Vulnerability biomarkers for cocaine abuse and relapse

可卡因滥用和复发的脆弱性生物标志物

• 批准号: 8495966
• 负责人: LEONARD L HOWELL
• 金额: $ 21.42万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8495966
• 关键词: Abstinence; Acute; Animal Model; Area; Attenuated; Behavior; Biological Markers; Brain; Chronic; Cocaine; Cocaine Abuse; Cocaine Dependence; Consumption; Data; Development; Disease; Dopamine D2 Receptor; Drug Exposure; Drug usage; Etiology; Functional Magnetic Resonance Imaging; HTR2A gene; Individual; Individual Differences; Lead; Literature; Macaca mulatta; Magnetic Resonance Imaging; Maintenance; Mediating; Metric; Modeling; Neurobiology; Patients; Pattern; Pharmaceutical Preparations; Physicians; Positron-Emission Tomography; Predisposing Factor; Prefrontal Cortex; Procedures; Process; Proteins; Psychological reinforcement; Public Health; Receptor Activation; Recording of previous events; Relapse; Resistance; Self Administration; Serotonin; Techniques; Translating; awake; base; cocaine exposure; effective therapy; frontal lobe; human subject; interest; neuroimaging; nonhuman primate; novel; public health relevance; receptor; research study; response; success; treatment planning

DESCRIPTION (provided by applicant): Abuse of cocaine is a widespread and severely deleterious public health problem. Although it is well established that there is substantial variability in an individual's response to cocaine exposure, we do not yet understand the mechanisms that mediate individual differences in the etiology of cocaine abuse and addiction. In particular, we do not understand why some individuals are resistant to the effects of cocaine and will consume cocaine at low rates whereas other individuals are relatively vulnerable to the effects of cocaine and will consume cocaine at high rates. In the present proposal, we will evaluate several novel biomarkers that may predict the vulnerability of an individual to abuse cocaine or to relapse following abstinence. We will evaluate these processes using drug self-administration (SA) and reinstatement of previously drug-maintained behavior in nonhuman primates, as these are well established animal models of cocaine abuse and relapse. Moreover, we propose to determine, in a highly systematic manner, whether the availability of specific brain proteins, the acute brain activational effects of cocaine, or the integrity of functional bran networks predicts cocaine abuse and relapse. We believe that these studies will have important public health implications because these techniques can be translated into use in human subjects, and they will allow physicians to individually tailor treatment plans based on the current status of the cocaine-dependent patient.

描述（由申请人提供）：滥用可卡因是一个广泛且严重有害的公共卫生问题。尽管众所周知，个体对可卡因暴露的反应存在很大差异，但我们尚不了解介导可卡因滥用和成瘾病因学个体差异的机制。特别是，我们不明白为什么有些人对可卡因的影响有抵抗力，并且会以较低的比例消费可卡因，而其他人则相对容易受到可卡因的影响，并会以较高的比例消费可卡因。在本提案中，我们将评估几种新颖的生物标志物，这些标志物可以预测个体滥用可卡因或戒断后复发的脆弱性。我们将使用药物自我给药（SA）和恢复非人类灵长类动物先前药物维持的行为来评估这些过程，因为这些是已建立的可卡因滥用和复发的动物模型。此外，我们建议以高度系统化的方式确定特定脑蛋白的可用性、可卡因的急性脑激活作用或功能性麸皮网络的完整性是否可以预测可卡因滥用和复发。我们相信这些研究将对公共卫生产生重要影响，因为这些技术可以转化为在人类受试者中的使用，并且它们将允许医生根据可卡因依赖患者的当前状况单独制定治疗计划。