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.
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.
|Gupta, Subhash C; Hillman, Brandon G; Prakash, Anand et al. (2013) Effect of D-cycloserine in conjunction with fear extinction training on extracellular signal-regulated kinase activation in the medial prefrontal cortex and amygdala in rat. Eur J Neurosci 37:1811-22|
|Hillman, Brandon G; Gupta, Subhash C; Stairs, Dustin J et al. (2011) Behavioral analysis of NR2C knockout mouse reveals deficit in acquisition of conditioned fear and working memory. Neurobiol Learn Mem 95:404-14|