Brain and Behavioral Effects of PENK Gene Manipulation in Rat Nucleus Accumbens
PENK 基因操作对大鼠伏隔核的大脑和行为影响
基本信息
- 批准号:8051553
- 负责人:
- 金额:$ 4.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-04-01 至 2013-03-31
- 项目状态:已结题
- 来源:
- 关键词:16 year oldAcuteAdolescenceAdolescentAdultAlcohol or Other Drugs useAreaBehaviorBehavioralBiologyBrainCalculiCannabinoidsCannabisCannabis sativa plantChronicDataDeltastabDevelopmentDiseaseDopamineDown-RegulationDrug AddictionDrug abuseEarly treatmentEmotionsEnkephalinsEpidemiologic StudiesEpidemiologyExposure toFutureGene ExpressionGene TransferGenesGeneticGoalsHeroinIllicit DrugsIntakeKnowledgeLaboratoriesLearningLinkLiteratureMarijuanaMarijuana SmokingMediatingMental disordersMicrodialysisMolecularMorphineMotivationNeurobiologyNeurotransmittersNucleus AccumbensOpiatesOpioidOpioid PeptidePharmaceutical PreparationsPredispositionPreventionPublic HealthRNA InterferenceRattusReceptor GeneReportingRewardsRisk FactorsSelf AdministrationSocietiesStructureSubstance abuse problemSystemTeenagersTestingTetrahydrocannabinolTransfer RNAUp-RegulationVirusWorkanimal datadrug of abuseearly onsetendogenous cannabinoid systemendogenous opioidsgenetic manipulationhedonicin vivoinsightinterestneural circuitneurochemistryneurodevelopmentoverexpressionpreproenkephalinrelating to nervous systemresponsesocialsubstance abuse treatmenttool
项目摘要
DESCRIPTION (provided by applicant): Marijuana is the illicit drug most frequently used by teenagers, and exposure to cannabis normally predates the use of "heavy" drugs and psychiatric disorders. Such data appear to support the controversial "gateway" hypothesis of cannabis as a stepping stone towards abuse of other drugs. Despite strong epidemiological evidence of an association between cannabis use during adolescence and later drug abuse, few one-to-one neurobiological correlations between early cannabis use and subsequent drug abuse vulnerability exist. Reproducible animal data has shown that cannabis exposure during adolescence potentiated adult heroin self-administration behavior and caused discrete alterations of preproenkephalin (PENK), a gene important for reward and hedonic state, in the nucleus accumbens (Acb), a limbic-related brain area central to reward. The proposed work will directly test whether there is a causal link between PENK disturbance seen with early-onset cannabis use and progression to the use of other illicit drugs. Virus-mediated gene transfer (PENK overexpression) and RNA interference (PENK knockdown) will be used as genetic approaches to study the behavioral and neurochemical states associated with drug abuse. Specific Aim 1 will determine whether direct manipulation of the PENK gene in the Acb shell alters heroin self-administration behavior. Disturbances of neurotransmitters in brain areas linked to reward will be identified by studying whether genetic manipulation of PENK alters opiate-induced dopamine levels in the Acb shell using in vivo microdialysis (Specific Aim 2). To characterize specific molecular alterations that could underlie behavioral and neurochemical differences observed in association with genetic manipulation of PENK, brains will be analyzed for expression of genes and receptors linked to the opioid, DAergic, and cannabinoid neural systems (Specific Aim 3). Substance abuse is a major public health issue, and understanding risk factors predisposing to drug abuse disorders will be crucial to the prevention and treatment of these illnesses. Altogether, this project will provide insight as to whether there exists a long-term impact of cannabis exposure during development to substantiate a neurobiological "gateway" hypothesis and, if so, help to identify potential risk factors in adolescence that influence the vulnerability for drug abuse in adulthood.
描述(由申请人提供):大麻是青少年最常使用的非法药物,接触大麻通常早于使用“重度”药物和精神疾病。这些数据似乎支持了有争议的“门户”假说,即大麻是滥用其他药物的垫脚石。尽管有强有力的流行病学证据表明青春期大麻使用与后来的药物滥用之间存在关联,但早期大麻使用与随后的药物滥用脆弱性之间几乎不存在一对一的神经生物学相关性。可重复的动物数据表明,青春期接触大麻会增强成人海洛因的自我给药行为,并导致伏隔核(Acb)(与边缘系统相关的大脑区域)中前脑啡肽原(PENK)的离散改变,PENK是一种对奖赏和享乐状态很重要的基因。以奖励为中心。拟议的工作将直接测试早发性大麻使用引起的 PENK 紊乱与其他非法药物使用进展之间是否存在因果关系。病毒介导的基因转移(PENK 过度表达)和 RNA 干扰(PENK 敲低)将用作研究与药物滥用相关的行为和神经化学状态的遗传方法。具体目标 1 将确定直接操作 Acb 外壳中的 PENK 基因是否会改变海洛因自我给药行为。通过使用体内微透析研究 PENK 的基因操作是否会改变阿片类药物诱导的 Acb 壳中的多巴胺水平,可以确定与奖励相关的大脑区域中神经递质的干扰(具体目标 2)。为了表征与 PENK 基因操作相关的行为和神经化学差异背后可能存在的特定分子改变,将分析大脑中与阿片类、DAergic 和大麻素神经系统相关的基因和受体的表达(具体目标 3)。药物滥用是一个重大的公共卫生问题,了解易患药物滥用疾病的危险因素对于预防和治疗这些疾病至关重要。总而言之,该项目将深入了解在发育过程中接触大麻是否存在长期影响,以证实神经生物学“门户”假设,如果是这样,则有助于确定青春期影响药物滥用脆弱性的潜在风险因素成年后。
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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Hilarie C Tomasiewicz其他文献
Hilarie C Tomasiewicz的其他文献
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{{ truncateString('Hilarie C Tomasiewicz', 18)}}的其他基金
Brain and Behavioral Effects of PENK Gene Manipulation in Rat Nucleus Accumbens
PENK 基因操作对大鼠伏隔核的大脑和行为影响
- 批准号:
7485913 - 财政年份:2008
- 资助金额:
$ 4.64万 - 项目类别:
Brain and Behavioral Effects of PENK Gene Manipulation in Rat Nucleus Accumbens
PENK 基因操作对大鼠伏隔核的大脑和行为影响
- 批准号:
8246491 - 财政年份:2008
- 资助金额:
$ 4.64万 - 项目类别:
Brain and Behavioral Effects of PENK Gene Manipulation in Rat Nucleus Accumbens
PENK 基因操作对大鼠伏隔核的大脑和行为影响
- 批准号:
7620396 - 财政年份:2008
- 资助金额:
$ 4.64万 - 项目类别:
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