Molecular mechanism of D-cycloserine action

Project: Research projectExploratory/Developmental Grants

Description

DESCRIPTION (provided by applicant): In the US alone, an estimated 40 million adults suffer from anxiety disorders which may have debilitating consequences. Common forms of anxiety disorders include social anxiety, specific phobias and post-traumatic stress disorders (PTSD). Current therapy for anxiety disorders have unpleasant side effects and may fail. Thus, there is an urgent need to develop new therapeutic interventions. The treatment of choice for a number of anxiety disorders is exposure-based psychotherapy. Pilot studies in human show that D-cycloserine (DCS), an agonist for N-methyl-D-aspartate (NMDA) receptors, augments the effects of exposure therapy for simple and social phobia, obsessive compulsive disorder (OCD) and panic disorder. Despite very promising translational results demonstrating a robust effect of DCS in enhancing exposure therapy, the molecular mechanism of DCS action is unknown. In this proposal using behavioral, electrophysiological and biochemical techniques we will assess the effect of DCS on synaptic strengthening or depotentiation of cortico-amygdala circuits. The long- term goal of this proposal is to understand NMDA receptor mediated mechanisms of learning in the amygdala. PUBLIC HEALTH RELEVANCE: The treatment of choice for a number of anxiety disorders is exposure-based psychotherapy. D-cycloserine (DCS) augments the effects of exposure therapy for simple and social phobia, obsessive compulsive disorder (OCD) and panic disorder. This study will assess the molecular pathway of DCS action.
StatusFinished
Effective start/end date7/1/104/30/13

Funding

  • National Institutes of Health: $216,750.00
  • National Institutes of Health: $178,819.00

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Cycloserine
Implosive Therapy
Anxiety Disorders
Panic Disorder
Obsessive-Compulsive Disorder
Amygdala
N-Methyl-D-Aspartate Receptors
Psychotherapy
Long-Term Synaptic Depression
Post-Traumatic Stress Disorders
Learning
Social Phobia
Therapeutics
Specific Phobia