The Effect of Gonadal Steriods on Pavlovian Fear Conditioning

性腺类固醇对巴甫洛夫恐惧调节的影响

• 批准号: 7197127
• 负责人: DONNA J TOUFEXIS
• 金额: $ 21.33万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7197127
• 关键词: Acoustics; Address; Affect; Agonist; Androgen Receptor; Androstenediol; Androstenediols; Animals; Anxiety; Anxiety Disorders; Applications Grants; Behavioral; Brain; Cognition; Cues; Data; Development; Discrimination; Discrimination Learning; Disease; Elements; Emotional; Emotions; Estrogen Receptors; Estrogens; Etiology; Exploratory/Developmental Grant; Female; Fright; Gender; Gonadal Hormones; Gonadal Steroid Hormones; Hippocampal Formation; Hippocampus (Brain); Hormones; Human; Individual; Investigation; Laboratories; Learning; Measures; Membrane; Memory; Mental Depression; Metabolism; Methodology; Methods; Modeling; Panic Disorder; Pathology; Pharmaceutical Preparations; Physiological; Play; Post-Traumatic Stress Disorders; Process; Protocols documentation; Public Health; Purpose; Rattus; Reporting; Role; Selective Estrogen Receptor Modulators; Sex Characteristics; Stanolone; Steroids; System; Testosterone; Thinking; Time; Training; Woman; base; conditioned fear; conditioning; hormone regulation; male; men; receptor; response; sex; showing emotion; steroid hormone

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.

描述（由申请人提供）：焦虑和恐惧失调障碍非常普遍。众所周知，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，但无论男女，激素调节恐惧回路的潜在机制仍然未知。针对 PA-03-169，此探索性/发展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腺激素对雄性和雌性动物的恐惧的影响。在这里，我们将采用新的适应版本的辨别训练范例 AX+.BX-，并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，来测量特定性腺类固醇受体激活的效果影响恐惧的激活和抑制。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取、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：在性腺切除的雄性和雌性大鼠中，性腺类固醇对恐惧获得的影响，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，这些研究将有助于阐明各种性腺类固醇对恐惧学习的贡献。每个个体的性别。这些调查的结果不仅会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方面的性别差异。