Project 2: Mechanisms underlying vulnerability to ethanol self-administration: behavioral and brain imaging studies in group-housed monkeys
项目 2:乙醇自我管理脆弱性的潜在机制:群养猴子的行为和大脑成像研究
基本信息
- 批准号:10310701
- 负责人:
- 金额:$ 39.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-12-10 至 2022-11-30
- 项目状态:已结题
- 来源:
- 关键词:AbstinenceAddressAlcohol consumptionAnimal ModelAnimalsAreaBehavioralBrainBrain imagingBrain regionCerebrovascular CirculationChronicConsultationsConsumptionCuesDataEthanolFunctional Magnetic Resonance ImagingGrantHourHumanHuman Subject ResearchImageIndividual DifferencesInterventionKnowledgeLaboratory AnimalsMacaca fascicularisMagnetic Resonance ImagingMediatingMediator of activation proteinModelingMonkeysNeurobiologyPatternPharmaceutical PreparationsPharmacologyPharmacotherapyPopulationPositioning AttributePrevention strategyPreventiveProceduresPublic HealthRelapseResistanceRestRodentScanningScheduleSelf AdministrationSocial HierarchyStimulantStressStructureStudy SubjectTestingTimeTranslationsVulnerable Populationsalcohol abstinencealcohol availabilityalcohol effectalcohol exposurealcohol reinforcementalcohol researchalcohol seeking behavioralcohol sensitivityalcohol use disorderbasebehavioral studychronic alcohol ingestioncostdrinkingdrug of abuseeffective therapyexperimental studyforestgray matterhuman subjectimaging modalityimaging studyinsightnonhuman primatenovelrelating to nervous systemresiliencesecondary analysissocialsocial groupsocial stresstherapy designtranslational approachtreatment effectwhite matter
项目摘要
PROJECT SUMMARY
Alcohol use disorder (AUD) persists as a costly public health problem that lacks widely effective medications
and strategies for prevention. The overarching scientific premise of this Project, like the others of the Wake
Forest Translational Alcohol Research Center (WF-TARC), is that the neural substrates that contribute to
vulnerability and resilience to AUD are not fully understood. Studies using nonhuman primate (NHP) subjects
have specific advantages that make them a critical part of a comprehensive, translational approach to
addressing this topic, including the possibility of experimental control not possible in human subjects and a
greater similarity to humans' neurobiology compared to rodents. Group-housed monkeys form linear social
hierarchies; social rank has been shown to influence sensitivity to abuse drugs, with subordinates showing
vulnerability to the abuse-related effects of stimulants and ethanol (EtOH). Project 2 of the WF-TARC will
exploit this differential sensitivity across social ranks to determine the behavioral and brain mechanisms that
underlie vulnerability to develop AUD. Behavioral studies will characterize rank-related differences in induction
of EtOH drinking, EtOH consumption over one year of 22 hours-per-day access and EtOH seeking behavior
during abstinence using an extremely well-characterized NHP EtOH self-administration model of long-term
drinking in humans. We will also determine whether dominant and subordinate monkeys differ in sensitivity to
chronic treatment potential medications for AUD. In parallel to these experiments, brain imaging studies using
magnetic resonance imaging will characterize the structural and functional differences between dominants and
subordinates, and determine the specific changes that occur in grey and white matter integrity, cerebral blood
flow and functional connectivity during long-term EtOH drinking and subsequent abstinence. Importantly, these
NHP studies occupy a critical position in the translational structure of the WF-TARC, supporting forward and
backwards translation to inform and extend findings in rodent and human projects. NHP imaging studies will
focus on the same brain regions and nodes that will be imaged in human subjects and studied and
manipulated in rodents. Secondary analyses on imaging data will expand this focus to the entire brain. Taken
together, the results of the studies in this Project, particularly in combination with data generated in other
components of the WF-TARC, will provide a comprehensive account of brain differences between populations
that are resistant versus vulnerable to AUD. This knowledge will ultimately help practitioners direct preventive
efforts to groups who will most benefit from them, and will identify new targets for more effective medications
targeted to the most vulnerable populations.
项目总结
酒精使用障碍(AUD)仍然是一个代价高昂的公共健康问题,缺乏广泛有效的药物
以及预防的策略。这个项目的主要科学前提,就像《觉醒》中的其他项目一样
森林转化酒精研究中心(WF-TARC),是神经底物对
对澳元的脆弱性和复原力还没有完全了解。非人灵长类(NHP)受试者的研究
具有特定的优势,使其成为全面、可转换的方法的关键部分
解决这个话题,包括在人类受试者中不可能的实验控制的可能性和一个
与啮齿动物相比,它与人类的神经生物学更相似。群居猴子形成线性社会
等级制度;社会等级已被证明影响对滥用药物的敏感性,下属表现出
易受兴奋剂和乙醇滥用相关影响的影响(乙醇)。WF-TARC的项目2将
利用这种社会阶层之间的差异敏感性来确定行为和大脑机制
开发AUD的潜在漏洞。行为研究将表征归纳中与职级相关的差异
酒精饮用量、一年以上每天饮用酒精22小时及酒精寻觅行为
在戒酒期间使用一种极具特色的NHP Etoh长期自我给药模式
在人类中饮酒。我们还将确定主猴和从属猴对
AUD的慢性治疗潜在药物。在这些实验的同时,大脑成像研究使用
磁共振成像将表征优势种和非优势种之间的结构和功能差异
并确定在灰质和白质完整性、脑血液中发生的具体变化
长期饮用乙醇和随后戒酒期间的流动和功能连接。重要的是,这些
NHP研究在WF-TARC的翻译结构中占有关键地位,支持向前和
向后翻译以通知和扩展啮齿动物和人类项目的研究结果。NHP成像研究将
将重点放在相同的大脑区域和节点上,这些区域和节点将在受试者身上成像并进行研究和
在啮齿动物身上被操控。对成像数据的二次分析将把这一重点扩展到整个大脑。已被占用
总而言之,本项目的研究结果,特别是结合其他项目产生的数据
WF-TARC的组成部分,将全面说明不同人群之间的大脑差异
对澳元具有抵抗力和脆弱性的人。这一知识最终将帮助实践者指导预防
向受益最大的群体努力,并将为更有效的药物确定新的靶点
针对最脆弱的人群。
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)
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Paul W. Czoty其他文献
Effects of chronic alcohol consumption on cocaine self-administration in rhesus monkeys
- DOI:
10.1016/j.drugalcdep.2014.09.161 - 发表时间:
2015-01-01 - 期刊:
- 影响因子:
- 作者:
Paul W. Czoty - 通讯作者:
Paul W. Czoty
Effect of menstrual phase and social stress on cognitive performance of female monkeys
- DOI:
10.1016/j.drugalcdep.2014.09.365 - 发表时间:
2015-01-01 - 期刊:
- 影响因子:
- 作者:
Sarah A. Kromrey;Paul W. Czoty;Michael A. Nader - 通讯作者:
Michael A. Nader
Effects of the dopamine D3/D2 receptor antagonist buspirone on food/cocaine choice in socially housed male cynomolgus monkeys
- DOI:
10.1016/j.drugalcdep.2014.09.144 - 发表时间:
2015-01-01 - 期刊:
- 影响因子:
- 作者:
Michael Coller;Paul W. Czoty;Michael A. Nader - 通讯作者:
Michael A. Nader
Dopamine D3 receptor availability: Sex differences and effects of chronic drug exposure
- DOI:
10.1016/j.drugalcdep.2014.09.442 - 发表时间:
2015-01-01 - 期刊:
- 影响因子:
- 作者:
Susan Martelle;Susan H. Nader;Paul W. Czoty;William S. John;Amy H. Newman;Michael A. Nader - 通讯作者:
Michael A. Nader
Influence of reproductive hormones on social rank and vulnerability to cocaine reinforcement in female cynomolgus monkeys
- DOI:
10.1016/j.drugalcdep.2015.07.331 - 发表时间:
2015-11-01 - 期刊:
- 影响因子:
- 作者:
Sarah Kromrey;Paul W. Czoty;Michael A. Nader - 通讯作者:
Michael A. Nader
Paul W. Czoty的其他文献
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{{ truncateString('Paul W. Czoty', 18)}}的其他基金
NOP Receptors in nonhuman primate models of AUD
AUD 非人灵长类动物模型中的 NOP 受体
- 批准号:
10386932 - 财政年份:2020
- 资助金额:
$ 39.86万 - 项目类别:
NOP Receptors in nonhuman primate models of AUD
AUD 非人灵长类动物模型中的 NOP 受体
- 批准号:
10608164 - 财政年份:2020
- 资助金额:
$ 39.86万 - 项目类别:
NOP Receptors in nonhuman primate models of AUD
AUD 非人灵长类动物模型中的 NOP 受体
- 批准号:
9885081 - 财政年份:2020
- 资助金额:
$ 39.86万 - 项目类别:
NOP Receptors in nonhuman primate models of AUD
AUD 非人灵长类动物模型中的 NOP 受体
- 批准号:
10212896 - 财政年份:2020
- 资助金额:
$ 39.86万 - 项目类别:
Project 2: Mechanisms underlying vulnerability to ethanol self-administration: behavioral and brain imaging studies in group-housed monkeys
项目 2:乙醇自我管理脆弱性的潜在机制:群养猴子的行为和大脑成像研究
- 批准号:
10526644 - 财政年份:2017
- 资助金额:
$ 39.86万 - 项目类别:
Interactions of Ethanol & Cocaine Self-Administration in Monkeys
乙醇的相互作用
- 批准号:
9502948 - 财政年份:2016
- 资助金额:
$ 39.86万 - 项目类别:
Interactions of Ethanol & Cocaine Self-Administration in Monkeys
乙醇的相互作用
- 批准号:
9175685 - 财政年份:2016
- 资助金额:
$ 39.86万 - 项目类别:
Brain imaging and cognitive effects of cocaine self-administration in monkeys
猴子自我注射可卡因的脑成像和认知效应
- 批准号:
7867262 - 财政年份:2010
- 资助金额:
$ 39.86万 - 项目类别:
Cocaine discrimination, self-administration and microdialysis in monkeys
猴子可卡因歧视、自我给药和微透析
- 批准号:
7877863 - 财政年份:2007
- 资助金额:
$ 39.86万 - 项目类别:
Cocaine discrimination, self-administration and microdialysis in monkeys
猴子可卡因歧视、自我给药和微透析
- 批准号:
7259129 - 财政年份:2007
- 资助金额:
$ 39.86万 - 项目类别:
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