The DNA methylation code governing the ensemble representation of morphine-context association
DNA甲基化密码控制吗啡-背景关联的整体表示
基本信息
- 批准号:9906873
- 负责人:
- 金额:$ 21.14万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-15 至 2021-03-31
- 项目状态:已结题
- 来源:
- 关键词:AbstinenceAcuteAddressAllelesBehaviorBrain regionCellsChronicClinicalCodeDNA MethylationDataDevelopmentDigit structureDrug usageEconomicsElectrophysiology (science)EnhancersEnvironmentEpigenetic ProcessExposure toFutureGene ExpressionGene Expression AlterationGenesGenetic TranscriptionGoalsHippocampus (Brain)IncidenceInvestigationLinkMaintenanceMediatingMemoryMethylationModelingMorphineMorphine DependenceMorphologyNeuronsNucleus AccumbensOpiate AddictionOpioidOpioid AnalgesicsPharmaceutical PreparationsPlayPopulationPropertyRelapseReportingRewardsRisk FactorsRoleSeriesSignal TransductionSliceSocial ProblemsSubstance Use DisorderSynapsesUnited StatesWithdrawal SymptomWorkaddictiondigitaldrug cravingdrug developmentdrug of abusedrug relapsedrug seeking behavioreffective therapyentorhinal cortexepigenomicsexperienceexperimental studyhigh riskhippocampal pyramidal neuroninnovationmemory recallmethylomemorphine administrationneural circuitneuronal circuitrynonmedical useopioid misuseopioid use disorderpostsynapticpredictive modelingpreferencepreventrecruitrelating to nervous system
项目摘要
Abstract
Morphine is a widely-prescribed and potent opioid analgesic, but in recent years its non-medical use has
been on the rise and has contributed to the increased incidence of opioid use disorder. Repeated exposure
to morphine and other drugs of abuse leads to lasting learned associations between the rewarding
properties of the drug and the environment of administration. Therefore even in abstinence, re-exposure to
the context is a risk factor for relapse, increasing withdrawal symptoms and drug cravings. While the
neural circuits mediating drug-context associations and drug seeking behavior have been studied heavily,
the specific underlying mechanisms of these associations remain poorly understood. In the proposed
studies, we aim to evaluate the hypothesis that epigenetic alterations in the methylation of genes related to
neuronal connectivity and excitability during repeated morphine-context pairings provide a mechanism for
the stable recruitment of a small, specific population of neurons in the ventral hippocampus to the
‘engram” storing the memory of morphine-context associations. Switching the methylation status of these
genes alters gene expression, which leads to increased excitability and connectivity with pre- and
postsynaptic circuit cortical and limbic partners to enhance the morphine-context association and create a
lasting memory. By characterizing the changes in methylation in the recruited hippocampal neuronal
ensemble and evaluating the consequent effects on neuronal function and circuit plasticity, our
experiments may provide a new framework for the study of the mechanisms of opioid addiction and
contribute to more effective treatments of substance use disorder.
摘要
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)
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Kristen Elizabeth Pleil其他文献
Kristen Elizabeth Pleil的其他文献
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{{ truncateString('Kristen Elizabeth Pleil', 18)}}的其他基金
A critical role for rapid estrogen signaling in alcohol addiction and anxiety
快速雌激素信号在酒精成瘾和焦虑中的关键作用
- 批准号:
10447201 - 财政年份:2019
- 资助金额:
$ 21.14万 - 项目类别:
A critical role for rapid estrogen signaling in alcohol addiction and anxiety
快速雌激素信号在酒精成瘾和焦虑中的关键作用
- 批准号:
10190744 - 财政年份:2019
- 资助金额:
$ 21.14万 - 项目类别:
The DNA methylation code governing the ensemble representation of morphine-context association
DNA甲基化密码控制吗啡-背景关联的整体表示
- 批准号:
9766748 - 财政年份:2019
- 资助金额:
$ 21.14万 - 项目类别:
A critical role for rapid estrogen signaling in alcohol addiction and anxiety
快速雌激素信号在酒精成瘾和焦虑中的关键作用
- 批准号:
10659024 - 财政年份:2019
- 资助金额:
$ 21.14万 - 项目类别:
A critical role for rapid estrogen signaling in alcohol addiction and anxiety
快速雌激素信号在酒精成瘾和焦虑中的关键作用
- 批准号:
10013109 - 财政年份:2019
- 资助金额:
$ 21.14万 - 项目类别:
The role of excitatory inputs to BNST CRF neurons in alcohol drinking behavior
BNST CRF 神经元兴奋性输入在饮酒行为中的作用
- 批准号:
8805040 - 财政年份:2015
- 资助金额:
$ 21.14万 - 项目类别:
The role of excitatory inputs to BNST CRF neurons in alcohol drinking behavior
BNST CRF 神经元兴奋性输入在饮酒行为中的作用
- 批准号:
9379322 - 财政年份:2015
- 资助金额:
$ 21.14万 - 项目类别:
The role of excitatory inputs to BNST CRF neurons in alcohol drinking behavior
BNST CRF 神经元兴奋性输入在饮酒行为中的作用
- 批准号:
9461824 - 财政年份:2015
- 资助金额:
$ 21.14万 - 项目类别:
The effect of alcohol drinking on NPY modulation of inhibition in the BNST
饮酒对 BNST 中 NPY 抑制调节的影响
- 批准号:
8469284 - 财政年份:2012
- 资助金额:
$ 21.14万 - 项目类别:
The effect of alcohol drinking on NPY modulation of inhibition in the BNST
饮酒对 BNST 中 NPY 抑制调节的影响
- 批准号:
8314809 - 财政年份:2012
- 资助金额:
$ 21.14万 - 项目类别:
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