Cholinergic Decontextualization of Exposure Therapy for Anxiety

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DESCRIPTION (provided by applicant): Fear, whether it occurs in humans suffering from an anxiety disorder or in experimental models with rodents, is reduced by exposing the frightened organism to the fearful stimulus in the absence of any negative consequences (i.e., extinction, or exposure therapy). However, fear often renews when the feared stimulus is encountered in a context different from the exposure context. In rats, we found that interfering with the animal's ability to process contexts during extinction by administering an anticholinergic drug prevented fear renewal. This proposal will determine if the beneficial effect of this drug translates to exposure therapy in socially anxious humans. To this end, 100 individuals with Social Phobia who fear public speaking will undergo repeated sessions of exposure to public speaking, within a virtual reality context. Participants will be randomized to either drug placebo, .2mg/.01 mL Scopolamine, .3mg/.01 mL Scopolamine or .4mg/.01 mL Scopolamine, administered via nasal drops, prior to each session of exposure therapy. One month after completion of exposure therapy, context renewal will be tested by comparing physiological and subjective responses to public speaking in the same virtual context as used during exposure therapy versus a context different than the one used during exposure therapy. The goal is to identify the dose of Scopolamine associated with the greatest reduction in context renewal. In addition, a secondary analysis will attempt to identify those individuals who benefit most from Scopolamine-augmentation of exposure therapy.