Circuit and epigenetic mechanisms underlying incubation of methamphetamine craving
甲基苯丙胺渴望潜藏的回路和表观遗传机制
基本信息
- 批准号:9751825
- 负责人:
- 金额:$ 24.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-01 至 2021-07-31
- 项目状态:已结题
- 来源:
- 关键词:AbstinenceAmygdaloid structureAreaBindingBioinformaticsBrainChIP-seqCholera Toxin Protomer BChromatinClustered Regularly Interspaced Short Palindromic RepeatsCocaineCorpus striatum structureCuesDataData AnalysesDevelopmentDopamineDorsalDrug AddictionDrug usageEnvironmentEnzymesEpigenetic ProcessExposure toFamilyFutureGene TargetingGenomicsGrantHDAC5 geneHeroinHumanIncubatedInstitutionKnock-outKnowledgeMediatingMentorsMentorshipMethamphetamineMethamphetamine dependenceMethodsModelingNeuronsPharmaceutical PreparationsPhasePlayPrefrontal CortexProtocols documentationRNARattusRecording of previous eventsRelapseResearch PersonnelResearch ProposalsRoleSelf AdministrationSubstantia nigra structureSystemTechniquesTechnologyTestingThalamic structureTracerTrainingTraining SupportTranscriptTranscriptional RegulationViralWithdrawalactivity markerbasebrain tissuecareercravingdesigner receptors exclusively activated by designer drugsdisorder later incidence preventiondrug cravingdrug relapsedrug withdrawalinsightmethamphetamine userneuromechanismnovelnovel strategiesnucleaseoverexpressionprofessorreceptortenure tracktherapeutic targettranscriptome sequencing
项目摘要
Cue-induced drug craving progressively increases after withdrawal, a phenomenon termed ‘incubation of
drug craving’. During the last decade, mechanistic studies have primarily focused on incubation of cocaine
craving. In contrast, very few studies have examined the mechanisms underlying incubation of
methamphetamine (Meth) craving. Here, I propose to study circuit and epigenetic mechanisms underlying
incubation of Meth craving with a focus on the dorsal striatum (DS) region. The choice of this brain area is based
on my preliminary data implicating a critical role of DS neuronal activity and a potential role of DS histone
deacetylase 5 (HDAC5, an epigenetic-related enzyme) in incubation of Meth craving. At the circuit level, I will
use a retrograde tracing technique (CTb, cholera toxin subunit B) in combination with the neuronal activity
marker Fos to identify critical afferent projections to the DS that are activated during incubation of Meth craving.
Next, I will use a novel retro-DREADD (Designer Receptors Exclusively Activated by Designer Drugs) method to
study the causal role of afferent projections to the DS in incubation of Meth craving. At the epigenetic level, I will
combine chromatin immunoprecipitation-sequencing (ChIP-seq) with RNA-sequencing (RNA-seq) to identify
downstream gene targets of HDAC5 in DS whose expression is altered after prolonged withdrawal (1 month)
from Meth self-administration. I will also use the CRISPR-Cas9 system to examine the causal role of DS HDAC5
in incubation of Meth craving. My proposal will provide new insights on the mechanisms underlying Meth craving
and relapse. Additionally, under the mentorship of Drs. Shaham, Nestler, and Cowan the proposal will provide
me with an ideal training environment to prepare me for a future independent career as a researcher in an
academic setting who explores basic mechanisms of drug addiction.
线索诱导的药物渴求在戒断后逐渐增加,这种现象被称为“潜伏期”
项目成果
期刊论文数量(0)
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Xuan Anna Li其他文献
Xuan Anna Li的其他文献
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{{ truncateString('Xuan Anna Li', 18)}}的其他基金
March5 and Associated Mitochondrial Dynamics in Incubation of Oxycodone Craving
March5 和相关线粒体动力学在羟考酮渴望孵化中的作用
- 批准号:
10724668 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别: