NEURAL AND BEHAVIORAL ACTIONS OF ANABOLIC STEROIDS

这个项目的长期目标是阐明神经和 合成代谢雄激素类固醇（AAS）的行为作用。AAS是 合成的雄激素样化合物， 运动员的意图，以提高他们的肌肉外观， 力量和/或运动表现。AAS的滥用已成为一个主要的 药物滥用问题。AAS已被证明具有 对肝脏、心血管和内分泌产生严重不良影响 系统. AAS也已知会产生严重和有害的变化， 情感与行为的关系，但目前，很少有系统的研究 已经评估了AAS对中枢神经系统或行为的影响。 虽然内源性类固醇激素（例如，睾丸激素）已知 规范性行为和攻击，缺乏关于性行为的数据。 AAS的神经内分泌作用。尽管如此，病例报告清楚地表明， 需要这种知识，因为生殖功能的改变， 暴力行为的增加与AAS的使用有关。的 本提案的目的是调查AAS对 中枢神经系统集中在三个具体的问题。第一，如何 AAS对成年男性性行为及神经内分泌功能的影响 雌性老鼠？第二，AAS对显示器的影响是什么？ 成年雄性大鼠的攻击性这项研究计划的重点是 检查AAS对性行为、神经内分泌功能和 在性腺切除和性腺完整的动物中的攻击性。研究 AAS在性腺切除大鼠中的作用允许测定AAS 在没有性腺分泌物的情况下的行动，而AAS分析 在性腺完整的动物中的作用更接近于人类 条件和允许评估AAS和 内源激素拟议研究的第三个目标是 确定神经类固醇受体和AAS作用的大脑区域， 大脑使用多种策略。首先，AAS的竞争能力 与大脑中的雄激素、雌激素和皮质类固醇受体 评估。此外，AAS占据细胞核的程度 将对受体进行研究。最后，类固醇受体数量的变化 作为慢性AAS的结果， 将被审查。在所有研究中，将特别注意 分析特定类别的AAS的影响，这些AAS通常 虐待，并比较行为和生化反应， 不同剂量、给药方案和暴露于这些药物的持续时间 毒品综合起来，这些实验的结果将导致 更好地了解AAS对人类健康和行为的影响。

The long-term objective of this project is to elucidate the neural and behavioral actions of anabolic-androgenic steroids (AAS). AAS are synthetic androgen-like compounds which are taken in massive quantities by athletes with the intention of enhancing their muscular appearance, strength, and/or athletic performance. Abuse of AAS has become a major substance abuse problem in this country. AAS have been shown to have profound adverse effects on the liver, cardiovascular and endocrine systems. AAS are also known to produce severe and deleterious changes in affect and behavior, however, at the present time, few systematic studies have evaluated AAS effects on the central nervous system or behavior. Although endogenous steroid hormones (e.g., testosterone) are known to regulate sexual behavior and aggression, there is paucity of data on the neuroendocrine effects of AAS. Nonetheless, case reports clearly indicate the need for this knowledge, as alterations in reproductive function and an increase in violent behavior have been associated with AAS use. The goal of the present proposal is to investigate the effects of AAS on the central nervous system focusing on three specific questions. First, how do AAS influence sexual behavior and neuroendocrine function in adult male and female rats? Second, what is the impact of AAS on the display of aggression in adult male rats? A focus of this research proposal is to examine the effects of AAS on sexual behavior, neuroendocrine function and aggression in both gonadectomized and gonadally intact animals. Studies of AAS action in the gonadectomized rat allow for the determination of AAS actions in the absence of gonadal secretions, while analyses of AAS effects in the gonadally intact animal more closely mimic the human condition and permit evaluation of the interactions between AAS and endogenous hormones. The third goal of the proposed research is to determine the neural steroid receptors and brain areas at which AAS act in the brain using several strategies. First, the ability of AAS to compete with brain androgen, estrogen and corticosteroid receptors will be assessed. In addition, the extent to which AAS occupy cell nuclear receptors will be explored. Finally, changes in steroid receptor number which occur within specific brain areas as a consequence of chronic AAS will be examined. In all studies, special attention will be given to analyzing the effects of specific classes of AAS which are commonly abused, and comparing the behavioral and biochemical responses to different doses, dosing regimens, and durations of exposure to these drugs. Taken together, the results from these experiments will lead to a better understanding of the impact of AAS on human health and behavior.