The Effect of Gonadal Steriods on Pavlovian Fear Conditioning

描述（由申请人提供）：焦虑和恐惧失调非常普遍。众所周知，这些疾病对女性的影响大约是对男性的两倍，这种差异被认为与激素调节有关，但激素调节男女恐惧回路的潜在机制尚不清楚。作为对PA-03-169的回应，本探索性/发展性拨款提案的目的是开发一种信息更丰富、更准确的方法来确定性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改编版的歧视训练范式AX+。BX-，以及高度特异性雌激素受体激动剂和雄激素受体特异性睾酮代谢物的使用，来测量特定性腺类固醇受体的激活对恐惧的激活和抑制的影响。本项目的具体目标是：1。验证AX+， BX-歧视学习范式作为研究恐惧习得、表达和抑制的激素调节模型的有效性。2. 在去性腺的雄性和雌性大鼠中，利用该模型研究了性腺激素对恐惧习得的影响，以及性腺激素对恐惧表达的影响。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，这些研究将有助于阐明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说明了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.