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

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。这是基于这样一种观察，即暴露在威胁性(或厌恶)刺激或欲望(或奖励)刺激下可以激活一些相同的神经回路。在这个项目中，我们将探索对1)经典应激源的行为、神经化学和神经解剖学基础，包括自然主义心理(心理)应激源(暴露于较大的导致社会失败的‘欺凌’)、具有心理和生理属性的神经源性应激源(身体约束)和纯生理应激源(例如，暴露于免疫型应激源)和2)食欲刺激(性行为、美味的零食)。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健全的，更有可能提供启发式和实用的有用信息。此外，食欲刺激的选择是基于数据显示，与社会挫败和约束相比，下丘脑-垂体肾上腺轴的激活使这些相反价位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，而且还在大脑的不同区域之间进行交流。在压力反应中，有一类特殊的递质分子似乎很重要，那就是被称为多肽的类似激素的小分子。我们能够监测自由行为的动物体内各种大脑递质/多肽的释放--而它们并没有意识到这一过程。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，因为已知应激源暴露会影响这些行为过程。人们希望这项工作将为应激源特定的神经化学机制提供新的线索，这些机制将应激感知与其转化为经典的应激反应联系在一起。此外，我们希望揭示压力和奖励系统之间的联系，这可能会影响对压力源的适应性反应，并可能揭示压力事件是如何影响动机行为和认知评估的。

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.**