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Role of gonadal hormones in HPA responses to alcohol administration in the rat

性腺激素在大鼠饮酒后 HPA 反应中的作用

基本信息

批准号：
8243640
负责人：
DANIEL SELVAGE
金额：
$ 23.01万
依托单位：
UNIVERSITY OF NEW ENGLAND
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-15 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8243640
关键词：
Adrenal Glands Adrenal hormone preparation Alcohol abuse Alcohol consumption Alcohols Animals Area Back Blood Circulation Brain Brain region Castration Cells Chemicals Diffuse Drug effect disorder Endocrine Estrogens Estrous Cycle Estrus FOS gene Feedback Female Fertility Gender Generations Genetic Transcription Glean Goals Gonadal Hormones Gonadal Steroid Hormones Grant Health Hormonal Hormone Receptor Hormones Hypothalamic structure Immediate-Early Genes In Situ Hybridization Investigation Laboratories Lead Link Measurable Mechanics Mediating Medical Methods Modeling Modification Nature Neuraxis Neurons Neurotransmitter Receptor Neurotransmitters Ovariectomy Peripheral Pharmaceutical Preparations Phenotype Pituitary Gland Pituitary-Adrenal System Play Population Progesterone Protein Isoforms Rattus Regulation Relative (related person)Research Role Safe Sex Sex Characteristics Sexual Development Site Staging Stimulus Stress Techniques Testing Testosterone Ventricular Woman Work addiction alcohol abuse therapy alcohol effect alcohol related problem alcohol response biological adaptation to stress design drug of abuse drug withdrawal feeding hydrophilicity immunocytochemistry lateral ventricle male men psychologic receptor research study response sex stressor

项目摘要

DESCRIPTION (provided by applicant): One of the main ways that alcohol causes health problems is by its actions on the hypothalamus-pituitary-adrenal (HPA) or "stress" axis. Interestingly, the HPA axes of males and females respond differently to stressors and to drugs like alcohol. The general hypothesis for the research proposed in this grant is that gonadal hormones such as estrogen and testosterone alter neuronal responsiveness to alcohol, resulting in sexually dimorphic HPA axis function. The long- term objective of the work is to elucidate the anatomical and functional neuronal machinery underlying sex- specific HPA responses to alcohol in rats. Increasing our understanding of the mechanisms responsible for sexually dimorphic HPA responses is imperative if gender- specific treatments for medical problems that arise with alcohol use and abuse are to be created. In order to highlight the role of the CNS in HPA activation by alcohol, the proposed experiments will use the relatiactions on the CNS. This model simplifies the study of strictly brain- mediated sex differences in HPA responses to alcohol by obviating the noxious peripheral actions of the drug that feed back to the brain and alter its function in a non-specific manner. Such feedback dramatically increases HPA activity, and tremendously complicates the study of sex differences in HPA responses to alcohol. Studies for Specific Aim 1 will investigate the mechanisms underlying sex differences in HPA- linked neuronal responses to alcohol administration. This work will first focus on identifying specific brain regions responsive to alcohol, involved in the regulation of the HPA axis, and sensitive to gonadal hormones. We will then probe the functional roles of specific gonadal hormones and their receptors in regulating neuronal activation relevant to HPA function. Studies for Specific Aim 2 will investigate the mechanisms by which gonadal steroids and their receptors interact to cause sex- dependent serug has different effects on the two sexes. The purpos of the proposed project is to investigate the basic central nervous system mechanisms that generate potentially harmful, sex- specific responses to alcohol formation can then be used to develop sex- related treatments for alcohol- related health problems. PUBLIC HEALTH RELEVANCE: Alcohol use causes detrimental health effects in both men and women. Interestingly, the d

描述(申请人提供)：酒精引起健康问题的主要方式之一是它对下丘脑-垂体-肾上腺(HPA)或“压力”轴的作用。有趣的是，男性和女性的HPA轴对压力源和酒精等药物的反应不同。这项研究的一般假设是，性腺激素，如雌激素和睾丸素，改变了神经元对酒精的反应，导致了性二态HPA轴的功能。这项工作的长期目标是阐明大鼠对酒精的性别特异性HPA反应背后的解剖和功能神经机制。如果要为酒精使用和滥用引起的医疗问题创造针对性别的治疗，就必须增加我们对导致性二相性HPA反应的机制的理解。为了强调中枢神经系统在酒精激活HPA中的作用，本实验将使用中枢神经系统上的相关作用。这个模型简化了严格由大脑调节的HPA对酒精反应的性别差异的研究，因为它排除了药物的有害外周动作，这些外周动作反馈到大脑，并以非特异性的方式改变其功能。这种反馈极大地增加了HPA的活性，并极大地复杂化了HPA对酒精反应的性别差异的研究。针对特定目标1的研究将探讨酒精对HPA相关神经元反应的性别差异的潜在机制。这项工作首先将专注于确定特定的大脑区域，这些区域对酒精做出反应，参与调节HPA轴，并对性腺激素敏感。然后，我们将探讨特定性腺激素及其受体在调节与HPA功能相关的神经元激活中的功能作用。针对特定目的的研究2将探讨性腺类固醇及其受体相互作用导致性别依赖血清对两性产生不同影响的机制。这项提议的项目的目的是研究产生潜在有害的、针对性别的酒精反应的中枢神经系统的基本机制。