Individual differences in anxiety in females

描述（由申请人提供）：本申请的目的是检查雌二醇对焦虑样行为的影响，以及雌二醇对新奇行为不同的雌性大鼠的边缘-下丘脑-垂体-肾上腺轴（LHPA）活性的影响。基于它们在新环境中的运动活动，远交大鼠被分类为高反应者（HR）或低反应者（LR）。HR和LR雄性大鼠在一些应激相关基因的表达模式方面存在基本差异，并且在暴露于致焦虑环境后，在情感回路中表现出不同的糖皮质激素分泌和cFos表达模式（Kabbaj &阿基勒2001; Kabbaj et al. 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。令人感兴趣的是，海马糖皮质激素受体（GR）在确定“焦虑”反应的个体差异中起主要作用（Kabbaj et al. 2000）。我们的初步数据显示，在雌性HR和LR大鼠，在他们的D1周期，表现出类似的焦虑行为，因为他们的HR和LR男性对应-HR少“焦虑”比LR。然而，在发情前期，HR和LR雌性的焦虑样行为是均衡的，因为LR大鼠在焦虑试验中表现得像HR大鼠。在本申请中，我们计划验证这一假设，雌二醇是牵连在这种平衡的焦虑在HR和LR大鼠。我们还将扩展HR和LR女性的行为观察，并描述其基础LHPA轴活动以及暴露于两种焦虑行为测试后的神经元激活：旷场和社交互动测试。我们还将探讨海马GR在确定HR和LR雌性大鼠的“焦虑”水平中的作用。在整个研究过程中，将雌性大鼠与雄性大鼠进行比较。目标1：雌二醇在确定焦虑反应的个体差异中的作用：在一次注射雌二醇（0、2、5或10 μ g）后24小时，检查不同组的卵巢切除雌性HR和LR大鼠的焦虑样行为和LHPA轴活性。雌性动物将与雄性动物进行所有行为和分子测量。目标二：海马GR在确定女性焦虑样行为的个体差异中的作用：我们将检查海马中输注的GR拮抗剂（RU 38486）对HR和LR卵巢切除女性的焦虑样行为的影响。雄性大鼠将用作阳性对照。

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.