D-Cycloserine Administered Directly to Infralimbic Medial Prefrontal Cortex Enhances Extinction Memory in Sucrose-Seeking Animals

J. Peters, T.J. de Vries

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31 Citations (Scopus)


d-Cycloserine (DCS), a co-agonist at the N-methyl-D-aspartate (NMDA) receptor, has proven to be an effective adjunct to cognitive behavioral therapies that utilize extinction. This pharmacological-based enhancement of extinction memory has been primarily demonstrated in neuropsychiatric disorders characterized by pathological fear (e.g. posttraumatic stress disorder and various phobias). More recently, there has been an interest in applying such a strategy in the disorders of appetitive learning (e.g. substance abuse and other addictions), but these studies have generated mixed results. Here we first examined whether extinction memory encoding in a sucrose self-administration model is dependent on NMDA receptors. The NMDA antagonist (±)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (5. mg/kg, i.p.) administered 2. h prior to the first extinction training session effectively inhibited extinction memory recall 24. h later, without affecting the expression of the conditioned sucrose-seeking response while the drug was on board. This profile of effects suggests a specific effect on extinction memory consolidation. Next, we sought to enhance extinction memory using the co-agonist DCS (10. μg/side) by infusion directly into infralimbic medial prefrontal cortex, a brain site implicated in extinction memory recall in conditioned fear models. Indeed, infusion of DCS immediately after the first extinction training session effectively enhanced extinction memory recall 24. h later. Collectively, these data suggest that the neurobiological mechanisms and the neurocircuitry mediating extinction memory are similar regardless of the valence (aversive or appetitive) of the conditioned behavior, and that similar pharmacological strategies for treatment may be applied to neuropsychiatric disorders characterized by a failure to inhibit pathological emotional memories. © 2012 IBRO.
Original languageEnglish
Pages (from-to)24-30
Publication statusPublished - 2013

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