Anabolic Androgenic Steroid Effects on Brain and Behavior

合成代谢雄激素类固醇对大脑和行为的影响

基本信息

批准号：
7664333
负责人：
Marilyn Y MCGINNIS
金额：
$ 20.84万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-02-20 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7664333
关键词：
Adolescence Adolescent Adult Adverse effects Affect Aggressive behavior Amygdaloid structure Anabolic steroids Androgen Receptor Androgens Animal Model Animal Testing Animals Behavioral Biological Assay Brain Brain Stem Cells Child Child Abuse Childhood Chronic Complement Corpus striatum structure Data Dendrites Dendritic Spines Development Dorsal Dose Exhibits Exposure to Fluorescent Dyes Fluoxetine Goals Gonadal Hormones Health High Pressure Liquid Chromatography Hippocampus (Brain)Hormonal Hormonal Change Human Hypothalamic structure Impulsive Behavior Impulsivity Individual Investigation Lead Learning Link Long-Term Effects Measurement Measures Medial Mediating Modeling Nature Nervous system structure Neurons Neurosecretory Systems Occupations Pattern Perception Pharmaceutical Preparations Predictive Factor Prevalence Problem behavior Puberty Rattus Receptor Inhibition Reporting Research Response Latencies Risk Role Selective Serotonin Reuptake Inhibitor Serotonin Site Stimulus Tail Teenagers Testing Testosterone Training Tryptophan Vertebral column Violence Work brain behavior density early childhood experience follow-up frontal lobe hydroxyflutamide immunoreactivity indexing male neurochemistry prepuberty prevent reproductive research study response social

项目摘要

DESCRIPTION (provided by applicant): The prevalence of anabolic androgenic steroid (AAS) use has risen in teenagers and is now a major health problem. AAS use during adolescence is particularly alarming because puberty is a hormonally sensitive period during which adult behavioral patterns develop, and one consistent effect of AAS use is increased aggression. The goal of this research is to determine the factors underlying aggressive and impulsive behaviors in adolescent AAS users, employing rats as the animal model. The proposed studies will continue our work on AAS-exposed pubertal males. Aim I will identify early experiential factors that predict whether aggression will be potentiated in AAS-treated males. The effects of early exposure to low serotonin and to social subjugation will be investigated. The effects of exposure to social subjugation on serotonin will be assessed. Aim II will investigate the role of impulsivity in AAS-induced aggression. The first aim will employ a test battery we have developed for measuring impulsivity in a sociosexual encounter. An advantage of this test is that it is biologically relevant and does not require extensive training or teaming. In the second experiment, the role of AAS in mediating impulsivity will be determined using the androgen receptor antagonist, hydroxyflutamide. In the third experiment, the role of serotonin in mediating impulsivity will be tested in AAS and gonadally intact rats using the SSRI, fluoxetine. Aim III will investigate the long term effects of pubertal AAS exposure. The first experiment will identify long term effects of pubertal exposure to low brain serotonin in AAS-exposed males. The second experiment will determine whether increased aggressive behavior in socially subjugated males persists into adulthood. In Aim IV we will assess the neuroanatomical effects of pubertal AAS exposure. Since gonadal hormones influence dendritic spine density, we will determine whether spine density is affected by AAS exposure during puberty. Spine densities in the medial amygdala and dorsal hippocampus will be quantified using the fluorescent dye, Dil. Disruption of the endogenous hormonal milieu during puberty may lead to irreversible behavioral and neurochemical consequences, and have a long-term negative impact on adult behavioral patterns. By superimposing AAS exposure on the developing nervous system, these studies will answer important questions regarding the effects of AAS use on the maturation of adolescent brain and aggressive behavior.

描述（由申请人提供）：青少年中合成代谢雄激素类固醇 (AAS) 的使用率有所上升，现已成为一个主要的健康问题。青春期期间使用 AAS 特别令人担忧，因为青春期是一个荷尔蒙敏感期，在此期间成人行为模式的发展，并且使用 AAS 的一个一致影响是攻击性增加。本研究的目标是使用大鼠作为动物模型，确定青少年 AAS 用户攻击性和冲动行为的潜在因素。拟议的研究将继续我们对暴露于 AAS 的青春期男性的研究。我的目标是确定早期的经验因素，这些因素可以预测经 AAS 治疗的男性的攻击性是否会增强。将调查早期接触低血清素和社会压迫的影响。将评估暴露于社会压迫对血清素的影响。目标 II 将研究冲动在 AAS 引发的攻击行为中的作用。第一个目标是使用我们开发的测试电池来测量社交性接触中的冲动。该测试的一个优点是它具有生物学相关性，并且不需要大量的培训或团队合作。在第二个实验中，将使用雄激素受体拮抗剂羟基氟他胺来确定 AAS 在调节冲动中的作用。在第三个实验中，将使用 SSRI（氟西汀）在 AAS 和性腺完整的大鼠中测试血清素在调节冲动中的作用。目标 III 将研究青春期 AAS 暴露的长期影响。第一个实验将确定暴露于 AAS 的男性青春期暴露于低脑血清素的长期影响。第二个实验将确定社会屈服的男性攻击性行为的增加是否会持续到成年期。在目标 IV 中，我们将评估青春期 AAS 暴露对神经解剖学的影响。由于性腺激素影响树突棘密度，我们将确定树突棘密度是否受到青春期 AAS 暴露的影响。内侧杏仁核和背侧海马的脊柱密度将使用荧光染料 Dil 进行量化。青春期内源性激素环境的破坏可能会导致不可逆转的行为和神经化学后果，并对成人的行为模式产生长期的负面影响。通过将 AAS 暴露叠加在发育中的神经系统上，这些研究将回答有关 AAS 使用对青少年大脑成熟和攻击行为的影响的重要问题。