Cholinergic Decontextualization of Exposure Therapy for Anxiety

描述（由申请人提供）：恐惧，无论是发生在患有焦虑症的人类身上，还是发生在啮齿类动物的实验模型中，通过将受惊吓的生物体暴露于恐惧刺激而没有任何负面后果（即灭绝或暴露疗法）来减少恐惧。然而，当恐惧刺激在不同于暴露环境的环境中遇到时，恐惧往往会更新。在老鼠身上，我们发现通过使用抗胆碱能药物来干扰动物在灭绝期间处理环境的能力，可以防止恐惧的重新产生。该提案将确定这种药物的有益效果是否转化为社交焦虑人群的暴露疗法。为此，100名害怕公开演讲的社交恐惧症患者将在虚拟现实环境中接受反复的公开演讲体验。在每次暴露治疗之前，参与者将被随机分配到药物安慰剂，0.2 mg/.01 mL东莨菪碱，0.3 mg/.01 mL东莨菪碱或0.4 mg/.01 mL东莨菪碱，通过滴鼻给药。暴露疗法完成一个月后，情境更新将通过比较在暴露疗法中使用的相同虚拟情境中与在暴露疗法中使用的不同情境中对公开演讲的生理和主观反应来进行测试。目的是确定东莨菪碱的剂量与环境更新的最大减少有关。此外，一项二次分析将试图确定那些从东莨菪碱增强暴露疗法中获益最多的个体。

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.