Dopamine modulation for the treatment of chronic dysfunction due to traumatic brain injury
多巴胺调节治疗创伤性脑损伤引起的慢性功能障碍
基本信息
- 批准号:10163928
- 负责人:
- 金额:--
- 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:2019-05-15 至 2021-05-02
- 项目状态:已结题
- 来源:
- 关键词:AffectAggressive behaviorAgonistAmericanAmphetaminesAnimal ModelAnimalsAreaAttention deficit hyperactivity disorderAutomobile DrivingBehavior TherapyBehavioral AssayBiological AssayBrainBrain InjuriesCaregiversCellsChemicalsChronicClinicalCommunitiesCuesDataDecision MakingDevelopmentDiseaseDopamineDopaminergic AgentsEnvironmentFunctional disorderGamblingGeneral PopulationGoalsHumanImpaired cognitionImpairmentImpulsivityIncidenceIndividualInjuryIowaKnowledgeLifeMediatingMediator of activation proteinMedicalModalityModelingOutcomePatientsPersonsPharmaceutical PreparationsPharmacologic SubstancePharmacologyPhasePopulationPositioning AttributePredispositionProsencephalonProteinsPsychiatric therapeutic procedurePsychological reinforcementPublishingQuality of lifeRattusRehabilitation OutcomeRehabilitation therapyReportingResearchRitalinRodentRoleSelf PerceptionSeriesSignal TransductionSpecial PopulationSurvivorsSymptomsSystemTBI PatientsTBI treatmentTherapeuticTherapeutic AgentsTrainingTranslationsTraumatic Brain InjuryTreatment EfficacyUnited StatesWorkaddictionanalogassociated symptombaseclinically relevantdisabilitydopamine systemefficacious treatmentefficacy evaluationefficacy testingexperienceexperimental studyfrontal lobeimprovedimproved functioningmotivated behaviornegative affectneglectneuroregulationneurotransmissionpre-clinical researchpsychiatric symptompsychostimulantreceptorrecruitrelating to nervous systemresponsetherapeutic evaluationtherapeutic targettherapeutically effective
项目摘要
Project Summary/Abstract
More than 2.8 million traumatic brain injuries (TBIs) occur annually, making this one of the most pressing
challenges facing the medical community. Survivors of TBI often experience chronic psychiatric symptoms
such as increased risky decision-making and impulsivity, yet there are no treatments specific to this large
population. These deficits affect individuals across all aspects of everyday life, often leading to reduced quality
of life for caregivers or those surrounding the person. A potential major contributor to this enduring dysfunction
is reduced dopamine neurotransmission, which mediates many core motivated behaviors in humans and
animals. Because of reductions in dopamine, these changes may alter the efficacy of rehabilitative efforts and
therapeutic drugs, making patients with TBI a special population in this regard. Thus, the goal of this project is
to investigate potential treatments for psychiatric-like deficits arising from chronic TBI, focusing on modulation
of dopamine systems, with the hypothesis that augmentation of dopamine will improve function. This will be
investigated across three aims, each with different treatment modalities, using a rat model of TBI. Proposed
studies will use an analog of the Iowa Gambling Task, known as the Rodent Gambling Task, to concurrently
assess risky decision-making and impulsivity after TBI. Aim 1 will investigate changes in sensitivity to
environmental contingencies to understand shifts in efficacy of rehabilitative training in humans. A series of
experiments will determine whether cueing of outcomes, a known means of stimulating dopamine responses,
can rescue decision-making ability. Aim 2 will test the efficacy of multiple therapeutic drugs. It will compare
how effective receptor-specific drugs are compared with general dopaminergic agents and what specific
changes occur to brain levels of dopamine-related proteins in the chronic injury period. Aim 3 will evaluate the
efficacy and mechanism of transcranial direct-current stimulation (tDCS) as a form of neural modulation. Prior
research has suggested that tDCS increases dopamine levels, but parameters have not been explored for
brain-injured subjects. To verify that dopamine is driving beneficial effects of tDCS, chemogenetic inhibition of
dopamine cells will be performed in the frontal cortex. These studies will advance fundamental understanding
of mechanisms of dysfunction after TBI, identify the efficacy of three different therapeutic modalities, and
determine the degree to which dopamine represents a relevant clinical target for chronic dysfunction after
injury.
项目总结/文摘
项目成果
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Cole Vonder Haar其他文献
Cole Vonder Haar的其他文献
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{{ truncateString('Cole Vonder Haar', 18)}}的其他基金
Dopamine modulation for the treatment of chronic dysfunction due to traumatic brain injury
多巴胺调节治疗创伤性脑损伤引起的慢性功能障碍
- 批准号:
10400280 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Dopamine modulation for the treatment of chronic dysfunction due to traumatic brain injury
多巴胺调节治疗创伤性脑损伤引起的慢性功能障碍
- 批准号:
10616545 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Dopamine modulation for the treatment of chronic dysfunction due to traumatic brain injury
多巴胺调节治疗创伤性脑损伤引起的慢性功能障碍
- 批准号:
10594159 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Dopamine modulation for the treatment of chronic dysfunction due to traumatic brain injury
多巴胺调节治疗创伤性脑损伤引起的慢性功能障碍
- 批准号:
10426388 - 财政年份:2019
- 资助金额:
-- - 项目类别:
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