Facilitation of Conditioned Fear Extinction by Systemic Administration or Intra-Amygdala Infusions of d-Cycloserine as Assessed with Fear-Potentiated Startle in Rats

By D. Walker, K. Ressler, K. Lu, Michael Davis. Journal of Neuroscience, 2002

818 citations recorded by the source corpus.

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 μg/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.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Developmental Neuroscience

View Paper: https://www.semanticscholar.org/paper/7917a5167ad4a980360d3088b4f4fe5d45a795b4

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Citations in the corpus

Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear. (2004, background): “Uponbreakingtheblind,wefoundnodifferencebe-tweensubjectsreportingadverseeffectswithplaceboandthosereportingadverseeffectswithDCS.”
Behavioral and neural analysis of extinction. (2002, methodology): “In a extinction memory. study that was similarly designed to that of Falls et al. Despite this substantial body of evidence for the (1992), we (Walker et al., 2002) found that DCS facilitated involvement of NMDA receptors in fear extinction, there extinction in a dose-dependent manner following…”
Context, ambiguity, and unlearning: sources of relapse after behavioral extinction. (2002, background): “Interestingly, facilitation of NMDA receptor function might also facilitate extinction (Walker et al 2002).”
Extinction learning in humans: role of the amygdala and vmPFC. (2004, background): “In addition, an intraamygdala injection of an NMDA agonist, D-cycloser- Results ine, enhanced extinction learning (Walker et al., 2002).”
Prefrontal mechanisms in extinction of conditioned fear. (2006, positive): “DCS has been shown to be effective when infused into the LA (Walker et al 2002), and clinical studies show that adminisering DCS to acrophobic subjects who are undergoing exposure herapy improves the effectiveness of the therapy (Ressler et al 004).”
Plastic Synaptic Networks of the Amygdala for the Acquisition, Expression, and Extinction of Conditioned Fear (2010, neutral): “Furthermore, the NMDA receptor agonist D-cycloserine, a partial agonist acting at the glycine-recognition site of the NMDA receptor, facilitates extinction of fear-potentiated startle or conditioned freezing when administered shortly before or after extinction training (237, 238, 512, 530).”
Towards a theory of chronic pain (2008, neutral): “DCycloserine (DCS) given systemically or centrally enhances cognitive processes (Stromme and Myhrer, 2002), improves attention and memory (Hughes, 2004; Vertes, 2006), and facilitates fear extinction (Richardson et al., 2004; Walker et al., 2002) through de novo memory trace formation involving n-me”
The amygdala modulates the consolidation of memories of emotionally arousing experiences. (2004, background): “Additionally, Walker et al. (2002) reported that intra-amygdala drug infusions (D-cycloserine) administered before extinction training enhance the extinction of conditioned fear.”
Fear extinction in rats: implications for human brain imaging and anxiety disorders. (2006, background): “Paralleling this, microinjection of an NMDA agonist into the amygdala facilitated fear extinction (Walker et al., 2002; Ledgerwood et al., 2003).”
Working Memory: Theories, Models, and Controversies (2015, neutral): “Systemic drugs that facilitate extinction (without altering fear expression) include growth factor FGF-2 (Graham & Richardson 2011), adrenergic antagonist yohimbine (Morris & Bouton 2007), NMDA agonist d-cycloserine (Walker et al. 2002), cannabinoids (Lafenetre et al.”
The value of spontaneous alternation behavior (SAB) as a test of retention in pharmacological investigations of memory. (2004, background): “For example, although glucose and the partial agonist of NMDA receptors, D-cycloserine, improve memory [82,83], they can also be anxiolytic [84,85] thereby potentially increasing SAB which is known to be antagonised by fear [32].”
Contributions of the amygdala to emotion processing: from animal models to human behavior. (2005, background): “They have shown that blockade of NMDA receptors in the amygdala disrupts extinction and that facilitation of NMDA receptor function with d-cycloserine enhances extinction (Walker and Davis, 2002; Walker et al., 2002).”
Fear Extinction as a Model for Translational Neuroscience: Ten Years of Progress (2012, background): “Systemic drugs that facilitate extinction (without altering fear expression) include growth factor FGF-2 (Graham & Richardson 2011), adrenergic antagonist yohimbine (Morris & Bouton 2007), NMDA agonist d-cycloserine (Walker et al. 2002), cannabinoids (Lafenetre et al.”