Peptidergic mediation of the stress response: relationship between aversive and appetitive brain circuits

应激反应的肽能介导：厌恶和食欲脑回路之间的关系

• 批准号: RGPIN-2015-05388
• 负责人: Merali, Zul
• 金额: $ 2.4万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=684912
• 关键词: Peptidergic; mediation; stress; response; relationship

The long-term objective of this research program is to better understand how the brain interprets various types of stressors or salient stimuli (including appetitive events) and coordinates internal bodily responses as well as behavioral outputs in response to these events. This is based on the observation that exposure to threatening (or aversive) stimuli or to appetitive (or rewarding) stimuli can activate some of the same neural circuits. In this project, we will explore the behavioral, neurochemical and neuroanatomical substrates underlying responses to 1) `classic stressors' including naturalistic psychogenic (psychological) stressors (exposure to a larger `bully' leading to social defeat), neurogenic stressors (physical restraint), which have psychological and physical attributes and pure physiological stressors (e.g. exposure to immune-type stressors) and 2) appetitive stimuli (sexual behavior, palatable snack). We have deliberately selected to study these types of naturalistic stressors, as they are ethologically sound and more likely to yield heuristically and practically useful information. Moreover, the selection of the appetitive stimuli was based on data showing comparable activation of the hypothalamic-pituitary adrenal axis to social defeat and restraint making these stressors of opposite valence well suited for comparative studies. The brain utilizes various chemical signals (neurotransmitters) to communicate not only with the rest of the body but also between different regions of the brain itself. One particular class of such transmitter molecules that seem important in responding to stress are small hormone-like molecules called peptides. We are able to monitor the release of various brain transmitters/peptides, in freely behaving animals - without them being 'aware' of this process. We will also monitor the release of various hormones and assess levels of motivation and emotional responses in these animals as stressor exposure is known to affect these behavioral processes. It is hoped that this work will shed new light on the stressor-specific neurochemical mechanisms that link perception of stress to its translation into the classical stress response. Moreover, we hope to uncover the links between stress and reward systems, which may have bearing on adaptive responses to stressors, and potentially uncover how stressful events come to influence motivational behavior and cognitive appraisal.**

这项研究计划的长期目标是更好地了解大脑如何解释各种类型的压力源或显著刺激（包括食欲事件），并协调内部身体反应以及对这些事件的行为输出。这是基于这样的观察：暴露于威胁性（或厌恶性）刺激或食欲性（或奖励性）刺激可以激活某些相同的神经回路。在这个项目中，我们将探讨行为，神经化学和神经解剖学的基础上的反应1）“经典的压力”，包括自然主义的心因性（心理）压力源（暴露于更大的“欺负者”导致社交失败），神经源性压力源（物理约束），具有心理和身体属性以及纯粹的生理压力源（例如暴露于免疫型应激源）和2）食欲刺激（性行为、可口的零食）。我们特意选择研究这些类型的自然主义压力源，因为它们在行为学上是合理的，更有可能产生理论上和实际上有用的信息。此外，食欲刺激的选择是基于数据显示下丘脑-垂体-肾上腺轴的激活与社会失败和约束的可比性，使得这些相反效价的应激源非常适合进行比较研究。大脑利用各种化学信号（神经递质）不仅与身体的其他部分进行交流，而且还在大脑本身的不同区域之间进行交流。在对压力做出反应的过程中，一类特殊的递质分子似乎很重要，它们是一种叫做肽的小分子，类似于蜜蜂。我们能够监测各种大脑递质/肽的释放，在自由行为的动物-没有他们被'意识到'这一过程。我们还将监测各种激素的释放，并评估这些动物的动机和情绪反应水平，因为已知压力暴露会影响这些行为过程。希望这项工作将揭示新的压力特异性神经化学机制，连接到经典的压力反应的翻译感受到的压力。此外，我们希望揭示压力和奖励系统之间的联系，这可能与对压力源的适应性反应有关，并可能揭示压力事件如何影响动机行为和认知评价。