Understanding neuronal subtype-specific function of NAc in cocaine addiction
了解 NAc 在可卡因成瘾中的神经元亚型特异性功能
基本信息
- 批准号:10115270
- 负责人:
- 金额:$ 76.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-01 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:AbstinenceAnimal BehaviorBehavioralBrainBrain DiseasesBrain regionCell NucleusCellsCessation of lifeChronicCocaineCocaine DependenceCoupledDataDevelopmentDiseaseDrug AddictionEnzymesEpigenetic ProcessGene Expression ProfileGene Expression ProfilingGenetic TranscriptionGoalsHealthHeterogeneityHumanIntravenousLabelMediatingMental disordersModelingMolecularMotivationMusNational Institute of Drug AbuseNeuronsNucleus AccumbensPharmaceutical PreparationsPhasePlayProcessPsychological reinforcementRegulationRelapseRewardsRoleSalineSelf AdministrationSystemTherapeutic InterventionTissue-Specific Gene ExpressionUnited StatesViraladdictionbasebrain cellcell typeclinically relevantcocaine self-administrationcostdrug of abuseepigenetic profilingexperimental studygenetic approachknock-downmouse modelneural circuitneuronal circuitrynew therapeutic targetoverexpressionrelapse risksingle-cell RNA sequencingsocialtargeted treatmenttranscriptomeweb site
项目摘要
Understanding neuronal subtype-specific function of NAc in cocaine addiction
Abstract
Drug addiction is a chronic, relapsing brain disorder characterized by compulsive drug seeking
and use despite harmful consequences. It is an urgent social and health problem contributing to more
than 90,000 deaths and incurs a yearly cost of over $700 billion in the United States (see NIDA website).
It is believed that long-term maladaptive changes in the brain reward system play a central role in the
development of addictive disorders. However, the underlying mechanism remains largely unknown.
The long-lasting effect of drugs on animal behavior and the risk of relapse in human addicts
indicate that some stable changes in the brain reward system induced by drugs of abuse mediate these
long-term behavioral adaptions. Accumulating evidence suggests that drug-induced molecular, cellular
and circuitry changes, especially those in the nucleus accumbens (NAc), play important roles in drug
addiction. However, due to the cellular heterogeneity of the mammalian brain, the cell type-specific
mechanism of addition is unknown.
To overcome the cell heterogeneity issue and to advance our understanding of the cell subtype-
specific mechanisms of drug addiction, we propose to identify the neuronal subtypes in NAc involved
in addiction by comprehensively analyzing the transcriptional profiles of this brain region in a neuron
subtype-specific manner, using a clinically relevant intravenous cocaine self-administration (IVSA)
mouse model. Furthermore, cell type-specific profiling/manipulation approaches will be used to
understand the function and mechanism of specific neuron subtypes during addictive process. To
achieve this goal, we have the following specific aims:
1) Profile cell type-specific transcriptome of different neuron subtypes of NAc using a mouse model of
cocaine IVSA;
2) The function and circuitry mechanisms of Tac2+ D1 MSN subtype in cocaine addiction;
3) Understand the epigenetic mechanism of the neuron subtype-specific functions in cocaine
addiction.
Completion of the proposed study will not only advance our understanding on how different NAc
neuron subtypes contribute to drug addiction, but also reveal novel therapeutic targets for treating this
disorder.
了解NAc在可卡因成瘾中的神经元亚型特异性功能
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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- 批准号:
10521971 - 财政年份:2022
- 资助金额:
$ 76.94万 - 项目类别:
A Wireless, Multimodal Neural Probe for Simultaneous Membrane-Free Neurochemical Sampling and Neuropharmacology
用于同步无膜神经化学采样和神经药理学的无线多模态神经探针
- 批准号:
10646362 - 财政年份:2022
- 资助金额:
$ 76.94万 - 项目类别:
Understanding neuronal subtype-specific function of NAc in cocaine addiction
了解 NAc 在可卡因成瘾中的神经元亚型特异性功能
- 批准号:
10381647 - 财政年份:2021
- 资助金额:
$ 76.94万 - 项目类别:
Understanding neuronal subtype-specific function of NAc in cocaine addiction
了解 NAc 在可卡因成瘾中的神经元亚型特异性功能
- 批准号:
10569638 - 财政年份:2021
- 资助金额:
$ 76.94万 - 项目类别:
A Wireless, Closed-Loop Neural Probe for Optogenetics, Pharmacology and Neurochemical Monitoring
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- 资助金额:
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Role of DNA Methylation in Cocaine Addiction
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10113569 - 财政年份:2017
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