d-Cycloserine facilitates context-specific fear extinction learning

Bouton, Mark E.; Vurbic, Drina; Woods, Amanda M.

doi:10.1016/j.nlm.2008.07.003

Cited by 110 publications

(104 citation statements)

References 27 publications

(41 reference statements)

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“…Several studies have investigated ways to enhance fear extinction (Abraham et al, 2012;Berlau and McGaugh, 2006;McGaugh et al, 1990;Mueller et al, 2008). Treatment with D-cycloserine, a partial agonist of NMDA receptors at the glycine modulatory site, enhanced extinction memory (Bouton et al, 2008;Mao et al, 2008;Walker et al, 2002). NE infusion into the infralimbic cortex improved extinction (Mueller et al, 2008), and this is consistent with the present results in which NE infusion into the CA1 immediately after extinction enhanced extinction consolidation.…”

Section: Role Of Hippocampal Ne In the Persistence Of Extinction Ltmsupporting

confidence: 90%

Delayed Noradrenergic Activation in the Dorsal Hippocampus Promotes the Long-Term Persistence of Extinguished Fear

Chai

Liu

Xue

et al. 2014

Neuropsychopharmacol

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Fear extinction has been extensively studied, but little is known about the molecular processes that underlie the persistence of extinction long-term memory (LTM). We found that microinfusion of norepinephrine (NE) into the CA1 area of the dorsal hippocampus during the early phase (0 h) after extinction enhanced extinction LTM at 2 and 14 days after extinction. Intra-CA1 infusion of NE during the late phase (12 h) after extinction selectively promoted extinction LTM at 14 days after extinction that was blocked by the b-receptor antagonist propranolol, protein kinase A (PKA) inhibitor Rp-cAMPS, and protein synthesis inhibitors anisomycin and emetine. The phosphorylation levels of PKA, cyclic adenosine monophosphate response element-binding protein (CREB), GluR1, and the membrane GluR1 level were increased by NE during the late phase after extinction that was also blocked by propranolol and Rp-cAMPS. These results suggest that the enhancement of extinction LTM persistence induced by NE requires the activation of the b-receptor/PKA/CREB signaling pathway and membrane GluR1 trafficking. Moreover, extinction increased the phosphorylation levels of Erk1/2, CREB, and GluR1, and the membrane GluR1 level during the late phase, and anisomycin/emetine alone disrupted the persistence of extinction LTM, indicating that the persistence of extinction LTM requires late-phase protein synthesis in the CA1. Propranolol and Rp-cAMPS did not completely disrupt the persistence of extinction LTM, suggesting that another b-receptor/PKA-independent mechanism underlies the persistence of extinction LTM. Altogether, our results showed that enhancing hippocampal noradrenergic activity during the late phase after extinction selectively promotes the persistence of extinction LTM.

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Section: Role Of Hippocampal Ne In the Persistence Of Extinction Ltmsupporting

confidence: 90%

Delayed Noradrenergic Activation in the Dorsal Hippocampus Promotes the Long-Term Persistence of Extinguished Fear

Chai

Liu

Xue

et al. 2014

Neuropsychopharmacol

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“…Later studies showed that d-cycloserine is mainly involved in the consolidation of newly formed extinction memories, because post-extinction administration of the drug produced the same effect (up to four hours). Others have shown the d-cycloserine prevents reinstatement, although it does not influence renewal and rapid reacquisition in rodents (Bouton, Vurbic, & Woods, 2008;Ledgerwood, Richardson, & Cranney, 2004;) and other experimental data show that d-cycloserine may augment fear under some conditions in both rodent and human samples (Vervliet, 2008). Nevertheless, in excellent clinical translation work, dcycloserine has been shown to result in less fear at follow-up, after exposure therapy for specific human fears (Ressler et al 2004).…”

Section: Enhancing Inhibitory Regulationmentioning

confidence: 99%

Role of Inhibition in Exposure Therapy

Craske

Liao

Brown

et al. 2012

Journal of Experimental Psychopathology

195

140

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While many researchers have largely focused on principles of systematic desensitization and habituation in explaining fear extinction, these processes have mixed evidence at best. In particular, these models do not account for spontaneous recovery or reinstatement of fear, nor do they explain the context dependency of extinction or rapid reacquisition. This may in part account for the significant number of patients who fail to respond to our available treatments which rely on these principles in designing exposure sessions. However, recent research is converging to suggest that an inhibitory model of fear reduction, in which the original feared association (CS-US) remains but is inhibited by a newly formed association (CS-noUS) representing safety, holds promise in explaining the long-term attenuation of fear and anxiety. This paper reviews research in a number of areas, including neuroimaging, psychophysiology, and psychopharmacology that all provide support for the inhibition model of anxiety. Limitations to this body of research are discussed, along with recommendations for future research and suggestions for improving exposure therapy for fear and anxiety disorders. Clinical implications discussed in this paper include incorporating random and variable practice in exposure sessions, multiple contexts, and pharmacological aides, among others.

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“…However, in a final renewal test, response recovery was similar in strength across the two conditions. An additional example was provided by Bouton, Vurbic, and Woods (2008). The authors reported that the administration of D-Cycloserine facilitated extinction learning as compared to a saline control condition, but renewal was equivalent in both conditions.…”

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confidence: 99%

The informational value of contexts affects context-dependent learning

et al. 2013

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In two predictive-learning experiments, we investigated the role of the informational value of contexts for the formation of context-dependent behavior. During Phase 1 of each experiment, participants received either a conditional discrimination in which contexts were relevant (Group Relevant) or a simple discrimination in which contexts were irrelevant (Group Irrelevant). Each experiment also included an ABA renewal procedure. Participants received Z+ in context A during Phase 1, extinction of Z in context B during Phase 2, and were tested with Z in context A during a test phase. In each experiment, extinction of Z proceeded faster and was followed by stronger response recovery in Group Relevant than in Group Irrelevant. In Experiment 2, which included recording of eye-gaze behavior, dwell times on contexts were longer in Group Relevant than in Group Irrelevant. Our results support the idea that relevant contexts receive more attention, leading to stronger context specificity of learning.

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d-Cycloserine facilitates context-specific fear extinction learning

Cited by 110 publications

References 27 publications

Delayed Noradrenergic Activation in the Dorsal Hippocampus Promotes the Long-Term Persistence of Extinguished Fear

Delayed Noradrenergic Activation in the Dorsal Hippocampus Promotes the Long-Term Persistence of Extinguished Fear

Role of Inhibition in Exposure Therapy

The informational value of contexts affects context-dependent learning

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