Adolescent Anabolic Steroids, GABA and Aggression

青少年合成代谢类固醇、GABA 和攻击性

• 批准号: 6791546
• 负责人: JILL M GRIMES
• 金额: $ 2.35万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-22 至 2007-03-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6791546
• 关键词: GABA receptor; adolescence (12-20); aggression; amygdala; androgen analog; autoradiography; behavioral /social science research tag; biological models; gamma aminobutyrate; hamsters; hypothalamus; immature animal; immunocytochemistry; model design /development; neural transmission; neuropharmacology; neuroregulation; neurotransmitter antagonist; predoctoral investigator; receptor expression; steroids; substance abuse related behavior

DESCRIPTION (provided by applicant): The focus of this research proposal is to examine the role of GABA in adolescent anabolic steroid induced aggression. The GABAergic neural system is implicated in the control of aggression yet the role of GABA neurotransmission in this behavior is unclear. Exposure to AAS has been shown to increase aggression in hamsters and it is possible that exposure during adolescence alters the normal development of the GABA system. The GABAergic neural system is of particular interest in this paradigm because it has been shown that steroids directly interact with GABAA receptors in brain. Recent data shows that adolescent AAS exposure results in alterations in GAD65-ir in primary aggression areas in hamster brain and correlates with increased aggression. The goals of the experiments outlined in this proposal are 1) to manipulate adolescent AAS-induced aggression by pharmacologically targeting the GABAA receptor and 2) to examine how adolescent AAS exposure can alter the activity and/or expression of the GABA system to provide a more complete model of the circuitry involved in AAS-induced aggression. These studies will provide a better understanding of GABA's role in the neural and behavioral effects of adolescent steroid abuse.

描述（由申请人提供）： 本研究计划的重点是研究 GABA 在青少年合成代谢类固醇诱发的攻击行为中的作用。 GABA 能神经系统与攻击性的控制有关，但 GABA 神经传递在这种行为中的作用尚不清楚。暴露于 AAS 已被证明会增加仓鼠的攻击性，并且青春期期间的暴露可能会改变 GABA 系统的正常发育。 GABA 能神经系统在这一范式中特别令人感兴趣，因为已经证明类固醇直接与大脑中的 GABAA 受体相互作用。最近的数据表明，青少年 AAS 暴露会导致仓鼠大脑主要攻击区域的 GAD65-ir 发生变化，并与攻击行为增加相关。本提案中概述的实验的目标是 1) 通过药物靶向 GABAA 受体来控制青少年 AAS 诱导的攻击性，2) 检查青少年 AAS 暴露如何改变 GABA 系统的活性和/或表达，以提供更多参与 AAS 诱发攻击行为的完整电路模型。这些研究将更好地了解 GABA 在青少年类固醇滥用的神经和行为影响中的作用。