ADOLESCENT ANABOLIC STEROIDS, VASOPRESSION, & AGGRESSION

青少年合成代谢类固醇、血管加压、

• 批准号: 6492709
• 负责人: Richard H. Melloni
• 金额: $ 0.94万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2002-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6492709
• 关键词: adolescence (12-20); aggression; androgen analog; arginine vasopressin; autoradiography; behavioral /social science research tag; blood tests; complementary DNA; developmental psychology; disease /disorder model; drug abuse; drug administration rate /duration; hamsters; hormone receptor; immunoelectron microscopy; in situ hybridization; neuropharmacology; psychopharmacology; receptor binding; receptor expression; substance abuse related behavior; testosterone; western blottings

DESCRIPTION: (Applicant's Abstract) The abuse of androgenic-anabolic steroids (AAS) has increased dramatically amongst the adolescent population and represents a serious drug problem in the United States. The most consistently cited behavioral sequelae of AAS abuse is increased aggressive behavior. The arginine vasopressin (AVP) neural system has been strongly implicated in the regulation of aggressive behavior. It is hypothesized that abuse of anabolic steroids during the adolescent period of neural development results in increased aggressive behavior correlated with developmental changes in the AVP neural system. These changes may be a function of alterations in the expression of AVP and/or the expression and activity of specific AVP receptors. Alternatively, these developmental changes may be due to modifications in the synaptic connectivity of the AVP neural system. Studies outlined in this proposal will utilize an animal model to examine the behavioral and neurobiological effects of high dose AAS exposure during a period that is physiologically similar to adolescence in humans. The first set of experiments will determine whether exposure to AAS during adolescent development facilitates aggressive behavior in golden hamsters using the resident/intruder paradigm of offensive aggression. The next set of experiments will determine whether AAS exposure during adolescence alters the molecular biology and neurochemistry of the AVP neural system. These studies will employ the use of cDNA fragments, antibodies, and selective receptor ligands to visualize and quantitate the activity of the genes encoding AVP and the AVP V1A subtype receptor. The last set of experiments will determine whether exposure to AAS during adolescent development alters the synaptic connections of the AVP neural system. Changes in synaptic connectivity will be visualized and quantitated by wide-field digital microscopy and immunoelectron microscopy. The data obtained from these studies should provide valuable information regarding the increased risk of aggressive and violent behavior in those individuals who abuse AAS during early life, and the neurobiological sequelae of prolonged high dose use of AAS. This knowledge is important in helping us to identify developmental periods that are particularly vulnerable to environmental insult, and to document the neurobiological changes that may predispose individuals to behave in a self-destructive or violent manner later in life.

描述：（申请人的摘要） 滥用雄激素代谢类固醇（AAS）显着增加了 在青少年人口中，代表了严重的毒品问题 美国。 AAS的最一致的行为后遗症 滥用是增加侵略性行为。 精氨酸加压素（AVP） 神经系统与侵略性的调节密切相关 行为。 假设滥用合成代谢类固醇 神经发育的青少年时期导致侵略性增加 行为与AVP神经系统的发展变化相关。 这些变化可能是AVP表达变化的函数 和/或特定AVP受体的表达和活性。 或者，这些发展变化可能是由于修改 AVP神经系统的突触连通性。 概述的研究 该建议将利用动物模型来检查行为和 高剂量AAS暴露在一个时期的神经生物学作用 生理上与人类青春期相似。 第一组 实验将确定青少年期间是否暴露于AAS 发展促进了使用金仓鼠的侵略性行为 进攻性侵略的居民/入侵者范式。 下一组 实验将确定青春期中的AAS暴露是否改变 AVP神经系统的分子生物学和神经化学。 这些 研究将采用cDNA片段，抗体和选择性的使用 受体配体可视化和定量基因活性 编码AVP和AVP V1A亚型受体。 最后一组实验 将确定在青少年发展期间接触AAS是否改变 AVP神经系统的突触连接。 突触的变化 连通性将通过广阔的数字可视化和定量 显微镜和免疫电子显微镜。 从这些研究中获得的数据应提供有价值的信息 关于那些侵略性和暴力行为的风险增加 在早期虐待AA的个人和神经生物学 长时间高剂量使用AAS的后遗症。 这些知识很重要 帮助我们确定特别是 容易受到环境侮辱的影响，并记录神经生物学 可能使个人在自我毁灭或 以后生活中的暴力方式。