Effects of Acute and Chronic Alcohol on Brain Reward in Mice
急性和慢性酒精对小鼠大脑奖赏的影响
基本信息
- 批准号:7793038
- 负责人:
- 金额:$ 32.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-02-01 至 2014-01-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAgonistAlcohol abuseAlcohol consumptionAlcohol dependenceAlcohol withdrawal syndromeAlcoholic BeveragesAlcoholismAlcoholsAmericanAmericasAmphetaminesAnimalsBehaviorBehavioralBiologicalBlood alcohol level measurementBrainChemosensitizationChronicCocaineComplexConsumptionDBA/2 MouseDataDevelopmentDietary AlcoholDiseaseDopamineDopamine D2 ReceptorDopaminergic AgentsDoseDrug KineticsGeneticHeavy DrinkingImpairmentInbred Strains MiceInterventionLaboratoriesLeadMeasuresMediatingMethodsMotivationMouse StrainsMusNicotineOpiatesOralOral AdministrationOutcomePainPathway interactionsPharmaceutical PreparationsPhasePropertyPublic HealthRegulationRewardsRiskRodent ModelRoleScienceSelf AdministrationSelf StimulationSelf-AdministeredSignal TransductionSystemTaste PerceptionTestingThirstTimeTranslatingUnited StatesWithdrawaladdictionalcohol effectalcohol exposurealcohol rewardalcohol sensitivityalcohol use disorderbasecostdrinkingeffective therapyfallsgenetic straininsightmouse modelneural circuitnew therapeutic targetnovel strategiespublic health relevancereceptorreinforcerresearch studysocialsound
项目摘要
DESCRIPTION (provided by applicant): Alcohol use disorders and alcoholism are complex behavioral and biological endpoints that begin with the pleasurable, rewarding effects of initial alcohol use. Although many overlapping brain mechanisms contribute to addiction, mechanisms of reward and motivation are among the most salient targets of all addictive or compulsive disorders. To better understand what motivates excessive alcohol consumption, and thereby develop more effective strategies for intervention, a more thorough understanding of the relationship between alcohol and biological mechanisms of reward is important. This proposal will focus on the rewarding properties of alcohol in mouse models. Intracranial self-stimulation (ICSS) is a behavioral method used in animal studies that has made major contributions to our understanding of cocaine, amphetamine, opiate and nicotine reward. However, the application of ICSS to the study of alcohol reward has been comparatively limited, and the effects of alcohol on brain stimulation-reward (BSR) have not been studied in mouse models where genetic differences can more easily be evaluated. The main advantage of ICSS over other operant behavioral methods in which the animal must perform a task in order to receive a drug reinforcer (action->outcome) is that the rewarding effect of a drug is measured independent of the motivation of the animal to seek or consume the drug. Alcohol self-administration in rodent models may be complicated by factors such as taste aversion and thirst that are avoided with ICSS, which allows a unique and novel approach to investigate the genetic and pharmacological regulation of alcohol reward. Preliminary studies in our laboratory have shown that alcohol potentiates the rewarding value of BSR after acute administration by oral gavage in both C57BL6/J and DBA/2 mice. Genetic factors represent about half of the risk for alcohol dependence, and our preliminary data have established clear genetic differences in alcohol reward between these two mouse strains: alcohol doses lower than 1 g/kg potentiate BSR while doses higher than 1 g/kg depreciate BSR in C57BL6/J mice, a strain that voluntarily consumes alcohol. In contrast, DBA/2 mice show a robust, dose-dependent potentiation of BSR at doses up to 2.4 g/kg but do not voluntarily consume alcohol. The rewarding effect of alcohol is greatest at early time points (15-30 minutes) and coincides with the peak blood alcohol concentration (BAC) after oral administration in both strains, supporting the idea that animals find the rising phase of the BAC curve more pleasurable or rewarding than the falling phase. Experiments are proposed to further elucidate the pharmacokinetics and pharmacological effects of acute alcohol administration; to investigate adaptations to alcohol reward with intermittent or chronic alcohol exposure; and to determine the contribution of dopaminergic mechanisms to alcohol reward. Understanding the role of reward in alcohol dependence will clarify mechanisms of increased drinking liability and lead to insights into novel therapeutic targets that modify consumption by changing alcohol reward.
PUBLIC HEALTH RELEVANCE: The behavioral and biological problems of alcohol abuse begin with the pleasurable or rewarding effects of alcohol use. Alcohol use disorders are a major public health problem, costing American taxpayers almost $200 billion each year. The development of new and effective treatments based on sound neuroscientific evidence is critical to address the pain and impairment these disorders bring to the nearly 10 million people who suffer from them in the United States of America.
描述(由申请人提供):酒精使用障碍和酒精中毒是复杂的行为和生物学终点,开始与最初的酒精使用的愉快,奖励的影响。虽然许多重叠的大脑机制有助于成瘾,但奖励和动机机制是所有成瘾或强迫性障碍最突出的目标之一。为了更好地了解是什么促使过度饮酒,从而制定更有效的干预策略,更深入地了解酒精和奖励的生物机制之间的关系是很重要的。这项提案将集中在小鼠模型中酒精的奖励特性。颅内自我刺激(ICSS)是一种用于动物研究的行为方法,对我们理解可卡因,安非他明,阿片和尼古丁奖励做出了重大贡献。然而,ICSS在酒精奖励研究中的应用相对有限,并且尚未在小鼠模型中研究酒精对大脑刺激奖励(BSR)的影响,因为在小鼠模型中可以更容易地评估遗传差异。ICSS相对于其他操作性行为方法的主要优点是,动物必须执行一项任务才能接受药物奖励(行动->结果),药物的奖励效果是独立于动物寻求或消耗药物的动机来测量的。在啮齿动物模型中,酒精自我给药可能会因ICSS避免的味觉厌恶和口渴等因素而变得复杂,这使得研究酒精奖励的遗传和药理学调节成为一种独特而新颖的方法。我们实验室的初步研究表明,酒精增强C57 BL 6/J和DBA/2小鼠经口灌胃急性给药后的BSR的奖励价值。遗传因素约占酒精依赖风险的一半,我们的初步数据已经确定了这两种小鼠品系之间酒精奖励的明显遗传差异:酒精剂量低于1 g/kg增强BSR,而剂量高于1 g/kg则降低C57 BL 6/J小鼠的BSR,这是一种自愿饮酒的品系。相比之下,DBA/2小鼠在高达2.4 g/kg的剂量下显示出稳健的剂量依赖性BSR增强,但不会自愿饮酒。酒精的奖励效应在早期时间点(15-30分钟)最大,并且与两种菌株口服给药后的血液酒精浓度(BAC)峰值一致,支持动物发现BAC曲线的上升阶段比下降阶段更令人愉快或奖励的想法。实验拟进一步阐明急性酒精给药的药代动力学和药理学作用;研究间歇性或慢性酒精暴露对酒精奖励的适应性;并确定多巴胺能机制对酒精奖励的贡献。了解奖励在酒精依赖中的作用将澄清饮酒倾向增加的机制,并导致对通过改变酒精奖励来改变消费的新治疗靶点的深入了解。
公共卫生相关性:酒精滥用的行为和生物学问题开始与酒精使用的愉快或奖励作用。酒精使用障碍是一个主要的公共卫生问题,每年花费美国纳税人近2000亿美元。根据可靠的神经科学证据开发新的有效治疗方法,对于解决这些疾病给美利坚合众国近1 000万人带来的痛苦和损害至关重要。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
C J MALANGA其他文献
C J MALANGA的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('C J MALANGA', 18)}}的其他基金
Effects of Acute and Chronic Alcohol on Brain Reward in Mice
急性和慢性酒精对小鼠大脑奖赏的影响
- 批准号:
8418776 - 财政年份:2010
- 资助金额:
$ 32.51万 - 项目类别:
Effects of Acute and Chronic Alcohol on Brain Reward in Mice
急性和慢性酒精对小鼠大脑奖赏的影响
- 批准号:
8015614 - 财政年份:2010
- 资助金额:
$ 32.51万 - 项目类别:
Effects of Acute and Chronic Alcohol on Brain Reward in Mice
急性和慢性酒精对小鼠大脑奖赏的影响
- 批准号:
8215758 - 财政年份:2010
- 资助金额:
$ 32.51万 - 项目类别:
Effect of prenatal cocaine exposure on brain reward
产前接触可卡因对大脑奖赏的影响
- 批准号:
7231401 - 财政年份:2003
- 资助金额:
$ 32.51万 - 项目类别:
Effect of prenatal cocaine exposure on brain reward
产前接触可卡因对大脑奖赏的影响
- 批准号:
6611568 - 财政年份:2003
- 资助金额:
$ 32.51万 - 项目类别:
Effect of prenatal cocaine exposure on brain reward
产前接触可卡因对大脑奖赏的影响
- 批准号:
7123040 - 财政年份:2003
- 资助金额:
$ 32.51万 - 项目类别:
Effect of prenatal cocaine exposure on brain reward
产前接触可卡因对大脑奖赏的影响
- 批准号:
6891854 - 财政年份:2003
- 资助金额:
$ 32.51万 - 项目类别:
Effect of prenatal cocaine exposure on brain reward
产前接触可卡因对大脑奖赏的影响
- 批准号:
6791339 - 财政年份:2003
- 资助金额:
$ 32.51万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 32.51万 - 项目类别:
Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 32.51万 - 项目类别:
Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 32.51万 - 项目类别:
Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 32.51万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 32.51万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 32.51万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 32.51万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 32.51万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 32.51万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 32.51万 - 项目类别:
Research Grant