Novel paradigm attenuates traumatic memories and prevents return of fear

新颖的范例可以减轻创伤记忆并防止恐惧再次出现

• 批准号: 7789363
• 负责人: Marie H. Monfils
• 金额: $ 21.94万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7789363
• 关键词: Amygdaloid structure; Attenuated; Behavioral; Behavioral Paradigm; Biochemical Markers; Brain region; Chemosensitization; Clinical; Clinical Treatment; Conditioned Stimulus; Electrophysiology (science); Emotional; Extinction (Psychology); Fright; Functional Magnetic Resonance Imaging; Hour; Human; Individual; Laboratories; Lateral; Learning; Memory; Mental disorders; Modification; Outcome; Pharmaceutical Preparations; Phase; Phosphorylation; Post-Traumatic Stress Disorders; Process; Protocols documentation; Public Health; Rattus; Relapse; Research; Retrieval; Sampling; Sensory; Shock; Specific Phobia; Stimulus; Synapses; Techniques; Testing; Time; Training; Update; Variant; Work; attenuation; base; blood oxygenation level dependent response; classical conditioning; clinical efficacy; conditioned fear; follow-up; improved; in vivo; neural circuit; neuromechanism; novel; prevent; public health relevance; relating to nervous system; research study; response

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.

描述（由申请人提供）：夸张或持续的恐惧是精神疾病中的常见。尽管通过研究帕夫洛维亚调节的研究，在发现恐惧学习的神经基础上取得了很多进展，但对于如何减少或消除病理性病例中的创伤性记忆知之甚少，这是极大的临床关注。当最初中性刺激（条件刺激，CS；例如，语气）获得引起恐惧反应的能力时，可以形成联想的情绪记忆。在实验室环境中使用了两个范式（重新溶解和灭绝的封锁），以减少获得的恐惧（Nader等，2000；参考，年）；但是，这些技术的临床功效受到限制：重新溶解阻塞需要潜在有毒药物，而灭绝通常不是永久性的。我的初步发现表明，我们设计了一种新颖的行为范式，可减弱和防止恐惧记忆的回归。我们的结果表明，对常用的临床治疗（暴露疗法）的细微修改可以大大改善预后，并减少患有创伤后应激障碍或特定恐惧症患者复发的潜力。在拟议的研究中，我建议研究这种持续衰减恐惧的神经机制，以消除我们的新型范式如何与标准灭绝机制区分开来。我们将在大鼠和人类研究中并行进行这些实验，然后测试这种形式的治疗是否可用于治疗患有特定恐惧症的个体。 公共卫生相关性：夸张或持续的恐惧是精神疾病的普遍情况。在实验室环境中使用了两个范式（重新溶解和灭绝的封锁），以减少获得的恐惧；但是，这些技术的临床功效受到限制。在这里，我们提出了一种新颖的行为范式，可减弱和防止恐惧记忆的回归。我们的发现表明，对常用的临床治疗（暴露疗法）的细微修改可以大大改善预后，并减少患有创伤后应激障碍或特定恐惧症患者复发的潜力。