Novel paradigm attenuates traumatic memories and prevents return of fear

描述（由申请人提供）：夸大或持续的恐惧是精神疾病的常见现象。尽管通过巴甫洛夫条件反射的研究，在揭示恐惧学习的神经基础方面取得了很大进展，但如何在病理病例中减少或消除创伤记忆却知之甚少，这是临床非常关注的问题。当最初的中性刺激（条件刺激，CS，如音调）与非条件刺激（US，如电击）配对后获得引发恐惧反应的能力时，可以形成联想情绪记忆。两种范式（再巩固封锁和消退）已在实验室环境中用于减少获得性恐惧（Nader等人，2000；参考文献，年）；然而，这些技术的临床疗效有限：再巩固阻断需要潜在毒性药物，而消除通常不是永久性的。我的初步发现表明，我们已经设计了一种新的行为模式，可以减弱并防止恐惧记忆的回归。我们的研究结果表明，对一种常用的临床治疗方法（暴露疗法）进行细微的修改可以极大地改善结果，并减少创伤后应激障碍或特定恐惧症患者复发的可能性。在拟议的研究中，我建议检查这种持续减弱恐惧的神经机制，以消除我们的新范式与标准消退机制的区别。我们将在大鼠和人类研究中同时进行这些实验，然后测试这种形式的治疗是否可以用于治疗患有特定恐惧症的个体。

DESCRIPTION (provided by applicant): Exaggerated or persistent fear is a common occurrence in psychiatric disorders. Although much progress has been made in uncovering the neural basis of fear learning through studies of Pavlovian conditioning, little is known about how to reduce or eliminate traumatic memories in pathological cases, which is of great clinical concern. Associative emotional memories can be formed when an initially neutral stimulus (conditioned stimulus, CS; e.g., a tone) acquires the ability to elicit fear responses after being paired with an unconditioned stimulus (US; e.g., a shock). Two paradigms (blockade of reconsolidation and extinction) have been used in the laboratory setting to reduce acquired fear (Nader et al., 2000; REF, YEAR); however, the clinical efficacy of these techniques has been limited: reconsolidation blockade requires potentially toxic drugs, while extinction is not typically permanent. My preliminary findings indicated that we have devised a novel behavioral paradigm that attenuates and prevents the return of fear memories. Our results indicate that subtle modifications to a commonly employed clinical treatment (exposure therapy) could greatly improve outcome, and reduce the potential for relapse in individuals suffering from post-traumatic stress disorder or specific phobias. In the proposed studies, I propose to examine the neural mechanisms that underlie this persistent attenuation of fear, in order to disambiguate how our novel paradigm distinguishes itself from standard extinction mechanisms. We will perform these experiments in rat and human studies in parallel, and then test whether this form of therapy can be used to treat individuals that suffer from specific phobias. PUBLIC HEALTH RELEVANCE: Exaggerated or persistent fear is a common occurrence in psychiatric disorders. Two paradigms (blockade of reconsolidation and extinction) have been used in the laboratory setting to reduce acquired fear; however, the clinical efficacy of these techniques has been limited. Here, we present a novel behavioral paradigm that attenuates and prevents the return of fear memories. Our findings indicate that subtle modifications to a commonly employed clinical treatment (exposure therapy) could greatly improve outcome, and reduce the potential for relapse in individuals suffering from post-traumatic stress disorder or specific phobias.