Individual differences in anxiety in females

描述(申请人提供)：本申请的目的是研究雌二醇对焦虑样行为的影响，以及雌二醇对寻找新奇行为不同的雌性大鼠边缘-下丘脑-垂体-肾上腺轴(LHPA)活动的影响。根据近交系大鼠在新环境中的活动情况，可将其分为高应答者(HR)和低应答者(LR)。HR和LR雄性大鼠在一些应激相关基因的表达模式上基本不同，并且暴露在焦虑环境中后，在情绪回路中表现出不同的糖皮质激素分泌和CFO表达模式(Kabbaj&Akil 2001；Kabbaj等人)。2000)。LHPA轴的某些分子差异是导致男性HR和LR焦虑样行为的原因。有趣的是，海马糖皮质激素受体(GR)在决定个体在“焦虑”反应中的差异方面发挥了重要作用(Kabbaj等人。2000)。我们在雌性大鼠中的初步数据显示，在它们的d1周期中，HR和LR大鼠表现出与它们的HR和LR雄鼠相似的焦虑样行为-HR没有LR那么“焦虑”。然而，在发情前期，雌鼠的焦虑行为趋于一致，表现为在焦虑测试中表现出与HR大鼠相似的行为。在这项应用中，我们计划验证雌激素与HR和LR大鼠焦虑均衡化有关的假设。我们还将扩展对HR和LR女性的行为观察，并描述她们在暴露于两种焦虑行为测试：开阔视野和社会互动测试后的基础LHPA轴活动和神经元激活。我们还将探讨海马区GR在决定HR和LR雌性大鼠“焦虑”水平中的作用。在整个研究过程中，雌鼠将与雄鼠进行比较。目的1：雌二醇在决定焦虑反应个体差异中的作用：不同组去卵巢的雌性HR和LR大鼠在一次注射雌二醇(0，2，5和10ug)后24小时，观察其焦虑样行为和LHPA轴活动。在所有的行为和分子指标上，女性将与男性进行比较。目的2：海马区GR在确定雌性焦虑样行为个体差异中的作用：我们将研究GR拮抗剂(RU 38486)在海马区注入对去卵巢和去卵巢的雌性大鼠焦虑样行为的影响。以雄性大鼠为阳性对照。

DESCRIPTION (provided by applicant): The purpose of this application is to examine the effects of estradiol on anxiety like behaviors and the effects of estradiol on Limbic-Hypothalamo-Pituitary-Adrenal axis (LHPA) activity in female rats that differ in their novelty seeking behavior. Based on their locomotor activity in a novel environment outbred rats are categorized as High responders (HR) or Low Responders (LR). HR and LR male rats differ basally in the patterns of expression of some stress related genes, and exhibit different patterns of glucocorticoid secretion and cFos expression in the emotional circuitry following exposure to an anxiogenic environment (Kabbaj & Akil 2001; Kabbaj et al. 2000). Some molecular differences in LHPA axis were responsible for males' HR and LR anxiety like behavior. Of interest, hippocampal glucocorticoid receptors (GR) play a major role in determining individual differences in "anxiety" responses (Kabbaj et al. 2000). Our preliminary data in females show that HR and LR rats, in their D1 cycle, exhibit similar anxiety like behavior as their HR and LR male counterpart-HR less "anxious" than LR. However, during proestrus there is an equalization of anxiety like behaviors of HR and LR females, in that LR rats behave like HR rats in the anxiety test. In this application we plan to verify the hypothesis that estradiol is implicated in this equalization of anxiety in HR and LR rats. We will also extend the behavioral observations in HR and LR females and describe their basal LHPA axis activity as well as neuronal activation following exposure to two behavioral tests of anxiety: the open field and the social interaction test. We will also explore the role of hippocampal GR in determining "anxiety" levels of HR and LR female rats. Throughout the studies female rats will be compared to their males' counterpart. Aim 1: Role of estradiol in determining individual differences in anxiety-responses: Different groups of ovariectomized female HR and LR rats will be examined for their anxiety like behaviors and LHPA axis activity 24h after one injection of estradiol (0, 2, 5 or 10 ug). Females will be compared to their male counterpart for all the behavioral and molecular measures. Aim 2: Role of hippocampal GR in determining individual differences in anxiety like behaviors in females: We will examine the effect of a GR antagonist (RU 38486) infused in the hippocampus on anxiety like behaviors of HR and LR ovariectomized females. Male rats will be used as positive controls.