Targeting neural, behavioral and pharmacological mechanisms of drug memories in cocaine addiction
针对可卡因成瘾药物记忆的神经、行为和药理学机制
基本信息
- 批准号:10447976
- 负责人:
- 金额:$ 25.35万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-30 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AbstinenceAlcoholsAnimalsBehavior ControlBehavioralCannabisChronic DiseaseCigarette SmokerClinicalCocaineCocaine DependenceCocaine use disorderCognitiveCrossover DesignCuesDevelopmentDiseaseDopamine AgonistsDouble-Blind MethodDrug AddictionDrug usageEmotionalExhibitsExtinction (Psychology)Functional Magnetic Resonance ImagingFutureGalvanic Skin ResponseGoalsGoldHeroinHumanImpairmentIndividualInterventionKnowledgeLeadLearningMagnetic Resonance ImagingMeasuresMedicineMemoryMethodsModificationNeurobiologyNeuronal PlasticityNeurosciencesNootropic AgentsOpioidOralOutcomePharmaceutical PreparationsPharmacologyPlacebo ControlPlacebosPost-Traumatic Stress DisordersPrefrontal CortexProcessPsychopathologyPsychophysiologyReactionRelapseReportingResearchRetrievalRitalinSeriesSubstance Use DisorderTestingTimeTrainingTraumatic Brain Injuryaddictionattenuationbasebehavioral pharmacologybehavioral studyblood oxygen level dependentclassical conditioningcognitive enhancementcognitive rehabilitationcognitive trainingconditioned fearcravingdesigndrug of abusedrug reinforcementexperienceimaging studyimprovedimproved outcomememory processneural circuitneural correlateneuroimagingneuromechanismnovelnovel strategiesoutcome predictionpreventrelating to nervous systemremediationresponsesubstance usesuccess
项目摘要
This R21 application aims to identify the neural, behavioral, and pharmacological mechanisms promoting
diminished expression of drug-related memories in human cocaine addiction. Drug addiction is a chronic disorder
where cues previously associated with drug reinforcement (e.g., pipe) evoke salient and pervasive memories of
the drug experience. These memories contribute to craving, precipitating relapse even after long periods of
abstinence. Traditional cue-exposure therapies aimed at extinguishing these provoking effects of drug cues have
therefore been widely used. However, these therapies do not usually prevent relapse, highlighting the need for
alternative strategies. The goal of this exploratory project is to identify a pharmacologically-enhanced learning-
based behavioral approach and its underlying neural mechanisms that could ultimately be targeted for
decreasing craving and relapse in human addiction. Our behavioral approach, designed to interfere with the
return of drug memories in individuals with cocaine use disorders (iCUD), builds on animal and human behavioral
studies showing that retrieval of drug-cue memories 10 min before their extinction results in long-lasting
attenuation of cue-induced drug-seeking and craving. This approach thus takes advantage of cutting-edge
research on the mechanisms underlying memory reconsolidation, a time-dependent process in which specific
consolidated memories become transiently unstable shortly after their retrieval, making them amenable to either
disruption or strengthening. Since iCUD exhibit deficits in learning and memory and underlying neural substrates,
we will enhance this behavioral approach pharmacologically, using methylphenidate (MPH, a dopamine agonist)
as a cognitive enhancer to promote learning-induced neural plasticity in iCUD. Choice of MPH is based on a
series of neuroimaging studies in iCUD where we reported normalization of function (behavioral and neural) on
other relevant cognitive-behavioral tasks. Specifically, in this functional magnetic resonance imaging (fMRI)
study, in a within-subjects placebo-controlled double-blind cross-over design, oral MPH (20 mg) will be
administered to iCUD to peak during the retrieval of a drug-cue memory before extinction; in addition to fMRI
activations, skin conductance responses (SCR, acquired simultaneously) will serve as the psychophysiological
indicators of memory modification. Assessments of interference with the return of drug-cue memories via SCR
and craving will be conducted the day following MRI. This project will delineate the neural correlates of a
pharmacologically-enhanced behavioral approach to decrease drug memories and craving in iCUD, which could
be ultimately used to develop effective cue-exposure therapies. If, compared to standard therapies, these novel
approaches are later shown to improve clinical outcome in iCUD, this exploratory study may pave the way
towards enhancing the efficacy of cue-exposure therapy in reducing cue-induced craving and relapse, ideal also
for personal medicine purposes. Results from this basic study could generalize to other types of drugs of abuse
or to behavioral addictions.
本R21应用程序旨在确定神经,行为和药理学机制促进
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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Rita Z Goldstein其他文献
Oral Methylphenidate Normalizes Cingulate Activity and Decreases Impulsivity in Cocaine Addiction During an Emotionally Salient Cognitive Task
在一项情感显著的认知任务中,口服哌甲酯可使扣带回活动正常化,并降低可卡因成瘾者的冲动性
- DOI:
10.1038/npp.2010.145 - 发表时间:
2010-11-30 - 期刊:
- 影响因子:7.100
- 作者:
Rita Z Goldstein;Nora D Volkow - 通讯作者:
Nora D Volkow
Rita Z Goldstein的其他文献
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{{ truncateString('Rita Z Goldstein', 18)}}的其他基金
Brain-to-brain neurofeedback during naturalistic dynamic stimuli to reduce craving in heroin addiction
自然动态刺激期间的脑对脑神经反馈可减少海洛因成瘾的渴望
- 批准号:
10725836 - 财政年份:2023
- 资助金额:
$ 25.35万 - 项目类别:
Targeting neural, behavioral and pharmacological mechanisms of drug memories in cocaine addiction
针对可卡因成瘾药物记忆的神经、行为和药理学机制
- 批准号:
10707903 - 财政年份:2022
- 资助金额:
$ 25.35万 - 项目类别:
Sex differences in the neural correlates underlying impairments in response inhibition and salience attribution in cocaine addiction
神经系统中的性别差异与可卡因成瘾的反应抑制和显着性归因的潜在损伤相关
- 批准号:
9913128 - 财政年份:2020
- 资助金额:
$ 25.35万 - 项目类别:
Sex differences in the neural correlates underlying impairments in response inhibition and salience attribution in cocaine addiction
神经系统中的性别差异与可卡因成瘾的反应抑制和显着性归因的潜在损伤相关
- 批准号:
10561729 - 财政年份:2020
- 资助金额:
$ 25.35万 - 项目类别:
Sex differences in the neural correlates underlying impairments in response inhibition and salience attribution in cocaine addiction
神经系统中的性别差异与可卡因成瘾的反应抑制和显着性归因的潜在损伤相关
- 批准号:
10358597 - 财政年份:2020
- 资助金额:
$ 25.35万 - 项目类别:
Neuroimaging response inhibition and salience attribution changes during mindfulness-based treatment of human heroin addiction
基于正念的人类海洛因成瘾治疗过程中神经影像反应抑制和显着性归因的变化
- 批准号:
9763882 - 财政年份:2019
- 资助金额:
$ 25.35万 - 项目类别:
Diagnostic and prognostic biomarkers for subtypes of addiction-related circuit dysfunction
成瘾相关回路功能障碍亚型的诊断和预后生物标志物
- 批准号:
10414018 - 财政年份:2019
- 资助金额:
$ 25.35万 - 项目类别:
Diagnostic and prognostic biomarkers for subtypes of addiction-related circuit dysfunction
成瘾相关回路功能障碍亚型的诊断和预后生物标志物
- 批准号:
10177987 - 财政年份:2019
- 资助金额:
$ 25.35万 - 项目类别:
Neuroimaging response inhibition and salience attribution changes during mindfulness-based treatment of human heroin addiction
基于正念的人类海洛因成瘾治疗过程中神经影像反应抑制和显着性归因的变化
- 批准号:
10188440 - 财政年份:2019
- 资助金额:
$ 25.35万 - 项目类别:
Neuroimaging response inhibition and salience attribution changes during mindfulness-based treatment of human heroin addiction
基于正念的人类海洛因成瘾治疗过程中神经影像反应抑制和显着性归因的变化
- 批准号:
10646215 - 财政年份:2019
- 资助金额:
$ 25.35万 - 项目类别:
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