The Effect of Gonadal Steriods on Pavlovian Fear Conditioning

描述（由申请人提供）：焦虑和恐惧失调症非常普遍。据了解，这些疾病对女性的影响大约是男性的两倍，这种差异被认为与激素调节有关，但在任何性别中，恐惧回路的激素调节的潜在机制仍然未知。本探索/发展补助金提案的目的是响应PA-03-169，旨在开发一种信息量更大、更准确的方法，以确定性腺激素对雄性和雌性动物恐惧的影响。在这里，我们将采用一个新的适应版本的歧视训练范例AX+.BX-，沿着使用高度特异性的雌激素受体激动剂和雄激素受体特异性睾酮代谢物，以测量特定的性腺类固醇受体的激活对激活和抑制恐惧的影响。该项目的具体目标是：1。验证AX+，BX-辨别学习范式作为检查恐惧获得、表达和抑制的激素调节的模型的使用。2.使用该模型来检查：性腺类固醇对性腺切除的雄性和雌性大鼠的恐惧获得的影响，以及性腺类固醇对恐惧表达的影响。这些研究的数据将开始阐明这些类固醇激素对情绪记忆形成和表达的特定方面的具体影响，此外，这些研究将有助于澄清各种性腺类固醇对每个性别的恐惧学习的贡献。这些调查的结果不仅可以说明每个性别的情绪学习的发展和表达，而且还将开始解决创伤后应激障碍、抑郁症和焦虑症以及恐慌症发生率的性别差异。

DESCRIPTION (provided by applicant): Disorders of anxiety and fear dysregulation are highly prevalent. It is known that these disorders affect women approximately two times more than they affect men, and this disparity is thought to be related to hormone regulation, yet the underlying mechanism of hormone regulation of the fear circuit in either sex remains unknown. The purpose of this Exploratory/ Developmental Grant proposal, in response to PA-03-169, is to develop a more informative and accurate method to determine the effect that gonadal hormones have on fear in both male and female animals. Here, we will employ a new adapted version of the discrimination training paradigm AX+.BX-, along with the use of highly specific estrogen receptor agonists and an androgen receptor-specific testosterone metabolite, to measure the effect that activation of specific gonadal steroid receptors have on both the activation and inhibition of fear. The specific aims of this project are: 1. to validate the use of the AX+, BX- discrimination learning paradigm as a model for examining hormone modulation of fear acquisition, expression and inhibition. 2. to use this model to examine: the effect of gonadal steroids on fear acquisition, and the effect of gonadal steroids on fear expression, in gonadectomized male and female rats. Data from these studies will begin to elucidate the specific effects that these steroid hormones have on very particular aspects of emotional memory formation and expression in general, and moreover, these studies will help to clarify the contribution that the various gonadal steroids make to fear learning in each individual sex . Results from these investigations would not only speak to the development, and expression of emotional learning within each individual sex, but will also begin to address the gender disparity in the occurrence of PTSD, depression and anxiety illness, and panic disorder.