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

• 批准号: 7331843
• 负责人: Marilyn Y MCGINNIS
• 金额: $ 14.15万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-20 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7331843
• 关键词: aggression; androgen analog; androgen receptor; animal puberty; antidepressants; behavioral /social science research tag; biological models; drug adverse effect; drug interactions; estrogen receptors; estrogens; fertility; fluoxetine; high performance liquid chromatography; laboratory rat; male; psychopharmacology; receptor binding; reproductive development; serotonin; sex behavior; substance abuse related behavior; substance abuse related disorder; testosterone

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）：合成代谢雄激素类固醇（AAS）的流行率在青少年中增加了，现在是一个主要的健康问题。青春期使用的AA尤其令人震惊，因为青春期是成人行为模式的荷尔蒙敏感时期，而AAS使用的一种一致效果是增加攻击性。这项研究的目的是确定青少年AAS使用者的侵略性和冲动行为的因素，采用大鼠作为动物模型。拟议的研究将继续我们在AAS暴露的青春期男性方面的工作。目的我将确定早期的经验因素，这些因素可以预测在AAS处理的雄性中是否会增强攻击性。将研究早期暴露于5-羟色胺和社会征服的影响。将评估接触社会征服对5-羟色胺的影响。 AIM II将研究冲动性在AAS引起的攻击中的作用。第一个目标将采用我们开发的测试电池来衡量社交遭遇中的冲动性。该测试的一个优点是它在生物学上相关，不需要大量的培训或团队。在第二个实验中，将使用雄激素受体拮抗剂羟基氟氨酰胺确定AAS在介导冲动中的作用。在第三个实验中，使用SSRI氟西汀在AAS和性腺完整的大鼠中测试5-羟色胺在介导冲动中的作用。 AIM III将研究青春期AAS暴露的长期影响。第一个实验将确定青春期暴露于AAS暴露于AAS的男性低脑5-羟色胺的长期影响。第二个实验将确定在社会征服的男性中是否会增加侵略性行为，直到成年。在AIM IV中，我们将评估青春期AAS暴露的神经解剖学作用。由于性腺激素会影响树突状脊柱密度，因此我们将确定脊柱密度是否受到青春期期间AAS暴露的影响。内侧杏仁核和背侧海马中的脊柱密度将使用荧光染料DIL进行定量。青春期期间内源性激素环境的破坏可能导致不可逆转的行为和神经化学后果，并对成人行为模式产生长期的负面影响。通过将AAS暴露在发育中的神经系统上，这些研究将回答有关AAS使用对青春期大脑成熟和攻击行为的影响的重要问题。