Molecular Signatures of Social Stress-Induced Escalation of Drinking
社会压力引起饮酒增加的分子特征
基本信息
- 批准号:10667840
- 负责人:
- 金额:$ 23.81万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-05-20 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:Addictive BehaviorAlcohol consumptionAlcoholsAnimalsAnxietyArousalBehavioralBrain regionCandidate Disease GeneCell NucleusCellsCodeDatabasesDimensionsDiseaseDrug AddictionDrug usageEnterobacteria phage P1 Cre recombinaseEstrogen ReceptorsExposure toFOS geneFemaleFutureGene Expression ProfileGenesGeneticGenetic RecombinationGenetic TranscriptionGrantHumanHuman DevelopmentHypothalamic structureIn Situ HybridizationIndividualKnowledgeLabelLeadLibrariesMapsMediatingMental DepressionMental disordersMessenger RNAModelingMolecularMolecular ProfilingMotivationMusNeuronsNeurosecretory SystemsPathway AnalysisPathway interactionsPopulationProcessRNAReporterResolutionReverse TranscriptionRewardsRisk FactorsRodentRoleSignal TransductionSocial EnvironmentSocial InteractionSourceStressStressful EventStructure of paraventricular nucleus of thalamusSystemTestingThalamic structureTissue-Specific Gene Expressionaddictionalcohol exposurealcohol use disorderbehavioral responsecandidate identificationcell typedifferential expressiondrinkingdrug candidatedrug of abusedruggable targetexperienceexperimental studygene networkhigh rewardhigh riskinducible Cremalemotivated behaviormouse modelneuralneural circuitneuroadaptationneuromechanismneuropsychiatryparaventricular nucleuspreferencepreventprogramspromoterresponsesocialsocial defeatsocial stresssocial stressorstressortranscriptometranscriptomic profiling
项目摘要
Social stress is one of the most common forms of stress experienced by humans and has been well documented
to contribute to a wide variety of neuropsychiatric conditions. Exposure to repeated social defeat stress (SDS)
in rodents enhances the rewarding and reinforcing effects of several drugs of abuse, including alcohol, and is a
reliable predictor of future drug use. SDS is effectively modeled in animals through social defeat paradigms,
where an antagonistic encounter is initiated between two animals of the same species. There is substantial
overlap between brain regions that mediate the behavioral response to stressors and those that mediate drug
addiction, implying shared neural circuitry. However, the precise neural mechanisms by which social stressors
increase alcohol consumption are not well understood. This application will address this gap in knowledge by
using a cell type agnostic approach to identify and profile the transcriptomes of cells that are activated by both
SDS and alcohol exposure at single cell resolution. Using the recently developed TRAP2 (Targeted
Recombination in Activated Populations) system and a mouse model for SDS-induced escalation of alcohol
drinking, we examined the overlap between neural ensembles that are activated by social stress and alcohol
consumption in the same animal. Our preliminary results indicate that SDS increased alcohol consumption and
neuronal activation in the paraventricular thalamus (PVT) and the paraventricular nucleus of the hypothalamus
(PVN), brain regions known to mediate the motivational effects of stress. We found that both stress and alcohol
by themselves activate a large number of cells in the PVT and PVN. Interestingly, our results also indicate that
>80% of stress-activated cells are also activated by alcohol in these brain regions. Based on these results, we
hypothesize that transcriptional programs in cells that are activated by both stress and alcohol in the PVT and
PVN are unique compared to those that are activated by stress alone or alcohol alone and underlie stress-
induced escalation of alcohol consumption. We propose to use single nuclei sequencing to transcriptionally
profile cells in the PVT and PVN that are activated by both stress and alcohol. We will then identify genes,
pathways and processes that are dysregulated in these cells. We also propose to us the Library of Integrated
Cellular Signatures (LINCs) to identify compounds that will reverse these transcriptional signatures and are thus
predicted to prevent stress-induced escalation of alcohol consumption.
社会压力是人类经历过的最常见的压力形式之一,并且有很好的记录
项目成果
期刊论文数量(0)
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Rajani Maiya其他文献
Rajani Maiya的其他文献
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{{ truncateString('Rajani Maiya', 18)}}的其他基金
Role of the transcriptional regulator Lmo4 in alcohol consumption and reward
转录调节因子 Lmo4 在饮酒和奖励中的作用
- 批准号:
10268581 - 财政年份:2019
- 资助金额:
$ 23.81万 - 项目类别:
Role of the transcriptional regulator Lmo4 in alcohol consumption and reward
转录调节因子 Lmo4 在饮酒和奖励中的作用
- 批准号:
10322460 - 财政年份:2019
- 资助金额:
$ 23.81万 - 项目类别:
Role of the transcriptional regulator Lmo4 in alcohol consumption and reward
转录调节因子 Lmo4 在饮酒和奖励中的作用
- 批准号:
10544351 - 财政年份:2019
- 资助金额:
$ 23.81万 - 项目类别:
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