Bao, Y., et al. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.42 · Cited by 41 · see citing works
L-DOPA improves extinction memory retrieval after successful fear extinction
Gerlicher, A. M. V., Tüscher, O., & Kalisch, R. (2019) · Psychopharmacology · doi:10.1007/s00213-019-05301-4 · Cited by 39 · see citing works
Sartori, S. B., Maurer, V., Murphy, C. P., Schmuckermair, C., Muigg, P., Neumann, I. D., Whittle, N., & Singewald, N. (2015) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyv128 · Cited by 37 · see citing works
“, 2013) and further reinforce studies in “normally” extinguishing rodents (Weber et al., 2007; Bouton et al., 2008) as well as a recent retrospective study in patients with”
ResultHandford, C. E., Tan, S. Z. K., Lawrence, A. J., & Kim, J. H. (2014) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145714000303 · Cited by 36 · see citing works
“In another study, rats that showed belowmedian levels of extinction acquisition did not show any effects of DCS, in contrast to those showing above median extinction acquisition (Bouton et al., 2008).”
ResultDuka, T., Crombag, H. S., & Stephens, D. (2010) · Journal of Psychopharmacology · doi:10.1177/0269881110388324 · Cited by 35 · see citing works
“Contemporary learning theory (e.g. Bouton et al., 2008) suggests that extinction learning reflects new (inhibitory) learning that suppresses the expression of the original association.”
BackgroundSign-tracking behavior is difficult to extinguish and resistant to multiple cognitive enhancers
Fitzpatrick, C. J., Geary, T. N., Creeden, J. F., & Morrow, J. D. (2019) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2019.107045 · Cited by 35 · see citing works
A Contemporary Behavioral Perspective on Extinction
Vurbic, D., & Bouton, M. E. (2014) · Wiley eBooks · doi:10.1002/9781118468135.ch3 · Cited by 33 · see citing works
Self-citationD-CYCLOSERINE ENHANCES GENERALIZATION OF FEAR EXTINCTION IN CHILDREN
Byrne, S., Rapee, R. M., Richardson, R., Malhi, G. S., Jones, M., & Hudson, J. L. (2015) · Depression and Anxiety · doi:10.1002/da.22356 · Cited by 33 · see citing works
“[19] However, there is some research from both animals and humans to suggest DCS may be less effective in preventing contextual renewal of fear.[20, 21] In this study, we investigated whether DCS enhanced generalization of extinction learning for children with dog or spider phobias.”
BackgroundThe effect of ketamine on the consolidation and extinction of contextual fear memory
Clifton, N. E., Thomas, K. L., & Hall, J. (2018) · Journal of Psychopharmacology · doi:10.1177/0269881117748903 · Cited by 33 · see citing works
“Furthermore, D-cycloserine, an NMDA receptor partial agonist, facilitates the extinction of conditioned fear (Bouton et al., 2008; Gabriele and Packard, 2007; Ledgerwood et al., 2003, 2005; Norberg et al., 2008; Richardson, 2004; Walker et al., 2002).”
de Kleine, R. A., Smits, J. A. J., Hendriks, G., Becker, E. S., & van Minnen, A. (2015) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2015.06.005 · Cited by 33 · see citing works
“When the amount of extinction learning during training was experimentally restricted, DCS was found to have no augmentation (Bouton et al., 2008) or even detrimental effects (Lee, Milton, & Everitt, 2006).”
BackgroundHammond, S., Seymour, C. M., Burger, A., & Wagner, J. J. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.06.022 · Cited by 32 · see citing works
“For example, the partial NMDA receptor agonist D-cycloserine has been found to facilitate conditioned fear responses (Bouton et al., 2008; Ledgerwood et al., 2004; Walker et al., 2002).”
BackgroundMika, A., Bouchet, C. A., Bunker, P., Hellwinkel, J. E., Spence, K. G., Day, H. E. W., Campeau, S., Fleshner, M., & Greenwood, B. N. (2015) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2015.10.001 · Cited by 30 · see citing works
“Badrinarayan et al. (2012), Berlau and McGaugh (2006), Bolles (1970), Bouton, Vurbic, and Woods (2008), Chaudhury et al. (2013), Do-Monte et al. (2010), Fitzgerald, Seemann, and Maren (2014), Greenwood and Fleshner (2013), Lett, Grant, Byrne, and Koh (2000), Morris and Bouton (2007), Nicola, Taha,…”
BackgroundData-driven criteria to assess fear remission and phenotypic variability of extinction in rats
Shumake, J., Jones, C. E., Auchter, A., & Monfils, M. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2017.0035 · Cited by 30 · see citing works
d-Cycloserine facilitates extinction learning and enhances extinction-related brain activation
Klass, A., Glaubitz, B., Tegenthoff, M., & Lissek, S. (2017) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2017.08.003 · Cited by 27 · see citing works
Neuroenhancement of Exposure Therapy in Anxiety Disorders
Hofmann, S. G., Mundy, E. A., & Curtiss, J. E. (2015) · AIMS neuroscience · doi:10.3934/neuroscience.2015.3.123 · Cited by 27 · see citing works
“Unlike SSRIs, this agent itself does not produce an anxiolytic effect, but rather enhances successful extinction learning, thereby augmenting the efficacy of exposure therapy [10].”
Bolkan, S. S., & Lattal, K. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.12.009 · Cited by 31 · see citing works
Ney, L. J., Schenker, M. T., & Lipp, O. V. (2022) · Behaviour Research and Therapy · doi:10.1016/j.brat.2022.104081 · Cited by 28 · see citing works
Cognitive enhancers for the treatment of anxiety disorders
Hofmann, S. G., Fang, A., & Gutner, C. A. (2014) · Restorative Neurology and Neuroscience · doi:10.3233/rnn-139002 · Cited by 26 · see citing works
Stress following extinction learning leads to a context‐dependent return of fear
Hamacher‐Dang, T. C., Merz, C. J., & Wolf, O. T. (2014) · Psychophysiology · doi:10.1111/psyp.12384 · Cited by 26 · see citing works
Extinction: Behavioral Mechanisms and Their Implications ☆
Bouton, M. E. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809324-5.21006-7 · Cited by 25 · see citing works
Self-citationTrent, S., Abdullah, M. H., Parwana, K., Valdivieso, M. A., Hassan, Z., & Müller, C. P. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111310 · Cited by 26 · see citing works
“…et al., 1992), whereas agonists of NMDARs, such as D-cyclo-serine (DCS), delivered to the BLA prior to extinction enhance extinction learning (Bouton et al., 2008; Walker et al., 2002) and enhances consolidation of extinction when given after extinction (Langton and Richardson, 2010;…”
Groblewski, P. A., Franken, F. H., & Cunningham, C. L. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.11.018 · Cited by 25 · see citing works
“Removal of “non-learners” from analyses in order to examine the effects of extinction-specific manipulations has previously been reported (e.g. Bouton et al., 2008; Weber et al., 2007).”
BackgroundEffects of D-cycloserine on the extinction of appetitive operant learning
Vurbic, D., Gold, B., & Bouton, M. (2011) · Behavioral Neuroscience · doi:10.1037/a0024403 · Cited by 27 · see citing works
“The injection-to-extinction interval was the same as that in our fear extinction experiments (Bouton et al., 2008; Woods & Bouton, 2006).”
BackgroundMethodResultInfluentialSelf-citationStress enhances the consolidation of extinction memory in a predictive learning task
Hamacher‐Dang, T. C., Engler, H., Schedlowski, M., & Wolf, O. T. (2013) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00108 · Cited by 25 · see citing works
The effect of D-cycloserine on immediate vs. delayed extinction of learned fearPreprint
Langton, J. M., & Richardson, R. (2010) · Learning & Memory · doi:10.1101/lm.1927310 · Cited by 24 · see citing works
“Importantly, neither fear conditioning nor shock presentations prior to extinction training disrupted within-session extinction, which is an important requirement for DCS facilitation effects (e.g., Weber et al. 2007; Bouton et al. 2008).”
BackgroundTresserra, M. P., Martí‐Nicolovius, M., Guillazo‐Blanch, G., Boadas‐Vaello, P., & Vale-Martı́nez, A. (2012) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2012.11.003 · Cited by 22 · see citing works
Auchter, A., Shumake, J., Gonzalez-Lima, F., & Monfils, M. (2017) · Scientific Reports · doi:10.1038/srep46071 · Cited by 21 · see citing works
Neural circuits involved in the renewal of extinguished fear
Chen, W.-H., Wang, Y., Wang, X.-Q., & Li, H. (2017) · IUBMB Life - A Journal of the International Union of Biochemistry and Molecular Biology · doi:10.1002/iub.1636 · Cited by 20 · see citing works
“As such, D-cycloserine does not attenuate the renewal of fear to the extinguished-CS outside of extinction context (14).”
BackgroundMarchetta, E., Mancini, G. F., Morena, M., & Campolongo, P. (2022) · Current Neuropharmacology · doi:10.2174/1570159x21666221207162750 · Cited by 17 · see citing works
“These findings were additionally supported by Bouton and colleagues [72] by showing that only rats that engaged extinction learning process, that is, rats with higher extinction learning, benefited from the improving effect of DCS, whereas rats with lower indices of extinction learning did not.”
BackgroundResultAcute inhibition of mGluR5 disrupts behavioral flexibility
Sethna, F., & Wang, H. (2016) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2016.01.004 · Cited by 19 · see citing works
Posttrial d-cycloserine enhances the emotional memory of an incentive downshift event
Norris, J. N., Ortega, L. A., & Papini, M. R. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.05.001 · Cited by 18 · see citing works
“For example, in the fear conditioning situation, DCS administration either before or after training sessions has been shown to facilitate extinction [34–37], reduced reinstatement following extinction [38], and increased generalization of extinction to nonextinguished stimuli [35].”
BackgroundEbrahimi, C., Koch, S., Friedel, E., Crespo, I., Fydrich, T., Ströhle, A., Heinz, A., & Schlagenhauf, F. (2017) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2017.05.008 · Cited by 18 · see citing works
The Neurobiology of Fear Memory Reconsolidation and Psychoanalytic Theory
Gorman, J. M., & Roose, S. P. (2011) · Journal of the American Psychoanalytic Association · doi:10.1177/0003065111427724 · Cited by 17 · see citing works
Mickley, G. A., Remus, J. L., Ramos, L., Wilson, G. N., Biesan, O. R., & Ketchesin, K. D. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.08.041 · Cited by 17 · see citing works
“These data are consistent with other findings suggesting that acute DCS treatments can generally facilitate learning [43,44,58].”
ResultBaker, K., McNally, G. P., & Richardson, R. (2012) · Learning & Memory · doi:10.1101/lm.026674.112 · Cited by 17 · see citing works
“2011) but does not prevent renewal (Woods and Bouton 2006; Bouton et al. 2008).”
Memory and Posttraumatic Stress Disorder
Flor, H., & Wessa, M. (2010) · Zeitschrift für Psychologie · doi:10.1027/0044-3409/a000012 · Cited by 14 · see citing works
Sepahvand, T., Power, K. D., Qin, T., & Yuan, Q. (2023) · Biology · doi:10.3390/biology12101274 · Cited by 10 · see citing works
“NMDAR activation via systemic or intra-BLA infusion of the partial NMDAR agonist D-cycloserine facilitates threat extinction [188,189].”
d -Cycloserine reduces context specificity of sexual extinction learning
Brom, M., Laan, E. T. M., Everaerd, W. T. A. M., Spinhoven, P., Trimbos, B. J. B. M. Z., & Both, S. (2015) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2015.09.010 · Cited by 12 · see citing works
Calcineurin Participation in Hebbian and Homeostatic Plasticity Associated With Extinction
Reyes-García, S. E., & Escobar, M. L. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.685838 · Cited by 13 · see citing works
d-Cycloserine and estradiol enhance fear extinction in nulliparous but not primiparous female rats
Tang, S., & Graham, B. M. (2019) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2019.107088 · Cited by 12 · see citing works
Post-conditioning propranolol disrupts cocaine sensitization
Bernardi, R. E., & Lattal, K. M. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2012.06.015 · Cited by 10 · see citing works
“Studies have recently begun to demonstrate the need to analyze behavior in subpopulations that show differing levels of responding (Weber et al., 2007; Bouton et al., 2008; Burgos-Robles et al., 2009), including in drug conditioning paradigms (dela Cruz et al.”
Bernardi, R. E., & Lattal, K. M. (2012) · Neuroreport · doi:10.1097/wnr.0b013e32835ad246 · Cited by 10 · see citing works
Effects of d -cycloserine on individual differences in relapse of fear
King, G., Graham, B. M., & Richardson, R. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.02.005 · Cited by 9 · see citing works
“, 2004) while others have reported that it did not reduce renewal (Bouton et al., 2008; Woods and Bouton, 2006).”
Combining d-cycloserine and exposure-based CBT for the anxiety disorders.
Deveney, C. M., McHugh, R. K., Tolin, D. F., Pollack, M. H., & Otto, M. W. (2009) · Cited by 9 · see citing works
Adkins, J. M., Lynch, J., Gray, M., & Jasnow, A. (2021) · Psychopharmacology · doi:10.1007/s00213-021-05831-w · Cited by 8 · see citing works
“Furthermore, using D-cycloserine, the NMDA receptor partial agonist, enhances extinction acquisition and consolidation when given systemically or within the BLA (Bouton et al. 2008; Langton and Richardson 2008, 2010; Walker and Davis 2002) supporting an essential role for glutamate in fear extinction processes.”
MethodTanner, M. K., Hohorst, A. A., Westerman, J. D., Mendoza, C. S., Han, R., Moya, N. A., Jaime, J., Alvarez, L. M., Dryden, M. Q., Balolia, A., et al. (2024) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2024.107937 · Cited by 6 · see citing works
Otto, M. W. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.06.005 · Cited by 6 · see citing works
“It may have application to adaptation to novel situations or individuals for those with ASD and/or may have bearing on resistance to change symptoms of ASD.”
BackgroundInfluentialSepahvand, T., Nazari, N., Qin, T., Rajani, V., & Yuan, Q. (2023) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.2309986120 · Cited by 5 · see citing works
“NMDAR enhancement has been suggested as a potential therapeutic strategy to relieve maladaptive fear (61, 62), given that DCS facilitates the extinction of threat memory in animals (40, 41, 63).”
BackgroundCold Pressor “Augmentation” Does Not Differentially Improve Treatment Response for Spider Phobia
Schmidt, N. B., Richey, J. A., Funk, A. P., & Mitchell, M. A. (2010) · Cognitive Therapy and Research · doi:10.1007/s10608-010-9310-6 · Cited by 5 · see citing works
“Furthermore this approach does not require taking medication as has been done in fear extinction studies using D-cycloserine ( Bouton et al. 2008; Kalisch et al. 2009; Norberg et al. 2008).”
Result
- Authors
- Bouton, M. E., Vurbic, D., & Woods, A. M.
- Affiliations
- University of Vermont (US)
- Corresponding author
- Bouton, Mark E.
- ORCID
- Bouton, Mark E.
- Venue
- Neurobiology of Learning and Memory
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 90
- Issue
- 3
- Pages
- 504-510
- ISSN
- 1074-7427 (ISSN-L)
- PMC
- PMC2613791
- OpenAlex
- W2076008075
- Cited by
- 118
- References
- 32
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 5 · 2017: 11 · 2016: 4 · 2015: 9 · 2014: 16 · 2013: 11 · 2012: 15
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Neurobiology of Learning and Memory (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health
- 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, fear extinction, extinction learning, fear renewal
- MeSH terms
- Animals, Antimetabolites, Association Learning, Behavior, Animal, Conditioning, Classical, Cycloserine, Environment, Extinction, Psychological, Fear, Female, Rats, Wistar, Rats
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