Oleson Erik B, Roberts David C S
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Neuropsychopharmacology. 2009 Feb;34(3):796-804. doi: 10.1038/npp.2008.195. Epub 2008 Oct 29.
Various self-administration procedures are being developed to model specific aspects of the addiction process. For example, 'increased cocaine intake over time' has been modeled by providing long access (LgA) to cocaine during daily self-administration sessions under a fixed-ratio (FR1) reinforcement schedule. In addition, 'increased time and energy devoted to acquire cocaine' has been modeled by providing access to cocaine during daily self-administration sessions under a progressive-ratio (PR) schedule. To investigate the distinctiveness of these models, the behavioral economics variables of consumption and price were applied to cocaine self-administration data. To assess changes in consumption and price, cocaine self-administration was tested across a descending series of doses (0.237-0.001 mg per injection) under an FR1 reinforcement schedule to measure drug intake in the high dose range and thresholds in the low range. Cocaine consumption remained relatively stable across doses until a threshold was reached, at which maximal responding was observed. It was found that a history of LgA training produced an increase in cocaine consumption; whereas a history of PR training produced an increase in the maximal price (P(max)) expended for cocaine. Importantly, the concepts of consumption and price were found to be dissociable. That is, LgA training produced an increase in consumption but a decrease in P(max), whereas PR training produced an increase in P(max) without increasing consumption. These results suggest that distinct aspects of the addiction process can be parsed using self-administration models, thereby facilitating the investigation of specific neurobiological adaptations that occur through the addiction process.
目前正在开发各种自我给药程序,以模拟成瘾过程的特定方面。例如,“随着时间的推移可卡因摄入量增加”已通过在固定比率(FR1)强化时间表下的每日自我给药过程中提供长时间获取(LgA)可卡因来模拟。此外,“投入获取可卡因的时间和精力增加”已通过在累进比率(PR)时间表下的每日自我给药过程中提供获取可卡因的机会来模拟。为了研究这些模型的独特性,将消费和价格的行为经济学变量应用于可卡因自我给药数据。为了评估消费和价格的变化,在FR1强化时间表下,对一系列递减剂量(每次注射0.237 - 0.001毫克)的可卡因自我给药进行测试,以测量高剂量范围内的药物摄入量和低剂量范围内的阈值。在达到阈值之前,可卡因消费量在不同剂量下保持相对稳定,此时观察到最大反应。研究发现,LgA训练史会导致可卡因消费量增加;而PR训练史会导致为可卡因支付的最大价格(P(max))增加。重要的是,发现消费和价格的概念是可分离的。也就是说,LgA训练导致消费量增加但P(max)降低,而PR训练导致P(max)增加但消费量不增加。这些结果表明,可以使用自我给药模型来剖析成瘾过程的不同方面,从而便于研究成瘾过程中发生的特定神经生物学适应。