NEURAL AND BEHAVIORAL ACTIONS OF ANABOLIC STEROIDS

合成代谢类固醇的神经和行为作用

基本信息

批准号：
6603927
负责人：
ANN S. CLARK
金额：
$ 26.72万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-12-10 至 2005-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6603927
关键词：
GABA receptor androgen analog animal puberty behavioral /social science research tag brain mapping drug adverse effect estrus female fertility hormone regulation /control mechanism laboratory rat libido receptor binding sex behavior steroid hormone receptor

项目摘要

DESCRIPTION (Adapted From The Applicant's Abstract): The long-term objective of this project is to elucidate the neural and behavioral actions of anabolic-androgenic steroid(s) (AAS). Although the majority of published research focuses on males, it has been shown that women and adolescent girls take AAS to improve athletic performance and to achieve a muscular physique. We have demonstrated that individual AAS have discrete and quantifiable effects on the estrous cycle and sexual receptivity in adult rats. The goal of the present proposal is to extend our analysis of AAS effects to include motivation for sexual behavior and to delineate the physiological mechanisms by which AAS affect the nervous system in female rats. First, we will broaden our analysis of AAS effects on female sexual behavior and physiology and address the following questions: (a) does prepubertal AAS administration alter the onset of puberty and produce short- or long-term changes in estrous cyclicity or fertility, (b) do AAS given in combination act synergistically or antagonistically to alter the estrous cycle or sexual behavior, and (c) do AAS alter sexual behaviors that underlie motivation that may be comparable to libido in humans? Second, we will test the role of three brain areas (ventromedial hypothalamus, preoptic area, and lateral septum) rich in androgen and estrogen receptors, in the inhibition of sexual behavior by AAS. Specifically, (a) does direct application of AAS to these brain regions produce effects on behavior that mimic systemic administration, and (b) does the ability of AAS to modulate sexual behaviors at these central sites depend on signaling through steroid (androgen or estrogen) receptors? Third, we will test the possibility that AAS may alter sexual behaviors by acting at gamma-aminobutyric acid type A (GABAa) receptors, because transmission mediated by the GABAergic system is known to modulate sexual behavior. Expressly, does the central administration of AAS modulate sexual behaviors via effects on neuroendocrine processes underlying the AAS modulation of female sexual behavior. Characterizing AAS effects on the central nervous and endocrine systems in laboratory animals will provide valuable scientific evidence that will improve our understanding not only of the physiological and behavioral responses to high dose AAS abuse in women, but also to other naturally occurring disorders that are accompanied by androgen excess, such as polycystic ovarian syndrome.

描述（根据申请人的摘要改编）：该项目的长期目标是阐明神经和合成代谢 - 基因类固醇（S）（AAS）的行为作用。虽然大多数已发表的研究都侧重于男性，已经表明妇女青少年女孩以AAS来提高运动表现并取得肌肉体质。我们已经证明了个体AA具有离散和对成年大鼠的发情周期和性接受能力的可量化影响。本提案的目的是将我们对AAS效应的分析扩展到包括性行为的动力并描述生理 AA会影响雌性大鼠神经系统的机制。首先，我们将扩大我们对AA对女性性行为影响的分析，并生理学和解决以下问题：（a）确实是AAS 管理改变青春期的发作并产生短期或长期发情循环或生育能力的变化，（b）在联合法中给出的AA 协同或拮抗以改变发情循环或性行为，（c）AAS改变了性行为，这是动力的基础可能与人类的性欲相媲美？其次，我们将测试三个角色大脑区域（腹侧下丘脑，前区域和外侧隔膜）丰富在雄激素和雌激素受体中，抑制性行为 AAS。具体而言，（a）将AAS直接应用于这些大脑区域对模仿系统给药的行为产生影响，（b）确实 AAS在这些中心站点调节性行为的能力取决于在通过类固醇（雄激素或雌激素）受体的信号传导上？第三，我们会的测试AA可以通过行动改变性行为的可能性 γ-氨基丁酸A型（GABAA）受体，因为透射介导已知通过GABA能系统调节性行为。明确，这样做 AAS的中央管理通过对性行为调节性行为 AAS aas性aas性a的神经内分泌过程行为。表征AAS对中枢神经和内分泌的影响实验动物中的系统将提供有价值的科学证据不仅会提高我们对生理和行为的理解对女性中高剂量AA滥用的反应，但也自然而然发生伴有雄激素过量的疾病，例如多囊卵巢综合征。