ReviewEffects of D-Cycloserine on Extinction: Translation From Preclinical to Clinical Work
Section snippets
The Role of N-Methyl-D-Aspartate Receptors in Extinction
Extinction typically does not result from an erasure of the original fear memory but instead represents a new form of learning that acts to inhibit or suppress the original fear memory (Bouton and Bolles 1979a, Konorski 1967, Pavlov 1927). A large body of literature suggests that glutamate acting at the N-methyl-D-aspartate (NMDA) receptor is critically involved in learning and memory (Bear 1996, Castellano et al 2001, Morris et al 1990, Newcomer and Krystal 2001). For example, Miserendino et
Facilitation of Extinction With an NMDA Partial Agonist
Because the blockade of the NMDA receptor impairs extinction, it was logical to wonder if enhancing the functioning of that receptor would enhance extinction. To test this we administered a compound called D-cycloserine (DCS) either systemically or directly into the rats’ amygdala before extinction training and then tested retention of extinction the next day (Walker et al 2002). D-cycloserine does not bind to the NMDA receptor itself but to another receptor on the NMDA protein called the
Does DCS Cause “Generalized” Extinction?
Perhaps the most surprising result from the recent preclinical studies on DCS and extinction is that DCS seems to lead to generalized extinction (Ledgerwood et al 2005). In that study, rats were initially trained with two different cues (i.e., a light and a tone), each paired with a loud aversive noise. The next day some rats were given two sessions (separated by 2 hours) of extinction training with the visual cue (six non-reinforced exposures to the 2-min light in each session). Immediately
DCS Reduces Reinstatement of Learned Fear After Extinction
In another study, Ledgerwood et al (2004) found that DCS might block relapse (i.e., a return of the learned fear response) that normally occurs when extinction training is followed by a stress, a phenomenon referred to as reinstatement. In that study, rats were first trained to be afraid of a light by pairing it with a footshock and then, the next day, given extinction training followed by injection of either DCS or saline. To equate levels of fear before stress, the saline-treated rats were
DCS Does Not Seem to Facilitate Fear Conditioning and Might Even Reduce It
If DCS is so effective in facilitating learning, then one might wonder whether it could actually be harmful if combined with exposure-based psychotherapy. For example, bringing to mind awful memories of a traumatic event can lead to sensitization rather than extinction if a full therapeutic exposure is not carried out (Bisson et al 1997, Mayou et al 2000). Perhaps sensitization would be exacerbated by DCS by reinstantiating the fearful memories. Thus far none of us have seen any evidence of
A Clinical Test of Combining DCS With Behavioral Exposure Therapy for Acrophobia
Recently we tested whether DCS given in combination with exposure therapy for the treatment of specific phobia in humans would improve the effectiveness of this therapy (Ressler et al 2004). We wished to examine the ability of DCS to enhance exposure therapy in humans with the most optimally controlled form of psychotherapeutic learning available. Virtual reality exposure (VRE) therapy is ideal for clinical research assessment because exposure and testing is identical between patients, is well
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