Adolescent Anabolic Steroids, GABA and Aggression

描述（由申请人提供）： 本研究的重点是探讨GABA在青少年合成代谢类固醇引起的攻击中的作用。GABA能神经系统与攻击性控制有关，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，青春期的暴露可能会改变GABA系统的正常发育。GABA能神经系统在该范例中特别令人感兴趣，因为已经显示类固醇直接与脑中的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GAD 65-ir的改变，并与攻击性增加相关。本实验的目的是：1）通过靶向GABAA受体的抑制来控制青少年AAS诱导的攻击行为; 2）研究青少年AAS暴露如何改变GABA系统的活性和/或表达，以提供一个更完整的AAS诱导攻击行为的电路模型。这些研究将提供一个更好地了解GABA的作用，在青少年类固醇滥用的神经和行为的影响。

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.