Vulnerability biomarkers for cocaine abuse and relapse

说明（由申请人提供）：滥用可卡因是一个广泛和严重有害的公共卫生问题。虽然已经确定个体对可卡因暴露的反应存在很大的差异，但我们还不了解在可卡因滥用和成瘾的病因学中介导个体差异的机制。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，吸食可卡因的频率很低，而另一些人相对容易受到可卡因的影响，吸食可卡因的频率很高。在目前的建议中，我们将评估几种新的生物标志物，这些生物标志物可能预测个体滥用可卡因或戒断后复发的脆弱性。我们将在非人类灵长类动物中使用药物自我给药（SA）和恢复先前药物维持的行为来评估这些过程，因为这些是已经建立好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的方式确定特定脑蛋白的可用性、可卡因的急性脑激活效应或功能性脑网络的完整性是否预测可卡因滥用和复发。我们认为，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人类受试者的使用，它们将允许医生根据可卡因依赖患者的现状量身定制治疗计划。

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.