Neuronal exosomes in cocaine abuse and treatment response in socially housed monkeys
社会饲养的猴子可卡因滥用和治疗反应中的神经元外泌体
基本信息
- 批准号:10393515
- 负责人:
- 金额:$ 38.75万
- 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:2019-07-01 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:AbstinenceAlcohol abuseBioinformaticsBiologicalBiological MarkersBiologyBiometryBloodBrainCaliberCellsCerebrospinal FluidCessation of lifeChronicClinicalCocaineCocaine AbuseCocaine use disorderDataDopamineDopamine ReceptorDrug abuseFailureFemaleFundingFutureGoalsHeroin AbuseIndividualIndividual DifferencesIntravenousLaboratoriesLipidsLiquid substanceMacaca fascicularisMeasuresMetabolicModelingMolecularMolecular ProfilingMonkeysNational Institute of Drug AbuseNeuronsOrganismParentsPathologicPharmaceutical PreparationsPharmacologyPhysiologicalPlasmaPositron-Emission TomographyPredispositionPreventivePrognostic MarkerProteinsPsychological reinforcementPublic HealthRNARelapseResearch PersonnelResearch ProposalsSalivaSame-sexSamplingSex DifferencesSocial HierarchySocial ProblemsStressSymptomsTestingTimeTreatment EfficacyTreatment outcomeUnited StatesWorkbasebehavior testcell typecocaine self-administrationcocaine usecognitive testingcostcost effectivediagnostic biomarkerdifferential expressionefficacy testingexosomemalemethamphetamine abusemolecular markermultidisciplinarymultiple omicsnano-exosomesnanovesiclenervous system disorderneuroimagingnonhuman primatenovelpersonalized medicinereceptorreceptor functionsexsocialsocial groupsuccesstargeted treatmenttooltreatment responsevesicular release
项目摘要
Project Summary/Abstract
Cocaine use disorder (CUD) continues to be a major public health and social problem in the United States. A
hallmark of CUD is individual differences in vulnerability, relapse and treatment efficacy. Our overall goal is to
achieve a better understanding of individual differences in the long-term consequences of the reinforcing
effects of cocaine using a unique nonhuman primate model of CUD. We propose to use neuronal-derived
exosomes (NDE) in the blood to identify molecular biomarkers associated with an individual's vulnerability to
cocaine abuse, susceptibility to relapse following abstinence, and success or failure of targeted therapies for
cocaine abuse. Exosomes are nano-vesicles that are released by all cell types. Those released by cells under
stressed or pathologic states are different from those released under normal physiologic conditions. Taking
advantage of this difference, several exosome-based diagnostic and prognostic biomarkers have been
successfully developed. Recent studies have also shown that exosomes in biofluids can be used to establish
molecular signatures associated with methamphetamine, heroin, and alcohol abuse. However, exosomes have
not been used to understand cocaine abuse – the focus of this application. The proposed study capitalizes on
a timely opportunity to use plasma samples from an ongoing NIDA-funded study (R01 DA017763-11; PI:
Nader) to understand cocaine abuse in socially housed female and male monkeys. The parent study is testing
the efficacy of several pharmacological agents thought to work differently in dominant and subordinate female
and male monkeys. All monkeys (socially housed and naturally forming dominant and subordinate hierarchies)
are undergoing comprehensive behavioral and cognitive testing, and neuroimaging of central dopamine D2/D3
receptor (D2/D3R) availability using positron emission tomography (PET) imaging. With the costs of key
measures covered by existing funding, the availability of plasma samples from these monkeys offers a
valuable and cost-effective opportunity to advance our understanding of how exosomes could provide a non-
invasive molecular tool to inform us about cocaine abuse and treatment outcomes. Pilot and feasibility data (a)
validate our ability to isolate and characterize NDEs from stored plasma samples, and (b) support the utility of
NDE biomarkers to understand the molecular effects of cocaine self-administration (SA), and effects of social
ranking on cocaine vulnerability and treatment outcomes in male and female monkeys. Thus, we propose two
Specific Aims: I. To characterize NDEs associated with cocaine SA in socially housed male and female
monkeys. II. To characterize NDEs associated with success or failure of pharmacological agents to decrease
cocaine SA in socially housed male and female monkeys. Our results will significantly advance progress
toward characterization of non-invasive biomarkers for molecular understanding of cocaine abuse vulnerability
and relapse, and contribute in developing a personalized-medicine strategy for treating drug abuse.
项目总结/文摘
项目成果
期刊论文数量(0)
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Neuronal exosomes in cocaine abuse and treatment response in socially housed monkeys
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