Dopamine Neuronal Microcircuits Controlling Methamphetamine Seeking Behavior
多巴胺神经元微电路控制甲基苯丙胺寻求行为
基本信息
- 批准号:10591238
- 负责人:
- 金额:$ 14.97万
- 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:2021-07-19 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAnatomyApplications GrantsBehaviorBioinformaticsBrainCellsCharacteristicsChicagoChronicCollaborationsDataDopamineDrug AddictionDrug ModelingsDrug abuseEducational ModelsEnvironmentFacultyGeneticGenetic TranscriptionGlutathioneGrantKnowledgeLabelLaboratoriesMarylandMentorsMentorshipMetabolicMethamphetamineMethamphetamine dependenceMethodologyMitochondriaMolecularMolecular BiologyMoraleMusNational Institute of Drug AbuseNeurobiologyNeuronsOxidative StressOxygen ConsumptionPopulationPreparationPropertyQuality of lifeResearchResearch ActivityResearch PersonnelResearch ProposalsResistanceRoleScientistSecureSelf AdministrationSystemTechnologyTherapeuticTimeTrainingTraining ActivityUnderrepresented PopulationsUniversitiesVentral Tegmental AreaViralWorkWritingaddictionbrain researchdopaminergic neurondrug seeking behaviorexperiencefightingimmunocytochemistrymedical schoolsmembermethamphetamine exposuremitochondrial metabolismmotivated behaviormouse modelneuronal circuitryneurotransmissionnovelnovel therapeuticsoxidative damageprogramsskillstranscriptomics
项目摘要
Project Summary/Abstract
This proposal is submitted to support the transition of Dr. Dominguez-Lopez from a mentored trainee to an
independent investigator in the neurobiology of drug addiction, specifically studying the dopamine
microcircuits controlling drug-seeking behavior. Dr. Dominguez-Lopez will work under the mentorship of Dr.
Mary Kay Lobo at the University of Maryland School of Medicine (UMSOM), investigating the role of dopamine
neurotransmission in the ventral tegmental area (VTA) in methamphetamine (METH) self-administration
behavior. Dr. Lobo is a recognized expert in motivated behavior and dopamine neurotransmission in the
context of drug abuse. Dr. Lobo’s laboratory combines mouse models of drug self-administration with
mitochondrial metabolism, molecular biology, genetics, and immunocytochemistry, providing a dynamic
environment for Dr. Dominguez-Lopez to become an experienced scientist. The submitted proposal
incorporates scientific training in methodologies to study mitochondrial metabolism, transcriptional analysis,
bioinformatics, and genetic labeling of active neuronal populations. The applicant will be receiving training in
educational methods, scientific writing, grant preparation, and other skills necessary to become an
independent brain research scientist from an underrepresented group. The proposed program includes
mentoring interactions with Drs. Joseph Cheer, Seth Ament, Brian Polster, faculty members of UMSOM, and
Dr. Marisela Morales from NIDA IRP. In addition, Dr. Rajeshwar Awatramani from Northwestern University in
Chicago will be a consultant in this project. The short-term objective of this proposal is to enhance Dr.
Dominguez-Lopez’s knowledge of mitochondrial metabolism and single-cell transcriptomics applied to
dopaminergic circuits. In the long-term, this will enable Dr. Dominguez-Lopez to secure protected time for
training and research activities, establish new collaborations, and pursue his novel independent research
resulting in competitive grant proposals. Data obtained by Dr. Dominguez-Lopez indicates that prolonged
METH self-administration in mice produces a decrease of dopamine neurons in the VTA, decreases dopamine
cell excitability, increases mitochondrial oxygen consumption rate, and decreases levels of glutathione. These
observations are concurrent with increased drug-seeking behavior. This research proposal expands on those
findings to identify metabolic and molecular characteristics in dopamine circuits that provide resistance or
vulnerability to METH exposure. The central hypothesis is that a subpopulation of VTA dopamine neurons is
responsible for METH-seeking behavior, forming a microcircuit resistant to mitochondrial oxidative stress
induced by chronic METH exposure. The proposed aims are 1) Identifying VTA dopamine microcircuits
encoding METH-seeking behavior and 2) Metabolic characteristics of VTA dopamine neurons encoding
METH-seeking behavior. Identifying the specific brain circuits responsible for METH addictive properties is a
first step to developing therapeutic strategies to help addicts recover from METH addiction.
项目总结/摘要
提交该提案是为了支持多明格斯-洛佩兹博士从一名接受指导的受训人员过渡到一名
药物成瘾神经生物学的独立研究者,特别是研究多巴胺
控制寻药行为的微电路多明格斯-洛佩兹博士将在博士的指导下工作。
马里兰州大学医学院的玛丽凯·洛博(Mary Lobo)研究了多巴胺的作用
甲基苯丙胺(METH)自我给药时腹侧被盖区(VTA)的神经传递
行为Lobo博士是一位公认的动机行为和多巴胺神经传递专家,
药物滥用的背景。Lobo博士的实验室将自我给药的小鼠模型与
线粒体代谢,分子生物学,遗传学和免疫细胞化学,提供了一个动态的
多明格斯-洛佩兹博士成为一名经验丰富的科学家的环境。的议案
结合了研究线粒体代谢,转录分析,
生物信息学和活性神经元群体的遗传标记。申请人将接受以下培训:
教育方法,科学写作,拨款准备和其他必要的技能,成为一个
一个来自弱势群体的独立大脑研究科学家。拟议方案包括
与约瑟夫·谢尔博士,塞思·阿门特,布赖恩·波尔斯特,UMSOM的教职员工,
博士NIDA IRP的Marisela Morales此外,西北大学的Rajeshwar Awatramani博士
芝加哥将是这个项目的顾问。该建议的短期目标是提高博士。
Dominguez-Lopez的线粒体代谢和单细胞转录组学知识适用于
多巴胺能回路。从长远来看,这将使多明格斯-洛佩兹博士能够获得受保护的时间,
培训和研究活动,建立新的合作,并追求他的新颖的独立研究
从而产生竞争性的赠款提案。多明格斯-洛佩兹博士获得的数据表明,
在小鼠中METH自我给药产生腹侧被盖区中多巴胺神经元的减少,
细胞兴奋性,增加线粒体耗氧率,并降低谷胱甘肽水平。这些
观察结果与增加的药物寻求行为同时发生。这项研究计划扩展了这些
研究结果,以确定多巴胺回路中的代谢和分子特征,
暴露于甲基苯丙胺的脆弱性。中心假设是腹侧被盖区多巴胺神经元的亚群是
负责寻找甲基苯丙胺的行为,形成抵抗线粒体氧化应激的微电路
是由长期接触甲基苯丙胺引起的提出的目标是1)识别VTA多巴胺微电路
2)腹侧被盖区多巴胺神经元编码的代谢特征
寻求冰毒的行为确定负责METH成瘾特性的特定大脑回路是一个重要的问题。
第一步,制定治疗策略,以帮助成瘾者从METH成瘾中恢复。
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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Sergio Dominguez Lopez其他文献
Sergio Dominguez Lopez的其他文献
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{{ truncateString('Sergio Dominguez Lopez', 18)}}的其他基金
Dopamine Neuronal Microcircuits Controlling Methamphetamine Seeking Behavior
多巴胺神经元微电路控制甲基苯丙胺寻求行为
- 批准号:
10440637 - 财政年份:2021
- 资助金额:
$ 14.97万 - 项目类别:
Dopamine neuronal microcircuits controlling methamphetamine seeking behavior
多巴胺神经元微电路控制甲基苯丙胺寻求行为
- 批准号:
9977578 - 财政年份:2020
- 资助金额:
$ 14.97万 - 项目类别:
Dopamine neuronal microcircuits controlling methamphetamine seeking behavior
多巴胺神经元微电路控制甲基苯丙胺寻求行为
- 批准号:
10152578 - 财政年份:2020
- 资助金额:
$ 14.97万 - 项目类别:
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