Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425.
Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425
Proc Natl Acad Sci U S A. 2014 Aug 12;111(32):11822-7. doi: 10.1073/pnas.1406324111. Epub 2014 Jul 28.
Development of new treatments for drug addiction will depend on high-throughput screening in animal models. However, an addiction biomarker fit for rapid testing, and useful in both humans and animals, is not currently available. Economic models are promising candidates. They offer a structured quantitative approach to modeling behavior that is mathematically identical across species, and accruing evidence indicates economic-based descriptors of human behavior may be particularly useful biomarkers of addiction severity. However, economic demand has not yet been established as a biomarker of addiction-like behavior in animals, an essential final step in linking animal and human studies of addiction through economic models. We recently developed a mathematical approach for rapidly modeling economic demand in rats trained to self-administer cocaine. We show here that economic demand, as both a spontaneous trait and induced state, predicts addiction-like behavior, including relapse propensity, drug seeking in abstinence, and compulsive (punished) drug taking. These findings confirm economic demand as a biomarker of addiction-like behavior in rats. They also support the view that excessive motivation plays an important role in addiction while extending the idea that drug dependence represents a shift from initially recreational to compulsive drug use. Finally, we found that economic demand for cocaine predicted the efficacy of a promising pharmacotherapy (oxytocin) in attenuating cocaine-seeking behaviors across individuals, demonstrating that economic measures may be used to rapidly identify the clinical utility of prospective addiction treatments.
开发新的药物成瘾治疗方法将取决于动物模型中的高通量筛选。然而,目前还没有适合快速检测的成瘾生物标志物,也没有既适用于人类又适用于动物的生物标志物。经济模型是很有前途的候选者。它们为建模行为提供了一种结构化的定量方法,这种方法在物种间是数学上相同的,并且越来越多的证据表明,基于经济的人类行为描述符可能是成瘾严重程度的特别有用的生物标志物。然而,经济需求尚未被确立为动物成瘾样行为的生物标志物,这是通过经济模型将动物和人类成瘾研究联系起来的最后一个重要步骤。我们最近开发了一种快速模拟可卡因自我给药训练大鼠经济需求的数学方法。我们在这里表明,经济需求作为一种自发的特征和诱导状态,预测了成瘾样行为,包括复发倾向、禁欲期的觅药行为和强迫(受惩罚)药物摄入。这些发现证实了经济需求作为大鼠成瘾样行为的生物标志物。它们还支持这样一种观点,即过度的动机在成瘾中起着重要作用,同时扩展了这样一种观点,即药物依赖代表了从最初的娱乐性药物使用向强迫性药物使用的转变。最后,我们发现可卡因的经济需求可以预测一种有前途的药物治疗(催产素)在减轻个体可卡因寻求行为方面的疗效,这表明经济措施可用于快速确定潜在成瘾治疗的临床效用。