Aversion signals in the reward system
奖励系统中的厌恶信号
基本信息
- 批准号:10570985
- 负责人:
- 金额:$ 43.38万
- 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:2019-04-15 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AffectAffectiveAnimal ModelAversive StimulusBehaviorBehavior ControlBehavioralClinicalClinical DataCocaine DependenceCognitiveCorpus striatum structureCorticotropin-Releasing HormoneDecision MakingDevelopmentDiseaseDopamineElectrophysiology (science)EmotionalEventExposure toHumanIndividualKnowledgeLife ExperienceMediatingMental DepressionMental disordersModelingMotivationMotorNeuronsNorepinephrineNucleus AccumbensOutputPathway interactionsPeriodicityPersonsPharmaceutical PreparationsPharmacotherapyPropertyPunishmentQuinineRegulationRelapseResearchRewardsScanningShapesSignal TransductionSliceSourceStressStructure of terminal stria nuclei of preoptic regionSubstance abuse problemSwimmingSystemTaste PerceptionTestingVentral Tegmental Areaaddictionbehavior influencebehavioral responsebeta-adrenergic receptorcoping mechanismdopaminergic neurondrug seeking behavioreffective therapyfood restrictiongamma-Aminobutyric Acidgenetic manipulationin vivoinhibitorinnovationmotivated behaviormultidisciplinaryneural circuitneurobiological mechanismneuropsychiatryoptogeneticspharmacologicpreventreceptorrelease factorresponsesocial defeatstressortheories
项目摘要
PROJECT SUMMARY
Aversive environmental events influence the daily lives of all people by altering their emotional states, decision
making, and motivated behavior. For individuals with substance abuse disorders who are attempting to remain
abstinent, these unfortunate events are clinically relevent, as they are frequently cited as a principle cause of
relapse. In order to develop strategies to protect against this important determinant of relapse, it is essential to
characterize the mechanisms through which aversive stimuli influence motivational neural circuitry. To this end,
several decades of research have identified the nucleus accumbens (NAc) as a critical limbic/motor interface,
heavily regulated by dopamine, where affective and associative reward information directly influence behavioral
output. Unfortunately, the manner by which aversive stimuli regulate dopamine signaling remains poorly
understood, with several studies producing conflicting results. We have identified an aversion signal, initiated by
aversion-induced reductions in dopamine concentration, that is associated with increased striatal activity and
drug seeking. The objective of this proposal is to determine how aversive stimuli regulate NAc dopamine
signaling and the mechanisms through which reductions in dopamine alter neuronal activity in the NAc to shape
behavior. To accomplish this objective, the proposal brings together a multi-disciplinary team that will use in vivo
fast scan cyclic voltammetry, in vivo electrophysiology, and ex vivo slice electrophysiology to examine the
independent contributions of reduced dopamine signaling and increased striatal activity to a panel of aversion-
related behaviors, including drug seeking, and both reward and punishment sensitivity. In Aim 1 we will test the
hypothesis that aversive stimuli, via reductions in NAc dopamine activate a subpopulation of aversion-responsive
D2-like receptor-expressing NAc neurons to produce aversion-related behavioral responses. In Aim 2 we test
the hypothesis that aversive stimuli increase corticotropin releasing factor (CRF) in the ventral tegmental area
(VTA) and reduce dopamine in the NAc through a CRFR1- and GABAB receptor-dependent regulation of Girk
channels on VTA DA neurons that project to the NAc shell. In Aim 3 we will examine upstream pathways that
mediate the effects of aversive stimuli on NAc dopamine and behavior and will test the hypothesis that a beta
adrenergic receptor-regulated pathway from the ventral bed nucleus of the stria terminalis to the VTA represents
one such pathway. Understanding how aversive stimuli alter NAc dopamine signaling and how such alterations
encode behavior has implications for understanding and treating a range of stress-related neuropsychiatric
conditions including addiction and depression.
项目总结
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Learned avoidance requires VTA KOR-mediated reductions in dopamine.
习得性回避需要 VTA KOR 介导的多巴胺减少。
- DOI:10.1016/j.neuropharm.2020.107996
- 发表时间:2020
- 期刊:
- 影响因子:4.7
- 作者:Robble,MykelA;Bozsik,MaryE;Wheeler,DanielS;Wheeler,RobertA
- 通讯作者:Wheeler,RobertA
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John R. Mantsch其他文献
Aversion-induced dopamine reductions predict drug-taking and escape behaviors
厌恶诱导的多巴胺减少预测吸毒和逃避行为
- DOI:
10.1038/s41386-025-02101-7 - 发表时间:
2025-04-09 - 期刊:
- 影响因子:7.100
- 作者:
Elaine M. Grafelman;Bridgitte E. Côté;Lisa Vlach;Ella Geise;G. Nino Padula;Daniel S. Wheeler;Matthew C. Hearing;John R. Mantsch;Robert A. Wheeler - 通讯作者:
Robert A. Wheeler
A Computational Approach to Analyzing Spatiotemporal Trends in Gun Violence and Mental Health Disparities among Racialized Communities in US Metropolitan Areas
- DOI:
10.1007/s11524-025-00976-x - 发表时间:
2025-04-22 - 期刊:
- 影响因子:4.100
- 作者:
Fahimeh Mohebbi;Amir Masoud Forati;John R. Mantsch;Madeline Campbell;Rina Ghose - 通讯作者:
Rina Ghose
Glucocorticoid–endocannabinoid interactions in the prelimbic cortex mediate stress-potentiated reinstatement of cocaine seeking
- DOI:
10.1016/j.drugalcdep.2014.09.470 - 发表时间:
2015-01-01 - 期刊:
- 影响因子:
- 作者:
Jayme R. McReynolds;Oliver Vranjkovic;Evan N. Graf;Cecilia J. Hillard;John R. Mantsch - 通讯作者:
John R. Mantsch
Concomitant adrenal hormonal stress responses are required for cocaine-induced locomotor sensitization
- DOI:
10.1016/j.drugalcdep.2014.09.553 - 发表时间:
2015-01-01 - 期刊:
- 影响因子:
- 作者:
David F. Pena;Lisa M. Keller;Conor B. Masterson;Eric J. Cottor;John R. Mantsch - 通讯作者:
John R. Mantsch
John R. Mantsch的其他文献
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{{ truncateString('John R. Mantsch', 18)}}的其他基金
THPB-Containing Herbal Preparations for the Treatment of Drug Abuse
用于治疗药物滥用的含有 THPB 的草药制剂
- 批准号:
7783842 - 财政年份:2009
- 资助金额:
$ 43.38万 - 项目类别:
THPB-Containing Herbal Preparations for the Treatment of Drug Abuse
用于治疗药物滥用的含有 THPB 的草药制剂
- 批准号:
7661335 - 财政年份:2009
- 资助金额:
$ 43.38万 - 项目类别:
THPB-Containing Herbal Preparations for the Treatment of Drug Abuse
用于治疗药物滥用的含有 THPB 的草药制剂
- 批准号:
7839349 - 财政年份:2009
- 资助金额:
$ 43.38万 - 项目类别:
Stress response and HPA regulation in cocaine addiction
可卡因成瘾中的应激反应和 HPA 调节
- 批准号:
6560344 - 财政年份:2002
- 资助金额:
$ 43.38万 - 项目类别:
Stress response and HPA regulation in cocaine addiction
可卡因成瘾中的应激反应和 HPA 调节
- 批准号:
7275351 - 财政年份:2002
- 资助金额:
$ 43.38万 - 项目类别:
Stress response and HPA regulation in cocaine addiction
可卡因成瘾中的应激反应和 HPA 调节
- 批准号:
7106361 - 财政年份:2002
- 资助金额:
$ 43.38万 - 项目类别:
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