Effects of repeated stress on amygdala function during adolescence

青春期反复应激对杏仁核功能的影响

• 批准号: 9223732
• 负责人: Jeremy E Rosenkranz
• 金额: $ 27.3万
• 依托单位: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-16 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9223732
• 关键词: Adolescence; Adolescent; Adult; Adverse effects; Affective; Affective Symptoms; Age; Amygdaloid structure; Anhedonia; Antidepressive Agents; Anxiety; Appetitive Behavior; Behavior; Behavioral; Chronic stress; Conflict (Psychology); Dependency; Depressive disorder; Desire for food; Development; Electrophysiology (science); Equilibrium; Functional disorder; Goals; Hyperactive behavior; In Vitro; Lead; Mental Depression; Mood Disorders; Neurobiology; Neurons; Nucleus Accumbens; Output; Pathway interactions; Pharmaceutical Preparations; Pharmacology; Phenotype; Physiology; Population; Prevalence; Public Health; Rattus; Research; Stimulus; Stress; Structure of terminal stria nuclei of preoptic region; Syndrome; Testing; Weight; adolescent patient; age related; child depression; clinical efficacy; depressive behavior; depressive symptoms; experimental study; gamma-Aminobutyric Acid; hedonic; in vivo; innovation; insight; neurobiological mechanism; novel; phenomenological models; psychiatric symptom; public health relevance; relating to nervous system; response

 DESCRIPTION (provided by applicant): Depression phenomenology is different in adolescents, and many antidepressants do not work in adolescents. But the reasons for this are not known. One possible explanation is differences in the pathophysiology of depression. The long-term goal of our research is to determine how abnormalities of the amygdala contribute to symptoms of affective disorders. The short-term goal of these experiments is to test whether differences in specific amygdala output pathways underlie differences between adolescent and adult affective behavior. The basolateral amygdala (BLA) guides anxiety behavior and many appetitive behaviors via outputs to different neural regions. A balance between these BLA outputs balances anxiety and appetitive behavior. This project will test the hypothesis that the balance between major BLA output pathways is different in adolescents, and this leads to a shift towards appetitive behaviors. Repeated stress mimics several symptoms of depression, including anhedonia and anxiety. This project will also test the hypothesis that repeated stress shifts the balance of major BLA outputs towards those involved with anxiety and away from those that guide hedonic behaviors, but via different mechanisms in adults and adolescents. The Aims of this project are to determine the balance between two major BLA output paths in adolescents, to determine if repeated stress exerts opposite actions on two major BLA output paths, and to determine if targeting BLA paths selectively reverses behavioral effects of stress. This study will compare the age- dependent mechanisms for the effects of repeated stress. This project is significant because it can demonstrate a novel neurobiological mechanism for differences in the balance of anxiety and hedonic behaviors across age, and novel targetable mechanisms for the impact of stress on emergence of psychiatric symptoms in adolescents. These experiments are innovative because they will test amygdala function in the context of its place in behaviorally important circuits. This approach will yield exciting new information about subsets of BLA circuits. This project will lead to novel insight about how a deficit in the BLA can lead to abnormalities that comprise a psychiatric syndrome, and is expected to uncover a new avenue in the development of an alternative pharmacological approach to treat depression in adolescents.

 描述（由申请人提供）：抑郁症的现象在青少年中是不同的，许多抗抑郁药对青少年不起作用，但其中的一个可能的解释是抑郁症的病理生理学差异。研究的目的是确定杏仁核的异常如何导致情感障碍的症状。这些实验的短期目标是测试特定杏仁核输出途径的差异是否是青少年和成人之间差异的基础。基底外侧杏仁核（BLA）通过向不同神经区域的输出来引导焦虑行为和许多食欲行为。该项目将测试主要 BLA 输出通路之间的平衡的假设。青少年的情况有所不同，这会导致食欲行为的转变，类似于抑郁症的几种症状，包括快感缺失和焦虑。该项目还将检验重复的压力会改变平衡的假设。 BLA 的主要输出针对那些涉及焦虑的人，而不是那些指导享乐行为的人，但通过成人和青少年的不同机制。该项目的目的是确定青少年中两个主要 BLA 输出路径之间的平衡，以确定是否重复压力。对两条主要的 BLA 输出路径施加相反的作用，并确定针对 BLA 路径是否选择性地逆转压力的行为影响。这项研究将比较重复压力影响的年龄依赖性机制。该项目意义重大，因为它可以证明一种新颖的方法。神经生物学机制不同年龄阶段焦虑和享乐行为平衡的差异，以及压力对青少年精神症状出现影响的新的目标机制。这些实验具有创新性，因为它们将在行为重要回路中测试杏仁核的功能。这种方法将产生有关 BLA 电路子集的令人兴奋的新信息。该项目将带来关于 BLA 缺陷如何产生的新见解。 导致包括精神综合症在内的异常，并有望为开发治疗青少年抑郁症的替代药理学方法开辟新途径。