Stimulus control of attention in cocaine addiction: role of locus coeruleus
可卡因成瘾中注意力的刺激控制:蓝斑的作用
基本信息
- 批准号:10183212
- 负责人:
- 金额:$ 4.59万
- 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:2019-07-01 至 2022-06-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdaptive BehaviorsArousalAttentionAttenuatedAuditoryAuditory Brainstem ResponsesBehaviorBehavior ControlBehavioralBehavioral ParadigmBrain StemCalciumCell NucleusCocaineCocaine DependenceCollaborationsCommunitiesConditioned StimulusCuesDiseaseElectrophysiology (science)EnvironmentEsthesiaExhibitsFacultyFellowshipFoundationsFutureHeadHumanImageImaging TechniquesIndividualIndividual DifferencesMediatingMemoryMentorshipMicroscopeNational Research Service AwardsNeocortexNeurobiologyNeuronsNorepinephrineOccupationalOutcome StudyPharmaceutical PreparationsPhasePhysiologyProcessPropertyPsychological reinforcementRattusRecoveryRelapseResearchResearch PersonnelResolutionRewardsRodent ModelRoleScientistSelf AdministrationSensorySensory ProcessStimulusStructureStudentsSystemTechniquesTestingTherapeuticTrainingTyrosine 3-MonooxygenaseVirusWateraddictionattentional biasattentional controlcareercocaine exposurecocaine self-administrationcocaine useconditioningcravingeffective therapyexperienceexperimental studyimprovedin vivo calcium imaginglocus ceruleus structuremembermotivated behaviorneural correlateneuromechanismnovelnovel therapeutic interventionpreconditioningpreventprogramspublic health relevancereinforced behaviorrelating to nervous systemresponsereuptakeselective expressionsensory systemsocialsocietal costssuccessundue influence
项目摘要
Project Summary/Abstract
Salient environmental stimuli can capture attention and drive behavior; this process, vital for guiding
adaptive behavior, is called stimulus control. Stimulus control can become maladaptive in disease states, such
as cocaine addiction, where cocaine-associated stimuli can wield undue influence and disrupt ongoing preferred
behavior (i.e. occupational or social activities) and efforts to remain drug-free. While altered stimulus control is
well-understood to contribute to cocaine addiction, the neural mechanisms underlying this process are poorly
understood. The locus coeruleus (LC) is a neural structure, which modulates attention, sensation, and behavioral
control and is strongly effected by cocaine. Thus, the LC may be at the center of maladaptive stimulus control in
cocaine addiction. Stimulus encoding in LC and downstream sensory systems is known to be critical for stimulus-
guided behavior although it is not known if cocaine-associated stimuli are encoded in these systems. The
research plan proposed in this NRSA will elucidate the role of LC in encoding an auditory cocaine-stumulus and
examine whether there is a causal role for LC in mediating control of behavior by this stimulus. We will employ
a behavioral paradigm in rats which assesses stimulus control of water-reinforced behavior by an auditory
cocaine-stimulus. Aim 1 will use cellular resolution calcium imaging and electrophysiology to examine neural
correlates of stimulus control in the LC and auditory brainstem respectively. Aim 2 will use a chemogenetic
approach to selectively inhibit LC activity during acquisition or expression of conditioned stimulus control by a
cocaine-stimulus in order establish a causal role for LC in these processes. Combined, these experiments have
the potential to inform therapies aimed at targeting LC to attenuate maladaptive stimulus-driven behavior in
cocaine addiction.
Furthermore, the proposed fellowship will provide me with a strong foundation for a career as an
independent investigator focused on the neurobiological and behavioral underpinnings of addiction. The training
environment described in this proposal will incorporate faculty-student mentorships and collaborations aimed at
providing me with scientific training across the domains central to this project including LC physiology, calcium
imaging techniques, and sensory processing. Additionally, the training plan will provide me with professional
training which will prepared me for my future as I establish my own independent research program. As a whole,
this Fellowship has significant potential to produce both scientific findings relevant to treatment of addiction and
also a scientist well-equipped to become an outstanding member of the addiction research community.
项目概要/摘要
显着的环境刺激可以吸引注意力并驱动行为;这个过程对于指导至关重要
适应性行为,称为刺激控制。在疾病状态下,刺激控制可能会变得适应不良,例如
作为可卡因成瘾,与可卡因相关的刺激可能会产生不当影响并破坏持续的偏好
行为(即职业或社会活动)和保持不吸毒的努力。虽然改变刺激控制是
人们已充分了解可卡因成瘾的原因,但这一过程背后的神经机制却知之甚少。
明白了。蓝斑 (LC) 是一种神经结构,可调节注意力、感觉和行为
控制并受到可卡因的强烈影响。因此,LC 可能处于适应不良刺激控制的中心。
可卡因成瘾。 LC 和下游感觉系统中的刺激编码对于刺激至关重要
尽管尚不清楚可卡因相关刺激是否被编码在这些系统中,但仍可引导行为。这
本 NRSA 中提出的研究计划将阐明 LC 在编码听觉可卡因刺激中的作用,以及
检查 LC 在调节这种刺激的行为控制中是否具有因果作用。我们将聘用
大鼠的行为范例,通过听觉评估水强化行为的刺激控制
可卡因刺激。目标 1 将使用细胞分辨率钙成像和电生理学来检查神经
分别与 LC 和听觉脑干中的刺激控制相关。目标 2 将使用化学遗传学
在条件刺激控制的获取或表达过程中选择性抑制LC活性的方法
可卡因刺激,以确定 LC 在这些过程中的因果作用。综合起来,这些实验
为针对 LC 的治疗提供信息的潜力,以减轻刺激驱动的适应不良行为
可卡因成瘾。
此外,拟议的奖学金将为我的职业生涯提供坚实的基础
独立调查员专注于成瘾的神经生物学和行为基础。培训内容
本提案中描述的环境将包括师生指导和合作,旨在
为我提供该项目核心领域的科学培训,包括 LC 生理学、钙学
成像技术和感觉处理。此外,培训计划将为我提供专业的
当我建立自己的独立研究计划时,培训将为我的未来做好准备。整体而言,
该奖学金具有产生与成瘾治疗相关的科学发现和
他也是一位科学家,有能力成为成瘾研究界的杰出成员。
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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{{ truncateString('Mark Anton Presker', 18)}}的其他基金
Stimulus control of attention in cocaine addiction: role of locus coeruleus
可卡因成瘾中注意力的刺激控制:蓝斑的作用
- 批准号:
9760777 - 财政年份:2019
- 资助金额:
$ 4.59万 - 项目类别:
Investigating the role of locus coeruleus in conditioned cocaine-stimulus control of attention
研究蓝斑在条件性可卡因刺激注意力控制中的作用
- 批准号:
10669917 - 财政年份:2019
- 资助金额:
$ 4.59万 - 项目类别:
Stimulus control of attention in cocaine addiction: role of locus coeruleus
可卡因成瘾中注意力的刺激控制:蓝斑的作用
- 批准号:
9980176 - 财政年份:2019
- 资助金额:
$ 4.59万 - 项目类别:
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