Targeting dopamine D3 receptors in cocaine addiction
靶向可卡因成瘾中的多巴胺 D3 受体
基本信息
- 批准号:9926357
- 负责人:
- 金额:$ 2.01万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-04-01 至 2021-01-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdmission activityAffectAffectiveAffinityAftercareAgonistAllelesAmygdaloid structureAnimalsAttentionBehavioralBrainCessation of lifeClinicalClinical TrialsCocaineCocaine DependenceCuesDataDevelopmentDisadvantagedDiseaseDopamineDorsalDoseDrug usageEpidemicFDA approvedFunctional Magnetic Resonance ImagingFutureGenesGlobus PallidusHospitalsHumanImageImaging DeviceIndividualInpatientsKnowledgeLaboratoriesLinkMeasuresMorbidity - disease rateMotivationNucleic Acid Regulatory SequencesPainParticipantPatientsPerformancePharmaceutical PreparationsPharmacogeneticsPhasePlacebosPrefrontal CortexPublic HealthPumpRandomizedRelapseRewardsRisk FactorsRisk-TakingSavingsSourceSpeedSystemTestingTranslationsVentral Striatumaddictionbehavior measurementbehavioral responseclinical efficacycocaine usecostdesigndopamine D3 receptordopamine transporterdrug rewardefficacy trialendophenotypeexperiencegenetic variantimprovedinnovationmortalityneurobehavioralneuroimagingneurotransmissionnovelplacebo grouppre-clinicalpublic health relevancereceptorrecruitrelapse patientsresponsetool
项目摘要
DESCRIPTION (provided by applicant): After three decades of a national cocaine epidemic, and many clinical trials, there are no FDA-approved medications for this painful and costly addiction. Relapse rates remain stubbornly high, and can approach 80% at 6 months post- treatment. The poor translation from elegant preclinical (animal) studies to clinical benefit may be due, in part, to limited knowledge of the candidate medications' ability to engage relapse-relevant brain targets in humans -- prior to initiating large-scale clinical trials. The proposed project will address this critical knowledge gap, using NEURO-imaging (fMRI) tools, combined with hypothesis-driven NEURO-behavioral probes, to determine whether BP1.4979, a new candidate medication specifically targeting the dopamine D3 receptor, can impact relapse-relevant endophenotypes (e.g., cue-triggered activation of motivational circuitry; activation of inhibitory circuitry) at a dose under consideration for future clinical efficacy trials. D3 receptos have strong promise as addiction targets, but safe, D3-specific agents are very rare. Seventy-two imaging- eligible cocaine inpatients will be randomized either to the DA D3 partial agonist, BP1.4979 (30 mg), or to placebo. Prior to, and following, induction onto medication or placebo, the participants will be tested with our hypothesis-driven (brain, Specific Aim 1, and behavioral, Specific Aim 2) probes for reward ("GO!") and inhibition ("STOP"). The over-arching hypothesis is that the DA D3-modulating medication will blunt the brain- behavioral response to our reward-related "GO!" probes, while potentially improving the brain-behavioral response to our "STOP" probes. Our design also offers the natural opportunity to explore (Exploratory Aim) whether the medication response on the brain-behavioral measures is related to individual genetic variants affecting (directly or indirectly) DA neurotransmission, and to cocaine use during a brief but informative "relapse window" following the inpatient stay. An experienced team, innovative probes, and a novel (previously unavailable) D3 medication are strengths of the proposal.
描述(由适用提供):经过三十年的全国可卡因流行病,许多临床试验,没有FDA批准的药物来使这种痛苦和昂贵的成瘾。复发率保持顽固,在治疗后6个月时可以接近80%。从优雅的临床前(动物)研究到临床益处的不良翻译可能部分是由于对候选药物在人体中参与相关的大脑目标的能力有限 - 在开始大规模临床试验之前。 The proposed project will address this critical knowledge gap, using NEURO-imaging (fMRI) tools, combined with hypothesis-driven NEURO-behavioral problems, to determine whether BP1.4979, a new candidate medication specifically targeting the dopamine D3 receptor, can impact relay-relevant endophenotypes (e.g., cue-triggered activation of motivational circuitry; activation of inhibitory电路)正在考虑未来的临床效率试验的剂量。 D3受体作为成瘾靶标具有很大的希望,但是安全的D3特异性药物非常罕见。 72个成像可卡因住院患者将随机分为DA D3部分激动剂BP1.4979(30 mg)或安慰剂。在对药物或安慰剂的诱导之前和之后,将通过我们的假设驱动的(大脑,特定目标1和行为的特定目标2)奖励(“ GO!”)和抑制(“停止”)对参与者进行测试。总结的假设是,DA D3调节药物将使大脑行为反应对我们与奖励相关的“ GO!”的反应钝化。问题,同时有可能改善对我们“停止”问题的大脑行为反应。我们的设计还提供了自然的机会来探索(探索性目的),是否与脑行为措施的药物反应与影响(直接或间接)DA神经传递的个体遗传变异有关,以及在住院住所住院后短暂但信息丰富的“复发窗口”中使用可卡因。一支经验丰富的团队,创新的问题和小说(以前不可用的)D3药物是该提议的优势。
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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Anna Rose Childress其他文献
Can we use cue-related brain responses to predict which cocaine patients will take more risks?
- DOI:
10.1016/j.drugalcdep.2014.09.489 - 发表时间:
2015-01-01 - 期刊:
- 影响因子:
- 作者:
Zachary A. Monge;K. Jagannathan;Jesse Suh;Ronald Ehrman;Kimberly A. Young;Teresa Franklin;Daniel Langleben;Charles P. O’Brien;Anna Rose Childress - 通讯作者:
Anna Rose Childress
Baclofen, a GABA B Agonist, reduces risk-taking and reveals the relationship between brain responses to drug cues and risk-taking in cocaine-addicted patients
- DOI:
10.1016/j.drugalcdep.2014.02.684 - 发表时间:
2014-07-01 - 期刊:
- 影响因子:
- 作者:
Kimberly A. Young;Y. Li;D.C.S. Roberts;C. Lejuez;Teresa R. Franklin;Jesse Suh;M. Goldman;Kyle M. Kampman;Reagan R. Wetherill;C.P. O’Brien;Anna Rose Childress - 通讯作者:
Anna Rose Childress
Frontal vs. limbic predictors of inhibitory success in addiction
- DOI:
10.1016/j.drugalcdep.2014.02.112 - 发表时间:
2014-07-01 - 期刊:
- 影响因子:
- 作者:
Anna Rose Childress;Y. Li;M. Goldman;J.J. Suh;R. Ehrman;S. Lam;Z. Singer;Teresa R. Franklin;D. Langleben;K. Young;Reagan R. Wetherill;Michael J. Gawrysiak;C.P. O’Brien - 通讯作者:
C.P. O’Brien
A higher hill to climb! Older cocaine-addicted patients viewing 500 ms cocaine cues have reduced activation of modulatory circuits and increased activation of motivational circuits
- DOI:
10.1016/j.drugalcdep.2015.07.423 - 发表时间:
2015-11-01 - 期刊:
- 影响因子:
- 作者:
Zachary A. Monge;K. Jagannathan;Jesse Suh;Ronald Ehrman;Ze Wang;Teresa Franklin;Reagan R. Wetherill;Kimberly A. Young;Michael J. Gawrysiak;Daniel Langleben;Charles P. O’Brien;Anna Rose Childress - 通讯作者:
Anna Rose Childress
Differential brain response to successful and failed response inhibition: Cocaine-dependent vs. healthy subjects
- DOI:
10.1016/j.drugalcdep.2015.07.582 - 发表时间:
2015-11-01 - 期刊:
- 影响因子:
- 作者:
Jesse Suh;K. Jagannathan;Ronald Ehrman;Marina Goldman;Zachary A. Monge;Elliott Berkowitz-Sturgis;Teresa Franklin;Kathleen Marquez;Regina Szucs-Reed;Charles P. O’Brien;Anna Rose Childress - 通讯作者:
Anna Rose Childress
Anna Rose Childress的其他文献
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{{ truncateString('Anna Rose Childress', 18)}}的其他基金
A Clinical Laboratory with Integrated Neuroscience (CLIN) for Early Evaluation of Medications for Substance Use Disorders
综合神经科学 (CLIN) 临床实验室,用于药物滥用障碍药物的早期评估
- 批准号:
10395761 - 财政年份:2021
- 资助金额:
$ 2.01万 - 项目类别:
A Clinical Laboratory with Integrated Neuroscience (CLIN) for Early Evaluation of Medications for Substance Use Disorders
综合神经科学 (CLIN) 临床实验室,用于药物滥用障碍药物的早期评估
- 批准号:
10348202 - 财政年份:2020
- 资助金额:
$ 2.01万 - 项目类别:
A Clinical Laboratory with Integrated Neuroscience (CLIN) for Early Evaluation of Medications for Substance Use Disorders
综合神经科学 (CLIN) 临床实验室,用于药物滥用障碍药物的早期评估
- 批准号:
10576815 - 财政年份:2020
- 资助金额:
$ 2.01万 - 项目类别:
A Clinical Laboratory with Integrated Neuroscience (CLIN) for Early Evaluation of Medications for Substance Use Disorders
综合神经科学 (CLIN) 临床实验室,用于药物滥用障碍药物的早期评估
- 批准号:
9895139 - 财政年份:2020
- 资助金额:
$ 2.01万 - 项目类别:
Targeting dopamine D3 receptors in cocaine addiction
靶向可卡因成瘾中的多巴胺 D3 受体
- 批准号:
9249538 - 财政年份:2016
- 资助金额:
$ 2.01万 - 项目类别:
T32 Translational Addiction Research Fellowship Program
T32 转化成瘾研究奖学金计划
- 批准号:
9393067 - 财政年份:2016
- 资助金额:
$ 2.01万 - 项目类别:
Weight History, Brain Activation to Food Cues and Eating Disorder Psychopathology
体重史、食物线索的大脑激活和饮食失调精神病理学
- 批准号:
8678241 - 财政年份:2014
- 资助金额:
$ 2.01万 - 项目类别:
Weight History, Brain Activation to Food Cues and Eating Disorder Psychopathology
体重史、食物线索的大脑激活和饮食失调精神病理学
- 批准号:
9076365 - 财政年份:2014
- 资助金额:
$ 2.01万 - 项目类别:
Do brain differences influence HIV risk behavior? A study of young urban women
大脑差异会影响艾滋病毒危险行为吗?
- 批准号:
8513416 - 财政年份:2012
- 资助金额:
$ 2.01万 - 项目类别:
Do brain differences influence HIV risk behavior? A study of young urban women
大脑差异会影响艾滋病毒危险行为吗?
- 批准号:
8330061 - 财政年份:2012
- 资助金额:
$ 2.01万 - 项目类别:
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