Cocaine-induced neuroplasticity: a new role for TGF beta signaling
可卡因诱导的神经可塑性:TGFβ信号传导的新作用
基本信息
- 批准号:9278142
- 负责人:
- 金额:$ 44.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-06-01 至 2019-05-31
- 项目状态:已结题
- 来源:
- 关键词:ActinsActivin ReceptorActivinsAddressAnimalsBehaviorBehavioralBrainCell NucleusChronicCocaineCocaine AbuseCocaine DependenceComplexCuesDataDendritic SpinesDevelopmentDiseaseDopamineDrug AddictionEventGene TargetingGenetic TranscriptionGoalsGuanosine Triphosphate PhosphohydrolasesHumanLeadLightMADH3 geneMaintenanceMapsMeasuresMediatingMissionMolecularMorphologyNeuronal PlasticityNeuronsNucleus AccumbensPathway interactionsPharmaceutical PreparationsPharmacotherapyProteinsPsychostimulant dependencePublic HealthReceptor ActivationReceptor SignalingRegulationRelapseReportingResearchRewardsRodentRoleSelf AdministrationSelf-AdministeredSignal PathwaySignal TransductionStructureTestingTherapeutic AgentsTimeTranscriptional RegulationTransforming Growth Factor betaUnited States National Institutes of HealthWithdrawalWorkaddictionalpha Actinbasebehavioral plasticitycocaine exposurecombatcravingdrug cravingdrug of abusedrug seeking behavioreffective therapyexperimental studyextracellularknock-downmemberneuroadaptationneuromechanismnovelnovel therapeuticsoverexpressionpsychostimulantpublic health relevancereceptor expressionrelating to nervous systemsuccesstranscription factor
项目摘要
DESCRIPTION (provided by applicant): The proposed studies investigate the role of activin receptor signaling cascades in mediating the long-lasting changes in the brain's reward circuits, which contribute to the complex behavioral abnormalities that comprise an addicted state. To date there is no effective pharmacotherapy for addiction to stimulants, such as cocaine, highlighting the dire need for further understanding of how such drugs of abuse "re-wire" the brain. Neuronal plasticity is considered a neural substrate of the long-term addicted state, but there is a scarcity of mechanistic evidence that explores the molecular mechanism of cocaine-induced structural plasticity. Guided by exciting preliminary data demonstrating that in the Nucleus Accumbens (NAc) of animals of self-administering cocaine, activin receptor expression and signaling is increased, this application will test the following hypotheses: (Aim I) cocaine self-administration regulates the activin receptor-Smad pathway. Consequently, following cocaine self-administration the activin-smad pathway regulates both (a) actin dynamics and (b) Smad gene targets; (Aim II) Activin-Smad pathways are key molecular mechanisms underlying cocaine-induced dendritic spine plasticity of NAc neurons following cocaine self-administration; (Aim III) Activin receptor and Smad signaling pathways directly mediate cocaine seeking and craving as measured by reinstatement behaviors. This application presents an opportunity to determine, for the first time, the causal role for TGFBeta/activin-smad signaling cascades in facilitating drug seeking behaviors by examining cocaine-induced plasticity on cellular (i.e. structural) and behavioral levels (i.e. reinstatement). The findings from the work in this application will elucidate mechanisms by which chronic cocaine exposure induces long-term changes in plasticity of NAc neurons, and provides new directions for the development of novel therapies for cocaine addiction.
描述(由申请人提供):拟议的研究调查了激活素受体信号级联在调节大脑奖励回路的长期变化中的作用,这些变化导致了构成成瘾状态的复杂行为异常。迄今为止,还没有有效的药物疗法来治疗可卡因等兴奋剂成瘾,这凸显了迫切需要进一步了解此类滥用药物如何“重新连接”大脑。神经元可塑性被认为是长期成瘾状态的神经基础,但缺乏探索可卡因诱导的结构可塑性分子机制的机制证据。令人兴奋的初步数据表明,在自我施用可卡因的动物的伏核 (NAc) 中,激活素受体表达和信号传导增加,本申请将测试以下假设:(目标 I)可卡因自我施用调节激活素受体-Smad途径。因此,在自我施用可卡因后,激活素-smad 通路既调节 (a) 肌动蛋白动态又调节 (b) Smad 基因靶标; (目标 II)Activin-Smad 通路是可卡因自我给药后可卡因诱导 NAc 神经元树突棘可塑性的关键分子机制; (目标 III)激活素受体和 Smad 信号通路直接介导可卡因寻求和渴望(通过恢复行为测量)。该应用通过检查可卡因诱导的细胞(即结构)和行为水平(即恢复)可塑性,首次确定 TGFBeta/activin-smad 信号级联在促进药物寻求行为中的因果作用。本申请的工作结果将阐明长期接触可卡因导致 NAc 神经元可塑性长期变化的机制,并为可卡因成瘾新疗法的开发提供新方向。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
DAVID M DIETZ其他文献
DAVID M DIETZ的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('DAVID M DIETZ', 18)}}的其他基金
Contributions of aberrant synaptic protein monoaminylation to opiate use disorder
异常突触蛋白单胺化对阿片类药物使用障碍的影响
- 批准号:
10501338 - 财政年份:2022
- 资助金额:
$ 44.27万 - 项目类别:
Contributions of aberrant synaptic protein monoaminylation to opiate use disorder
异常突触蛋白单胺化对阿片类药物使用障碍的影响
- 批准号:
10681305 - 财政年份:2022
- 资助金额:
$ 44.27万 - 项目类别:
Heroin-induced plasticity: the role of actin dynamics
海洛因诱导的可塑性:肌动蛋白动力学的作用
- 批准号:
9899969 - 财政年份:2019
- 资助金额:
$ 44.27万 - 项目类别:
Neuron Subtype Translatomics in Opiate Abuse
阿片类药物滥用中的神经元亚型翻译组学
- 批准号:
10013157 - 财政年份:2019
- 资助金额:
$ 44.27万 - 项目类别:
Heroin-induced plasticity: the role of actin dynamics
海洛因诱导的可塑性:肌动蛋白动力学的作用
- 批准号:
10551185 - 财政年份:2019
- 资助金额:
$ 44.27万 - 项目类别:
Cocaine-induced neuroplasticity: a new role for TGF beta signaling
可卡因诱导的神经可塑性:TGFβ信号传导的新作用
- 批准号:
8670960 - 财政年份:2014
- 资助金额:
$ 44.27万 - 项目类别:
Cocaine-induced neuroplasticity: a new role for TGF beta signaling
可卡因诱导的神经可塑性:TGFβ信号传导的新作用
- 批准号:
9058018 - 财政年份:2014
- 资助金额:
$ 44.27万 - 项目类别:
Cocaine-induced neuroplasticity: a new role for TGF beta signaling
可卡因诱导的神经可塑性:TGFβ信号传导的新作用
- 批准号:
8853842 - 财政年份:2014
- 资助金额:
$ 44.27万 - 项目类别:
Individual Differences in Sensitization to Amphetamine
对安非他明敏感度的个体差异
- 批准号:
7207996 - 财政年份:2006
- 资助金额:
$ 44.27万 - 项目类别:
Individual Differences in Sensitization to Amphetamine
对安非他明敏感度的个体差异
- 批准号:
7056950 - 财政年份:2006
- 资助金额:
$ 44.27万 - 项目类别:
相似国自然基金
胰岛素受体胞内激酶活性结构域“激活”/“抑制”构象的解析及功能调节机制
- 批准号:32371227
- 批准年份:2023
- 资助金额:50 万元
- 项目类别:面上项目
电针激活大麻素CB1受体抑制mPFC–LS环路缓解应激性焦虑的机制
- 批准号:82374584
- 批准年份:2023
- 资助金额:48 万元
- 项目类别:面上项目
非受体酪氨酸磷酸酶在湍流介导的整合素α5-YAP通路活化以及内皮激活中的作用与机制研究
- 批准号:82330012
- 批准年份:2023
- 资助金额:220 万元
- 项目类别:重点项目
α2A/2B-肾上腺素受体偏向激活Gαs的激动剂作用位点及其功能相关性研究
- 批准号:
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
生长抑素受体SSTR3与配体识别及激活的机制研究
- 批准号:
- 批准年份:2022
- 资助金额:30 万元
- 项目类别:青年科学基金项目
相似海外基金
Cocaine-induced neuroplasticity: a new role for TGF beta signaling
可卡因诱导的神经可塑性:TGFβ信号传导的新作用
- 批准号:
8670960 - 财政年份:2014
- 资助金额:
$ 44.27万 - 项目类别:
Cocaine-induced neuroplasticity: a new role for TGF beta signaling
可卡因诱导的神经可塑性:TGFβ信号传导的新作用
- 批准号:
9058018 - 财政年份:2014
- 资助金额:
$ 44.27万 - 项目类别:
Cocaine-induced neuroplasticity: a new role for TGF beta signaling
可卡因诱导的神经可塑性:TGFβ信号传导的新作用
- 批准号:
8853842 - 财政年份:2014
- 资助金额:
$ 44.27万 - 项目类别: