Stress-induced increases of ethanol intake: The role of neuropeptide Y (NPY)
压力引起的乙醇摄入量增加:神经肽 Y (NPY) 的作用
基本信息
- 批准号:7686825
- 负责人:
- 金额:$ 2.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-08-05 至 2011-05-18
- 项目状态:已结题
- 来源:
- 关键词:AddressAlcohol abuseAlcohol consumptionAlcoholismAmygdaloid structureAnxietyAttenuatedBehaviorBloodBrain regionComplexEnvironmentEthanolExposure toHourHypothalamic structureInfusion proceduresInjection of therapeutic agentLabelLateralLeftLiteratureModelingMonitorMusMutant Strains MiceNeuropeptidesNeurotoxinsNoisePlayProceduresRecording of previous eventsRegulationRelapseRelative (related person)ResearchRodentRodent ModelRoleSalineScheduleSignal TransductionSiteSpecificityStressTestingTraumatic Stress Disordersbiological adaptation to stresscell killingdesigndrinkinginsightneuropeptide Yneuropeptide Y-Y1 receptornovelproblem drinkerreceptorreceptor functionresearch studyresponsestressortherapeutic target
项目摘要
DESCRIPTION (provided by applicant): Studies have shown that exposure to a stressor can increase ethanol consumption. One of the potential modulators of this effect is neuropeptide Y (NPY), which is involved in the regulation of both anxiety-like behavior and ethanol consumption in rodents. Thus, increased NPY signaling has been shown to reduce ethanol consumption and anxiety-like behaviors. The experiments described in the present proposal are designed to test the guiding hypothesis that NPY plays a protective role against stress-induced increases of ethanol consumption. All of the proposed studies will use a complex stressor, which consists of saline injections followed by simultaneous exposure to a novel environment and noise. Specific aim 1 will use mutant mice lacking NPY or the NPY Y1 receptor to determine the role of NPY signaling in stress-induced increases in ethanol consumption. Specific aim 2 will utilize a neurotoxin that is conjugated to NPY to target and kill cells expressing Y1 receptors. This neurotoxin allows the study of blunted NPY signaling in specific brain regions and aim 2 will determine the role of NPY signaling in the amygdala and the lateral hypothalamus on stress-induced increases in ethanol consumption. Specific aim 3 will study the effects of NPY signaling on limited access ethanol consumption in mice with or without prior exposure to a stressor. Specifically, mutant mice lacking NPY (or wild-type controls) with a prior history of stress exposure will be given access to ethanol for 2-4 hours/day, beginning 3 hours into the dark cycle. These procedures, labeled drinking-in-the-dark (DID), induce high levels of ethanol consumption and physiologically relevant blood ethanol concentrations and are thought to model binge-like ethanol drinking. Results from the proposed studies will provide insight on the importance of NPY signaling in modulating stress-induced increases of ethanol consumption. Since stress disorders are comorbid with alcoholism and as stress can trigger relapse in abstinent alcoholics, results from the present research may provide insight into potential therapeutic targets aimed at treated alcohol abuse and alcoholism.
描述(由申请人提供):研究表明,暴露于压力源会增加乙醇消耗。这种效应的潜在调节剂之一是神经肽 Y (NPY),它参与啮齿类动物焦虑样行为和乙醇消耗的调节。因此,增加 NPY 信号传导已被证明可以减少乙醇消耗和焦虑样行为。本提案中描述的实验旨在测试 NPY 对压力引起的乙醇消耗增加发挥保护作用的指导假设。所有拟议的研究都将使用复杂的压力源,其中包括注射盐水,然后同时暴露于新的环境和噪音。具体目标 1 将使用缺乏 NPY 或 NPY Y1 受体的突变小鼠来确定 NPY 信号在应激诱导的乙醇消耗增加中的作用。具体目标 2 将利用与 NPY 结合的神经毒素来靶向并杀死表达 Y1 受体的细胞。这种神经毒素可以研究特定大脑区域中钝化的 NPY 信号传导,目标 2 将确定杏仁核和外侧下丘脑中的 NPY 信号传导对压力引起的乙醇消耗增加的作用。具体目标 3 将研究 NPY 信号传导对先前暴露于或未暴露于压力源的小鼠的有限乙醇消耗的影响。具体来说,缺乏 NPY(或野生型对照)且先前有应激暴露史的突变小鼠将在进入黑暗周期 3 小时后每天摄入乙醇 2-4 小时。这些被称为“黑暗中饮酒”(DID)的程序会引起高水平的乙醇消耗和生理相关的血液乙醇浓度,并被认为是模拟暴饮暴食的乙醇饮酒。拟议研究的结果将深入了解 NPY 信号在调节应激引起的乙醇消耗增加中的重要性。由于压力障碍与酗酒并存,并且压力可能引发戒酒者的复发,因此本研究的结果可能有助于深入了解旨在治疗酒精滥用和酒精中毒的潜在治疗目标。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Angela M. Sparrow其他文献
Angela M. Sparrow的其他文献
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{{ truncateString('Angela M. Sparrow', 18)}}的其他基金
Stress-induced increases of ethanol intake: The role of neuropeptide Y (NPY)
压力引起的乙醇摄入量增加:神经肽 Y (NPY) 的作用
- 批准号:
7545140 - 财政年份:2008
- 资助金额:
$ 2.98万 - 项目类别:
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