Anabolic Androgenic Steroid Effects on Brain & Behavior

合成代谢雄激素类固醇对大脑的影响

• 批准号: 6546413
• 负责人: Marilyn Y MCGINNIS
• 金额: $ 25.43万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 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 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6546413
• 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 overall goal of this research is to understand the impact of peripubertal AAS abuse on sociosexual and reproductive maturation. This is an important area of AAS research in view of recent data indicating that AAS abuse has risen in teenagers. Critical hormonal and neurological changes occur during puberty which are responsible for the development and expression of aggressive, sexual and sociosexual behaviors. As human studies often rely on subjective reports, a rat model is used to study AAS effects on behavior. The aims of this project are to assess the behavioral and neuroendocrine consequences of AAS abuse in pubertal rats. Our work has focused on the individual effects of three commonly abused AAS, testosterone (TP), nandrolone (ND) and stanozolol (ST). In adults we found that TP stimulates aggression, and a phase advance in circadian rhythms. In contrast, ST suppresses aggression and sexual behavior. Because ST is not aromatizable, Aim 1 will determine whether the suppressive effect of ST on aggressive and reproductive behaviors is due to lack of estrogenic exposure. The results of this study will also demonstrate whether estrogen is required for development of sociosexual and aggressive behaviors in pubertal males. Aim 2 will assess whether the behavioral changes resulting from peripubertal AAS abuse are reversible. Since AAS users typically "stack" (combine) AAS, Aim 3 will determine whether 'stacking' ameliorates or exaggerates AAS effects on aggression and reproductive behavior. We previously found that TP induces an exaggerated response to physical provocation even toward non-threatening opponents. Aim 4 will examine whether this phenomenon extends to aggression toward females. Aim 5 will investigate whether serotonin plays a role in mediating AAS effects on aggression to delineate possible mechanisms underlying AAS effects on brain in juveniles. The fact that dynamic hormonal changes occur during puberty, and the brain is affected by these hormonal influences, emphasizes the need for more research on the effects of AAS exposure during adolescence.

描述（由申请人提供）：本研究的总体目标是了解青春期前后 AAS 滥用对社会性成熟和生殖成熟的影响。鉴于最近的数据表明青少年滥用 AAS 的现象有所增加，这是 AAS 研究的一个重要领域。青春期期间会发生关键的荷尔蒙和神经变化，导致攻击性行为、性行为和社会性行为的发展和表达。由于人类研究通常依赖于主观报告，因此使用大鼠模型来研究 AAS 对行为的影响。该项目的目的是评估青春期大鼠滥用 AAS 的行为和神经内分泌后果。我们的工作重点是三种常见滥用的 AAS：睾酮 (TP)、诺龙 (ND) 和康力龙 (ST) 的个体影响。在成年人中，我们发现 TP 会刺激攻击性，并使昼夜节律提前。相反，ST 抑制攻击性和性行为。由于 ST 不可芳香化，目标 1 将确定 ST 对攻击性和生殖行为的抑制作用是否是由于缺乏雌激素暴露所致。这项研究的结果还将证明青春期男性社会性行为和攻击性行为的发展是否需要雌激素。目标 2 将评估青春期前后 AAS 滥用导致的行为变化是否可逆。由于 AAS 用户通常“叠加”（组合）AAS，目标 3 将确定“叠加”是否会改善或夸大 AAS 对攻击性和繁殖行为的影响。我们之前发现，即使是针对没有威胁性的对手，TP 也会对身体挑衅产生夸张的反应。目标 4 将检查这种现象是否延伸到对女性的攻击性。目标 5 将调查血清素是否在介导 AAS 对攻击性的影响中发挥作用，以描述 AAS 对青少年大脑影响的可能机制。事实上，青春期期间荷尔蒙会发生动态变化，并且大脑受到这些荷尔蒙的影响，这一事实强调需要对青春期期间 AAS 暴露的影响进行更多研究。