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中，还是发生在啮齿动物的实验模型中，都是通过在没有任何负面后果(即消退或暴露疗法)的情况下将受到恐惧的有机体暴露在可怕的刺激中来减少的。然而，当恐惧的刺激在与暴露环境不同的环境中遇到时，恐惧往往会重新出现。在老鼠身上，我们发现，在动物灭绝期间，通过服用抗胆碱能药物来干扰动物处理上下文的能力，可以防止恐惧的重新出现。这项提议将决定这种药物的有益效果是否转化为社交焦虑患者的暴露疗法。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反复接受公开演讲。参与者将在每次暴露治疗前随机接受安慰剂、0.2 mg/.01毫升东方碱、0.3毫克/.01毫升东方碱或0.4毫克/.01毫升东芝碱滴鼻给药。暴露治疗完成一个月后，将通过比较暴露治疗期间使用的相同虚拟背景下与暴露治疗期间使用的不同背景下的公众演讲的生理和主观反应来测试背景更新。其目标是确定与最大程度减少上下文更新相关的东莨菪碱剂量。此外，二次分析将试图确定哪些人最受益于暴露疗法的东莨菪碱增强。

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.