Engineering Drosophila that self-administer cocaine
工程果蝇自我管理可卡因
基本信息
- 批准号:9439365
- 负责人:
- 金额:$ 20.31万
- 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:2017-02-13 至 2019-06-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAffectAmericanAnimal ModelBehavioralBiological AssayBiological ModelsCRISPR/Cas technologyCandidate Disease GeneChemicalsChemosensitizationChronicClustered Regularly Interspaced Short Palindromic RepeatsCocaineCocaine AbuseConsumptionDataDesire for foodDevelopmentDiseaseDopamineDoseDrosophila genusDrosophila melanogasterEconomic BurdenEngineeringEthanolFaceFoodFutureGenesGeneticGenetic ModelsGoalsHeritabilityHumanIllicit DrugsInsectaInsecticidesInvestigationKnowledgeMediatingMolecularPathway interactionsPharmaceutical PreparationsPhenotypePhysiologicalPhysiological ProcessesPlantsProcessPsychological reinforcementPublishingRegulationRewardsSelf AdministrationSelf-AdministeredSignal TransductionSubstance abuse problemSurveysTechnologyTestingTherapeuticTherapeutic InterventionTransgenic OrganismsUnited States Substance Abuse and Mental Health Services Administrationaddictionadverse outcomealcohol behavioralcohol responsebasebehavioral studycocaine usedesigndopamine transporterdopaminergic neurondrinkingexperimental studyfeedingflygenetic approachgenome wide association studyillicit drug usein vivonovelpreferencepsychostimulantreinforced behaviorresponsesuccessvinegar fly
项目摘要
–––– PROJECT SUMMARY / ABSTRACT –––––––––––––––––––––––––––––––––––––––––––––––––––––––
Millions of Americans abuse illicit drugs, including the stimulant cocaine. The annual economic burden this
creates is in the hundreds of billions of dollars. There is a substantial genetic contribution to the development
of substance abuse disorders (SUD), but many molecular pathways remain to be elucidated. The vinegar fly,
Drosophila melanogaster, has been a genetic model organism for more than a hundred years. Major strides
have been made in the last 10 years studying the behavioral responses to alcohol in flies, both in
characterizing novel conserved genes and pathways, but also in the development of new assays that resemble
addiction more closely. The goal of this proposal is to engineer Drosophila flies to self-administer cocaine. This
compound normally acts as an aversive antiherbivore chemical, and we hypothesize that this is because
cocaine amplifies dopaminergic signaling, which in flies is mainly, but not exclusively, aversive. First, we will
determine whether flies self-administer cocaine. We will establish dose response curves, and test the effects of
cocaine pre-exposure on cocaine preference/aversion. We will also test the impact of dopamine signaling on
cocaine consumption. Second, we will engineer flies that contain cocaine-sensitive dopamine transporters only
in these dopamine neurons required for the development of self-administration. In the other, aversive
dopamine neurons, these engineered flies will contain a cocaine-insensitive dopamine transporter. The
proposed experiments will yield a novel cocaine self-administration assay in a model organism that has
historically demonstrated great economy of scale and success in elucidating the molecular mechanisms of
numerous basic physiological, and behavioral processes.
- 项目概要/摘要-
数以百万计的美国人滥用非法药物,包括兴奋剂可卡因。每年的经济负担
创造了数千亿美元。基因对这种疾病的发展有很大的影响
药物滥用障碍(SUD),但许多分子途径仍有待阐明。醋蝇,
黑腹果蝇(Drosophila melanogaster)作为遗传模式生物已有一百多年的历史。重大进展
在过去的10年里,研究了苍蝇对酒精的行为反应,
表征新的保守基因和途径,而且在开发新的检测方法,
更紧密地上瘾。这项计划的目标是设计果蝇自我服用可卡因。这
化合物通常作为一种令人厌恶的抗草食动物化学物质,我们假设这是因为
可卡因放大多巴胺能信号,这在苍蝇中主要是,但不完全是,令人厌恶的。一是
确定苍蝇是否会自行吸食可卡因。我们将建立剂量反应曲线,并测试
可卡因预暴露对可卡因偏好/厌恶的影响。我们还将测试多巴胺信号对
可卡因消费第二,我们将设计只含有可卡因敏感多巴胺转运蛋白的果蝇,
在这些多巴胺神经元的发展所需的自我管理。另一方面,厌恶
多巴胺神经元,这些工程苍蝇将含有可卡因不敏感的多巴胺转运蛋白。的
提出的实验将在具有以下特征的模式生物中产生新的可卡因自我施用测定:
历史上证明了巨大的规模经济和成功阐明的分子机制,
许多基本的生理和行为过程。
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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Adrian Rothenfluh其他文献
Adrian Rothenfluh的其他文献
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{{ truncateString('Adrian Rothenfluh', 18)}}的其他基金
Transcriptional Regulation of Alcohol Sensitivity and Tolerance
酒精敏感性和耐受性的转录调控
- 批准号:
10651398 - 财政年份:2023
- 资助金额:
$ 20.31万 - 项目类别:
Control of Alcohol Responses by Actin-Regulating Genes
肌动蛋白调节基因控制酒精反应
- 批准号:
10889349 - 财政年份:2021
- 资助金额:
$ 20.31万 - 项目类别:
Control of Alcohol Responses by Actin-Regulating Genes
肌动蛋白调节基因控制酒精反应
- 批准号:
10471924 - 财政年份:2021
- 资助金额:
$ 20.31万 - 项目类别:
Control of Alcohol Responses by Actin-Regulating Genes
肌动蛋白调节基因控制酒精反应
- 批准号:
10683122 - 财政年份:2021
- 资助金额:
$ 20.31万 - 项目类别:
Control of Alcohol Responses by Actin-Regulating Genes
肌动蛋白调节基因控制酒精反应
- 批准号:
10738062 - 财政年份:2021
- 资助金额:
$ 20.31万 - 项目类别:
Control of Alcohol Responses by Actin-Regulating Genes
肌动蛋白调节基因控制酒精反应
- 批准号:
10306135 - 财政年份:2021
- 资助金额:
$ 20.31万 - 项目类别:
ATAC-ing dopaminergic cell identity with single-cell resolution
ATAC-ing 多巴胺能细胞识别与单细胞分辨率
- 批准号:
9980840 - 财政年份:2019
- 资助金额:
$ 20.31万 - 项目类别:
Mechanisms of alcohol-induced plasticitey mediated by Arf6
Arf6介导的酒精诱导可塑性机制
- 批准号:
10165421 - 财政年份:2018
- 资助金额:
$ 20.31万 - 项目类别:
Mechanisms of alcohol-induced plasticitey mediated by Arf6
Arf6介导的酒精诱导可塑性机制
- 批准号:
10414927 - 财政年份:2018
- 资助金额:
$ 20.31万 - 项目类别:
Mechanisms of alcohol-induced plasticitey mediated by Arf6
Arf6介导的酒精诱导可塑性机制
- 批准号:
9761413 - 财政年份:2018
- 资助金额:
$ 20.31万 - 项目类别:
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