Original Article
Neuropsychopharmacology (2008) 33, 3096–3102; doi:10.1038/npp.2008.32; published online 19 March 2008
D-Cycloserine Facilitates Extinction the First Time but not the Second Time: An Examination of the Role of NMDA Across the Course of Repeated Extinction Sessions
Julia M Langton1 and Rick Richardson1
1School of Psychology, The University of New South Wales, Sydney, NSW, Australia
Correspondence: JM Langton, School of Psychology, The University of New South Wales, Sydney, NSW 2052, Australia. Tel: +61 2 93853025; Fax: +61 2 93853641; E-mail: jlangton@psy.unsw.edu.au
Received 28 November 2007; Revised 5 February 2008; Accepted 8 February 2008; Published online 19 March 2008.
Abstract
Extinction of learned fear is facilitated by the partial NMDA agonist D-cycloserine (DCS). However, some studies suggest that the involvement of NMDA in learning differs depending on whether learning is for the first or second time. The current study aimed to extend these findings by examining the role of NMDA in extinction for the first and the second time. Specifically, the present series of experiments used Pavlovian fear conditioning and extinction paradigms to compare the effect of DCS on extinction of fear to a light CS the first and second time around. As found previously, DCS facilitated extinction of learned fear (Experiment 1). A novel finding, however, was that DCS did not facilitate the re-extinction of fear to this same CS following retraining (Experiments 2A and 2B). Finally, it was demonstrated that the transition from NMDA-dependent to NMDA-independent extinction was stimulus specific (Experiment 3). That is, rats were first trained to fear a CS (light); this fear was then extinguished. Following this, rats were then retrained to fear the same CS (light) or a new CS (white noise). When given a second extinction session, DCS was found to facilitate extinction of the new CS but not the original CS. The results of this series of experiments suggest that the role of NMDA in extinction depends on whether extinction is new learning (first extinction) or retrieval of a previous extinction memory (re-extinction).
Keywords:
D-cycloserine, NMDA, extinction, re-extinction, fear, relapse
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
REVIEWS
Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic
Nature Neuroscience Review (01 Sep 2007)
NEWS AND VIEWS
Behavioural neuroscience The circuit of fear
Nature News and Views (31 Jul 2008)
Neurobiology A new image for fear and emotion
Nature News and Views (04 Jun 1998)
RESEARCH
Heredity Original Article
Neuropsychopharmacology Original Article

