Vasopressin Signaling in Pain and Alcohol Dependence
疼痛和酒精依赖中的加压素信号传导
基本信息
- 批准号:9761937
- 负责人:
- 金额:$ 33.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-10 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AbstinenceAffectiveAlcohol dependenceAlcohol withdrawal syndromeAlcoholsAmygdaloid structureAnimal ModelAnimalsAreaAutomobile DrivingBehaviorBrainBrain regionChronicClinicalDependenceEthanolFemaleGene ExpressionGene Expression ProfilingGenetic TranscriptionGlucocorticoid ReceptorGlucocorticoidsHeavy DrinkingHumanHyperalgesiaHypersensitivityIndividualInvestigationLinkMeasuresMechanicsModelingMotivationNegative ReinforcementsNeuropeptidesNociceptionPainPersistent painPharmaceutical PreparationsPharmacologyPhosphoproteinsPhosphorylationPropertyPsychological reinforcementRattusReceptor SignalingRodentRoleSeveritiesSex DifferencesSignal TransductionSiteStressSystemVasopressin ReceptorVasopressinsWomanWorkalcohol exposurealcohol reinforcementalcohol use disordercentral painchronic paindrinkingeffective therapyemotional symptomexperienceinnovationinsightmalemennegative emotional stateneuroadaptationneurobiological mechanismnovelpain reductionpain sensitivitypain symptompre-clinicalreceptorresponsesextherapeutic targetvapor
项目摘要
Project Summary ______
Alcohol use disorder (AUD) is associated with the emergence of negative emotional states that can influence
the motivational properties of alcohol. Pain represents one such motivational state hypothesized to drive AUD
severity (Egli, Koob, and Edwards, 2012), and this relationship is particularly concerning since there are limited
treatments for either chronic pain or AUD. Ascending nociceptive circuitry and excessive alcohol exposure
alters the function of central brain stress and reinforcement systems, including the central amygdala (CeA).
Related neuroadaptations may underlie negative reinforcement mechanisms driven by persistent pain in the
context of AUD. We have discovered the emergence of a significant mechanical and thermal nociceptive
hypersensitivity (or hyperalgesia) in alcohol-dependent male rats and our current aim is to interrogate valid
animal models of excessive drinking and hyperalgesia toward the elucidation of neuropharmacological
mechanisms contributing to these conditions in alcohol dependence. Our previous work implicated the stress
neuropeptide vasopressin in the transition to dependence in male rats via its actions on V1b receptors (V1bRs;
Edwards et al., 2012). While V1bR antagonists reduce excessive drinking in rodents and facilitate abstinence
in alcohol-dependent individuals (Ryan et al., 2016), additional evidence suggests that they may also reduce
stress-induced hyperalgesia (Bradesi et al., 2009). Pain-related affective responses are also enhanced via
vasopressin signaling through CeA V1a receptors (V1aRs, Cragg et al., 2016), although the contribution of this
receptor system to excessive drinking or hyperalgesia in the context of alcohol dependence is unexplored. As
two key stress-regulatory systems, vasopressin and glucocorticoid signaling may closely interact, with each
system driving the other's activity in a bidirectional fashion. Elucidation of this link could be critical to
understanding the efficacy of glucocorticoid receptor antagonist therapy in reducing excessive drinking in
preclinical and clinical models (Vendruscolo et al., 2015). Our primary hypothesis is that blockade of either of
two subclasses of central vasopressin receptors (V1bRs or V1aRs) in a key pain- and reinforcement-related
brain area (CeA) will reduce both excessive drinking and hyperalgesia in alcohol-dependent animals. Our
secondary hypothesis is that blockade of vasopressin V1bR signaling will reduce GR phosphorylation in the
CeA of alcohol-dependent animals, while blockade of GR transcription activity will also reduce vasopressin
system gene expression in the CeA. We also propose an investigation of sex as a factor in these relationships
given the substantial human sex differences in alcohol withdrawal and pain. A better understanding of the
central brain mechanisms of alcohol dependence-related behaviors (excessive drinking and hyperalgesia) will
provide substantial insight into neurobiological mechanisms of dependence and may reveal novel treatment
opportunities for AUD and persistent pain in the context of AUD.
项目总结______
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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Scott Edwards其他文献
Scott Edwards的其他文献
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{{ truncateString('Scott Edwards', 18)}}的其他基金
Interaction of Biopsychosocial Stress, Alcohol Misuse, and Neurobehavioral Sequelae of COVID-19
生物心理社会压力、酒精滥用和 COVID-19 神经行为后遗症的相互作用
- 批准号:
10686865 - 财政年份:2022
- 资助金额:
$ 33.08万 - 项目类别:
Interaction of Biopsychosocial Stress, Alcohol Misuse, and Neurobehavioral Sequelae of COVID-19
生物心理社会压力、酒精滥用和 COVID-19 神经行为后遗症的相互作用
- 批准号:
10471105 - 财政年份:2022
- 资助金额:
$ 33.08万 - 项目类别:
Vasopressin Signaling in Pain and Alcohol Dependence
疼痛和酒精依赖中的加压素信号传导
- 批准号:
10441221 - 财政年份:2018
- 资助金额:
$ 33.08万 - 项目类别:
Vasopressin Signaling in Pain and Alcohol Dependence
疼痛和酒精依赖中的加压素信号传导
- 批准号:
10189449 - 财政年份:2018
- 资助金额:
$ 33.08万 - 项目类别:
Role of GluA1 in the Escalation of Alcohol Drinking in Nicotine-Dependent Animals
GluA1 在尼古丁依赖动物饮酒量增加中的作用
- 批准号:
9456050 - 财政年份:2017
- 资助金额:
$ 33.08万 - 项目类别:
Intersection of Pain and Ethanol-Seeking Mechanisms in Ethanol Dependence
乙醇依赖中疼痛与乙醇寻求机制的交叉点
- 批准号:
8374254 - 财政年份:2012
- 资助金额:
$ 33.08万 - 项目类别:
Intersection of Pain and Ethanol-Seeking Mechanisms in Ethanol Dependence
乙醇依赖中疼痛与乙醇寻求机制的交叉点
- 批准号:
8786926 - 财政年份:2012
- 资助金额:
$ 33.08万 - 项目类别:
Role of Central Vasopressin/ERK Signaling in Ethanol Dependence
中枢加压素/ERK 信号在乙醇依赖中的作用
- 批准号:
7943923 - 财政年份:2009
- 资助金额:
$ 33.08万 - 项目类别:
Role of Central Vasopressin/ERK Signaling in Ethanol Dependence
中枢加压素/ERK 信号在乙醇依赖中的作用
- 批准号:
8123465 - 财政年份:2009
- 资助金额:
$ 33.08万 - 项目类别:
Role of Central Vasopressin/ERK Signaling in Ethanol Dependence
中枢加压素/ERK 信号在乙醇依赖中的作用
- 批准号:
7678680 - 财政年份:2009
- 资助金额:
$ 33.08万 - 项目类别:
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