GABAergic alterations in the BNST to VTA circuit following morphine withdrawal
吗啡戒断后 BNST 至 VTA 回路的 GABA 能变化
基本信息
- 批准号:10607287
- 负责人:
- 金额:$ 3.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-01-01 至 2026-12-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAffectAffective SymptomsAnimalsAnxietyBehaviorBehavior ControlBehavioralBrain regionCellsClinicalCoupledDataDependovirusDiarrheaEconomic BurdenEconomicsElectrophysiology (science)Enterobacteria phage P1 Cre recombinaseEpidemicExperimental DesignsExposure toFemaleFrightFutureGlutamatesHourIncentivesIndividualInterneuronsLabelLiteratureMeasurableMeasuresMediatingMental DepressionModificationMorphineMusNegative ReinforcementsNeurobiologyNeuronsNeurosciencesOpioidOutputPathway interactionsPersonsPharmaceutical PreparationsPhysiologic pulsePopulationPositive ReinforcementsPublishingRelapseReporterResearchRewardsRoleSignal TransductionSleep disturbancesSleeplessnessStructure of terminal stria nuclei of preoptic regionSubstance Withdrawal SyndromeSweatingSymptomsSynapsesSynaptic TransmissionTechnologyTestingTherapeuticTooth structureTrainingTremorUnited StatesVentral Tegmental AreaViralVomitingWeightWhole-Cell RecordingsWithdrawalWithdrawal Symptombehavioral studycomparison controldesigner receptors exclusively activated by designer drugsexperimental studygamma-Aminobutyric Acidimprovedin vivointerestknock-downmalenegative affectneural circuitneurobiological mechanismopioid epidemicopioid exposureopioid misuseopioid overdoseopioid useopioid use disorderopioid withdrawaloptogeneticsphysical symptompreventrelapse preventionskillssleep behaviorsleep patternsleep regulationsmall hairpin RNAsocialtransmission processvoltage clamp
项目摘要
Project Summary/Abstract
The opioid epidemic is a continuously growing problem in the United States and across the world. It has profound
personal, social, and economic consequences. Opioid use can become Opioid Use Disorder (OUD) in many
individuals. OUD consists of several stages, one of which is a highly dysphoric withdrawal syndrome known as
Opioid Withdrawal Syndrome (OWS). The withdrawal symptoms, including sleep dysregulation, and fear of those
symptoms often contributes drastically to relapse. We do not currently understand all of the neurobiological
mechanisms underlying opioid withdrawal, nor how particular circuits are modified by opioid withdrawal. It is well
known, however, that two brain regions, the bed nucleus of the stria terminalis (BNST) and the ventral tegmental
area (VTA), are involved in some capacity. In the two aims of this proposal, the experiments will help to
understand how the pathway between these two regions is modified by opioid withdrawal. Our preliminary data
shows that the GABAergic neurons in the BNST are altered by withdrawal. BNSTGABA neurons make up the bulk
of the BNST neurons projecting to the VTA, where they synapse onto VTAGABA neurons, and have been
implicated in positive reinforcement. This project utilizes viral-manipulations, behavioral studies, and
electrophysiological examinations to carefully and specifically determine the effects of withdrawal in the BNST.
In the second portion of this proposal, the experiments are focused on the output of this pathway in the VTA as
well as a knockdown of this pathway to elucidate the role of this pathway in controlling behavior.
项目总结/文摘
项目成果
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