Vulnerability biomarkers for cocaine abuse and relapse

描述(申请人提供)：滥用可卡因是一个普遍和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的差异，但我们还不清楚调节可卡因滥用和成瘾原因的个体差异的机制。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，会低比率地消费可卡因，而另一些人则相对容易受到可卡因的影响，会高比率地消费可卡因。在目前的提案中，我们将评估几个新的生物标记物，它们可以预测一个人滥用可卡因或戒除后复发的易感性。我们将使用药物自我给药(SA)和在非人类灵长类动物中恢复以前药物维持的行为来评估这些过程，因为这些都是公认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大脑蛋白质的可用性、可卡因的急性大脑激活效应或功能麸皮网络的完整性是否预测可卡因滥用和复发。我们相信，这些研究将具有重要的公共卫生影响，因为这些技术可以转化为用于人类受试者，它们将允许医生根据可卡因依赖患者的当前状况个性化定制治疗计划。

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.