Dissecting the role of granulocyte-colony stimulating factor in cocaine-mediated behavioral plasticity
剖析粒细胞集落刺激因子在可卡因介导的行为可塑性中的作用
基本信息
- 批准号:9492785
- 负责人:
- 金额:$ 18.84万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-07-01 至 2022-06-30
- 项目状态:已结题
- 来源:
- 关键词:AbstinenceAdaptive Immune SystemAffectAnimalsAttenuatedAwardBehaviorBehavioralBrainCocaineCocaine AbuseColony-Stimulating Factor ReceptorsCuesDRD2 geneDataData SetDevelopmentDiseaseDoseEconomicsEnterobacteria phage P1 Cre recombinaseExposure toExtinction (Psychology)FDA approvedFOS geneFamilyFunctional disorderGene ExpressionGenesGoalsGranulocyte Colony-Stimulating FactorGranulocyte Colony-Stimulating Factor ReceptorsGrowth FactorImmuneImmune systemInfusion proceduresInjectionsInvestigationLeadLinkMeasuresMediatingMental disordersMentorsMentorshipMethodsMicroRNAsMolecularMorbidity - disease rateMotivationMusNeuroimmuneNeuronal PlasticityNeuronsNucleus AccumbensPathologicPathway AnalysisPathway interactionsPatientsPatternPeripheralPharmaceutical PreparationsPharmacotherapyPhasePlayPopulationProcessProductionPsychiatric therapeutic procedurePublic HealthRandomizedRattusRegulationRelapseReportingResearchResearch PersonnelRewardsRoleSalineSecond Messenger SystemsSelf AdministrationSelf-AdministeredSeriesSerumSignal PathwaySignal TransductionSocietiesTherapeuticTrainingTransgenic AnimalsTreatment FactorUp-RegulationViral GenesViral VectorYasminaddictionbasebehavioral plasticitybehavioral responsebrain reward regionscell typechemokinecocaine usecostcytokinedifferential expressioneffective therapyexperimental studyillicit drug useimmune functionimmune system functioninhibitor/antagonistinnate immune functioninsightknock-downmRNA sequencingmolecular targeted therapiesneuronal circuitrynovelpreferencepsychostimulantrelating to nervous systemresponsesocialstimulant abusetherapeutic targettranscriptome
项目摘要
Addiction to psychostimulants such as cocaine represents a major public health issue exacting tremendous
financial and social costs. Despite this, psychostimulant use disorder remains a recalcitrant condition with no
currently FDA-approved medications for its treatment. In many fields of psychiatric research, the link between
the brain and the immune system has been heavily studied as a way to determine pathophysiology and to find
new methods of treatment. While it is known that cocaine can alter the function of both the innate and adaptive
immune systems, the link between these immune changes and maladaptive drug taking and seeking behaviors
remains minimally explored. In a series of initial experiments, we examined how experimenter or self-
administered cocaine altered the serum profile of 32 cytokines. Of these, we found that granulocyte-colony
stimulating factor (G-CSF) was increased by cocaine, and the serum levels showed linear correlation with
behavioral response to cocaine. Behaviorally, injections of G-CSF alter the dose-response curve for cocaine
place preference, and facilitate extinction and reduce reinstatement of cocaine seeking. Taken together, these
preliminary studies demonstrate that G-CSF is a potent modulator of cocaine-induced behavioral plasticity, and
may be a potential therapeutic target for prolonging abstinence in cocaine use disorder. Under the mentorship
of Drs. Eric Nestler and Yasmin Hurd I will seek to further clarify the role of G-CSF in addiction while gaining
additional training to allow me to transition to independence. In Aim 1 of this proposal I will interrogate the
effects of G-CSF in the nucleus accumbens (NAc) in a cell-type specific manner by using viral vectors to knock
down the G-CSF receptor in populations of D1 and D2 positive medium spiny neurons prior to cocaine self-
administration, extinction and reinstatement. These experiments will provide insight into the microcircuitry
underlying the behavioral effect of G-CSF, and will provide me crucial training in self-administration and
targeted manipulation of gene expression. In Aim 2, I will seek to identify G-CSF responsive genes in NAc that
account for its behavioral effect. I will perform mRNA sequencing of the NAc from animals self-administering
cocaine, followed by differential expression and pathway analysis. The behavioral effect of highly regulated
genes and pathways will be interrogated by viral gene manipulation prior to cocaine self-administration,
extinction and reinstatement. These experiments will provide me with crucial mentoring in creation, analysis
and utilization of large sequencing datasets, while also providing detailed information as to how G-CSF affects
cocaine-related behavioral plasticity. In summary, the research proposed in this award will elucidate the neural
and molecular mechanisms of a translationally-relevant treatment target, while providing me with sufficient
mentorship to transition into an independent investigator.
可卡因等精神兴奋剂成瘾是一个严重的公共卫生问题
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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Drew Kiraly其他文献
Drew Kiraly的其他文献
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{{ truncateString('Drew Kiraly', 18)}}的其他基金
Targeting gut brain-signaling to reduce cocaine seeking behaviors
针对肠道大脑信号传导以减少可卡因寻求行为
- 批准号:
10733638 - 财政年份:2023
- 资助金额:
$ 18.84万 - 项目类别:
Targeting the host metabolome to reverse drug-induced epigenetic changes
靶向宿主代谢组以逆转药物诱导的表观遗传变化
- 批准号:
10881008 - 财政年份:2020
- 资助金额:
$ 18.84万 - 项目类别:
Targeting the host metabolome to reverse drug-induced epigenetic changes
靶向宿主代谢组以逆转药物诱导的表观遗传变化
- 批准号:
10044659 - 财政年份:2020
- 资助金额:
$ 18.84万 - 项目类别:
Targeting the host metabolome to reverse drug-induced epigenetic changes
靶向宿主代谢组以逆转药物诱导的表观遗传变化
- 批准号:
10205016 - 财政年份:2020
- 资助金额:
$ 18.84万 - 项目类别:
Targeting the host metabolome to reverse drug-induced epigenetic changes
靶向宿主代谢组以逆转药物诱导的表观遗传变化
- 批准号:
10666547 - 财政年份:2020
- 资助金额:
$ 18.84万 - 项目类别:
Targeting the host metabolome to reverse drug-induced epigenetic changes
靶向宿主代谢组以逆转药物诱导的表观遗传变化
- 批准号:
10408789 - 财政年份:2020
- 资助金额:
$ 18.84万 - 项目类别:
Neuroimmune modulation of neuronal function during cocaine conditioning
可卡因调理过程中神经元功能的神经免疫调节
- 批准号:
10015251 - 财政年份:2019
- 资助金额:
$ 18.84万 - 项目类别:
Dissecting the role of granulocyte-colony stimulating factor in cocaine-mediated behavioral plasticity
剖析粒细胞集落刺激因子在可卡因介导的行为可塑性中的作用
- 批准号:
9370396 - 财政年份:2017
- 资助金额:
$ 18.84万 - 项目类别:
Dissecting the role of granulocyte-colony stimulating factor in cocaine-mediated behavioral plasticity
剖析粒细胞集落刺激因子在可卡因介导的行为可塑性中的作用
- 批准号:
10190875 - 财政年份:2017
- 资助金额:
$ 18.84万 - 项目类别:
Kalirin-7 is essential in cocaine signaling: focus on nucleus accumbens
Kalirin-7 在可卡因信号传导中至关重要:关注伏隔核
- 批准号:
8352102 - 财政年份:2010
- 资助金额:
$ 18.84万 - 项目类别:
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