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Sex-Dependent Effect of Stress on Alcohol Consumption

压力对饮酒量的性别依赖性影响

基本信息

批准号：
8689389
负责人：
JUDITH E GRISEL
金额：
$ 36.1万
依托单位：
BUCKNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-05 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8689389
关键词：
Alcohol abuse Alcohol consumption Alcohol dependence Alcoholism Alcohols Animal Model Animals Anti-Anxiety Agents Applications Grants Automobile Driving Behavioral Biological Blood Brain Clinical Coping Behavior Corticosterone Corticotropin Data Data Analyses Dependence Development Empiricism Endocrine Endorphins Environment Environmental Risk Factor Etiology Excision Exercise Female Fostering Future Future Generations Gender Genetic Goals Gonadal Hormones Heavy Drinking Human Incentives Intervention Knowledge Laboratories Maintenance Male Castration Mediating Men&apos s Role Mentors Mind Mus Neural Pathways Neurosciences Neurosciences Research Operative Surgical Procedures Opioid Peptide Organism Ovariectomy Pathology Peer Review Peptides Physiological Predisposing Factor Prevalence Property Psychological reinforcement Publications Readiness Reporting Research Research Personnel Research Project Grants Rewards Risk Rodent Role Running Self Administration Self-Administered Sex Characteristics Stress Students Testing Training Transgenic Mice Underrepresented Minority Variant Work addiction alcohol effect alcohol reinforcement alcohol use disorder allostasis allostatic load base behavior test biological adaptation to stress career drinking drug reward endogenous opioids experience gonad function insight male meetings mouse model peptide E (adrenal medulla)pleasure preference problem drinker public health relevance reinforcer relating to nervous system research study response sedative sex skills stressor undergraduate student

项目摘要

DESCRIPTION (provided by applicant): The goal of this research is to better understand the influence of sex-dependent factors on the development of alcoholism. The overarching hypothesis is that there are sex differences in the liability toward alcohol abuse. More specifically, we hypothesize that sex differences partially derive from the effects of gonadal hormones and heritable levels of b-endorphin to influence the neural and behavioral stress response and modify the pleasure derived from alcohol (EtOH) administration. In Specific Aim 1, we will use mouse models to characterize the role of male versus female gonadal hormones in the effects of stress on EtOH self-administration. Our hypothesis here is that stress will increase the self-administration of EtOH, dependent upon gonadal hormones, such that an ovariectomy of female mice will counter this effect and that castration of male mice will promote it. Specific Aim 2 will focus on the role of b-endorphin (b-E) and endogenous opioid peptide in the sex-dependent effect of stress on the self-administration of EtOH. As differences in coping behavior and vulnerability to stress have a biological basis in HPA axis function and are modulated by b-E, we will use transgenic mice deficient in the capacity to synthesize b-E to test the hypothesis that behavioral responses contributing to allostasis of the stress response (i.e., EtOH self-administration) will vary as a function of this peptide. Finally, Specific Aim 3 is to employ at lest a dozen undergraduates, including female and underrepresented minority students, to work with the principle investigator on these research projects in a highly mentored environment. As an HHMI Distinguished Mentor with an exemplary record of collaborating with undergraduate students in the laboratory, the PI has a longstanding commitment to the educational benefit that these hands-on skills provide to future neuroscientists.

描述（由申请人提供）：本研究的目的是更好地了解性别依赖因素对酒精中毒发展的影响。最重要的假设是，酗酒的倾向存在性别差异。更具体地说，我们假设，性别差异部分来自性腺激素和遗传水平的b-内啡肽的影响，影响神经和行为的压力反应，并修改来自酒精（乙醇）管理的乐趣。在具体目标1中，我们将使用小鼠模型来表征雄性与雌性性腺激素在应激对EtOH自我给药的影响中的作用。我们的假设是压力会增加依赖于性腺激素EtOH的自我给药，因此雌性小鼠的卵巢切除术将抵消这种效应，雄性小鼠的阉割将促进这种效应。具体目标2将关注b-内啡肽（b-E）和内源性阿片肽在应激对EtOH自我给药的性别依赖性效应中的作用。由于应对行为和对压力的脆弱性的差异在HPA轴功能中具有生物学基础，并且受到b-E的调节，我们将使用合成b-E能力缺陷的转基因小鼠来测试有助于压力反应的别稳态的行为反应（即，EtOH自我给药）将作为该肽的函数而变化。最后，具体目标3是雇用至少12名本科生，包括女性和代表性不足的少数民族学生，在高度指导的环境中与这些研究项目的主要研究者合作。作为HHMI杰出导师，在实验室与本科生合作的典范记录，PI长期致力于这些实践技能为未来的神经科学家提供的教育效益。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

β-Endorphin and sex differentially modulate the response to EtOH in a site-specific manner.

β-内啡肽和性别以位点特异性方式差异调节对 EtOH 的反应。

DOI：
10.1016/j.brainres.2020.146845
发表时间：
2020
期刊：
Brain research
影响因子：
2.9
作者：
Rhinehart,ErinM;Waldron,Madison;Kelly-Quigley,Hannah;Zellers,McKenzie;Turco,Abby;Grisel,JudithE
通讯作者：
Grisel,JudithE

Sex differences in binge-like EtOH drinking, corticotropin-releasing hormone and corticosterone: effects of β-endorphin.