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Molecular mechanism of D-cycloserine action

D-环丝氨酸作用的分子机制

基本信息

批准号：
7990363
负责人：
Shashank Manohar Dravid
金额：
$ 21.68万
依托单位：
CREIGHTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7990363
关键词：
Address Adult Adverse effects Agonist Amygdaloid structure Animals Anxiety Anxiety Disorders Bathing Behavioral Biochemical Cell Nucleus Cells Clinical Cognitive Therapy Complement Cycloserine Development Effectiveness Extinction (Psychology)Fright Glutamates Goals Homosynaptic Depression Human Immunohistochemistry Intercalated Cell Knowledge Lateral Lead Learning Measures Medial Mediating Mediator of activation protein Memory Molecular Molecular Mechanisms of Action N-Methyl-D-Aspartate Receptors N-Methylaspartate Neurons Obsessive-Compulsive Disorder Panic Disorder Pathway interactions Patients Pharmaceutical Preparations Pilot Projects Play Post-Traumatic Stress Disorders Prefrontal Cortex Protocols documentation Psychotherapy Rattus Rodent Model Role Signal Transduction Site Slice Social Phobia Specific Phobia Synapses Synaptic plasticity Techniques Testing Therapeutic Training Walkers Work base conditioned fear design insight neural circuit neuronal excitability novel therapeutic intervention public health relevance social stress related disorder therapeutic target

项目摘要

DESCRIPTION (provided by applicant): In the US alone, an estimated 40 million adults suffer from anxiety disorders which may have debilitating consequences. Common forms of anxiety disorders include social anxiety, specific phobias and post-traumatic stress disorders (PTSD). Current therapy for anxiety disorders have unpleasant side effects and may fail. Thus, there is an urgent need to develop new therapeutic interventions. The treatment of choice for a number of anxiety disorders is exposure-based psychotherapy. Pilot studies in human show that D-cycloserine (DCS), an agonist for N-methyl-D-aspartate (NMDA) receptors, augments the effects of exposure therapy for simple and social phobia, obsessive compulsive disorder (OCD) and panic disorder. Despite very promising translational results demonstrating a robust effect of DCS in enhancing exposure therapy, the molecular mechanism of DCS action is unknown. In this proposal using behavioral, electrophysiological and biochemical techniques we will assess the effect of DCS on synaptic strengthening or depotentiation of cortico-amygdala circuits. The long- term goal of this proposal is to understand NMDA receptor mediated mechanisms of learning in the amygdala. PUBLIC HEALTH RELEVANCE: The treatment of choice for a number of anxiety disorders is exposure-based psychotherapy. D-cycloserine (DCS) augments the effects of exposure therapy for simple and social phobia, obsessive compulsive disorder (OCD) and panic disorder. This study will assess the molecular pathway of DCS action.

描述（由申请人提供）：仅在美国，估计有4000万成年人患有焦虑症，这可能会导致衰弱的后果。焦虑症的常见形式包括社交焦虑、特定恐惧症和创伤后应激障碍（PTSD）。目前对焦虑症的治疗有令人不快的副作用，而且可能会失败。因此，迫切需要开发新的治疗干预措施。许多焦虑症的治疗选择是基于暴露的心理疗法。人体初步研究表明，n -甲基- d -天冬氨酸（NMDA）受体的激动剂d -环丝氨酸（DCS）可以增强暴露疗法对单纯和社交恐惧症、强迫症（OCD）和恐慌症的疗效。尽管非常有希望的转化结果表明DCS在增强暴露治疗方面具有强大的作用，但DCS作用的分子机制尚不清楚。在这个建议中，我们将使用行为学、电生理和生化技术来评估DCS对皮质-杏仁核回路突触增强或减弱的影响。本研究的长期目标是了解杏仁核中NMDA受体介导的学习机制。