A Rodent Model of Behavioral Inhibition

描述（由申请人提供）： 儿童和成人的“行为抑制”或“害羞”与几种负面的健康后果有关。大约20%的儿童确实受到行为抑制，即他们从新的或不熟悉的环境中退缩，并表现出更大的压力和恐惧相关生理系统的激活，包括下丘脑-垂体-肾上腺（HPA）轴。拟议的研究将测试在常用的实验室大鼠（褐家鼠）中被确定为新恐惧症的行为特征是否类似于在人类中被确定为行为抑制的特征，因此大鼠可以提供一种动物模型，用于对这种特征的原因和后果进行实验研究。通过开发一个非人类的行为抑制模型，可以进行寿命发育和实验研究，以确定该特征的环境和遗传起源，并确定潜在的补救干预措施，如果发现该特征主要对健康不利。 本研究将使用Sprague-Dawley大鼠进行，Sprague-Dawley大鼠是一种大鼠品系，其中个体探索新环境的意愿存在自然发生的差异，并且肾上腺皮质释放的应激激素（糖皮质激素）与该性状相关。该研究将通过测量个体大鼠在不同条件下和不同时间的行为反应来评估这种行为特征的稳定性，并将测量糖皮质激素产生的动态，以确定受抑制的个体是否经历更长，更慢性的糖皮质激素升高，从而使他们更容易出现健康问题。最后，鉴于早期同伴社会互动对人格形成的重要性，研究将使用实验研究来确定青春期社会互动如何影响新恐惧症的发展。这项研究将为未来研究行为抑制/害羞的发展和长期后果提供基础。

DESCRIPTION (provided by applicant): 'Behavioral inhibition' or 'shyness' among children and adults has been associated with several negative health consequences. Approximately 20% of children are reliably behaviorally inhibited - i.e. they withdraw from novel or unfamiliar circumstances and show greater activation of stress- and fear-associated physiological systems including the hypothalamic-pituitary-adrenal (HPA) axis. The proposed research will test whether a behavioral trait identified as neophobia in the commonly used laboratory rat (Rattus norvegicus) is analogous to the trait identified as behavioral inhibition in humans, such that rats could provide an animal model in which to conduct experimental studies on the causes and consequences of this trait. By developing a non-human model of behavioral inhibition, it becomes possible to conduct life span developmental and experimental studies to determine the environmental and genetic origins of the trait, and to determine potential remedial interventions if the trait is found to be primarily disadvantageous to health. This research will be conducted with Sprague-Dawley rats, a strain of rat in which naturally-occurring variance exists in individual willingness to explore a novel environment and for which stress hormones (glucocorticoids) released by adrenal cortex are related to this trait. The research will assess the stability of this behavioral trait by measuring individual rats' behavioral responses across different conditions and across time, and will measure the dynamics of glucocorticoid production to determine if inhibited individuals experience longer, more chronic, elevations in glucocorticoids, thus making them more prone to health problems. Finally, given the importance of early peer social interactions on personality formation, the research will use an experimental study to determine how peri-pubertal social interactions affect the development of neophobia. This research will provide the basis for future research on the development and long-term consequences of behavioral inhibition / shyness.