The role of the androgen receptor in behavior

雄激素受体在行为中的作用

• 批准号: 7230772
• 负责人: Damian Gabriel Zuloaga
• 金额: $ 3.25万
• 依托单位: MICHIGAN STATE 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 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7230772
• 关键词: androgen receptor; animal developmental psychology; anxiety; anxiety disorders; behavior test; behavioral /social science research tag; developmental genetics; developmental neurobiology; gender difference; gene mutation; hormone regulation /control mechanism; hormone sensitivity /resistance; laboratory mouse; laboratory rat; male castration; neural information processing; open field behavior; ovariectomy; predoctoral investigator; psychopharmacology; sensory feedback; sex development disorder; startle reaction; testicular feminization; testosterone

DESCRIPTION (provided by applicant): Hormone receptors in the brain, particularly the estrogen receptor, have been shown to play a major role in the development and maintenance of sex differences in behavior. However, the role of the androgen receptor in this process is less understood. Therefore I propose to investigate the role of the androgen receptor in two types of behavior, sensorimotor gating and anxiety, using male mice and rats with the testicular feminization mutation (TFM), a mutation in the androgen receptor gene that renders the protein nonfunctional. Experiment 1 will test the hypothesis that the androgen receptor is involved in the regulation of sensorimotor gating and anxiety-related behaviors in adulthood by comparing behavior between TFM males, wild type males and wild type females. Since TFM male mice and rats have different circulating testosterone (T) levels than their wild type siblings, in Experiment 2 all animals will be gonadectomized, administered T, and tested for the same behaviors to reveal whether circulating T is acting on AR in adulthood to affect behavior. Experiment 3 will test whether differences in sensorimotor gating and anxiety in adulthood are the result of androgen induced organization during development.

描述（由申请人提供）：大脑中的激素受体，特别是雌激素受体，已被证明在行为性别差异的发展和维持中发挥着重要作用。然而，人们对雄激素受体在此过程中的作用知之甚少。因此，我建议使用带有睾丸女性化突变（TFM）的雄性小鼠和大鼠来研究雄激素受体在感觉运动门控和焦虑这两种行为中的作用，TFM是雄激素受体基因中的一种突变，导致蛋白质失去功能。实验1将通过比较TFM雄性、野生型雄性和野生型雌性之间的行为来检验雄激素受体参与成年期感觉运动门控和焦虑相关行为的调节这一假设。由于 TFM 雄性小鼠和大鼠的循环睾酮 (T) 水平与其野生型同胞不同，因此在实验 2 中，所有动物都将被切除性腺，注射 T，并测试相同的行为，以揭示循环 T 是否在成年后作用于 AR影响行为。实验3将测试成年期感觉运动门控和焦虑的差异是否是发育过程中雄激素诱导组织的结果。