Neurobiological Study of the Reinforcing Efficacy of Cocaine in Unique Models

描述（由申请人提供）：本申请提出使用新开发的自我给药范例和快速扫描循环伏安法来表征两种独特的模型。两个感兴趣的模型是长期访问和断点升级模型。长期使用升级模型反映了可卡因成瘾者中观察到的反应和总体消费的升级性质。断点递增模型反映了成瘾者报告的可卡因动机的增加。我开发和完善的自我管理模式可以测量维持可卡因反应的最低可能剂量。在这个提议中，我新开发的自我管理范式将被用来测量动物的倾向，以极低的可卡因剂量下的长期访问升级，断点升级，或稳定的短期访问控制训练模型下的训练后狂欢的变化。调查的最低剂量，动物将响应暴露于不同的训练历史后，将提供新的信息有关的动机方面的可卡因自我管理，在这些模型。在断点或长期访问升级模型中，可卡因的强化功效变化的神经生物学适应仍然未知。快速扫描循环容积允许高时间检测极低水平的多巴胺，这是一种神经化学物质，被广泛接受为参与可卡因的急性强化作用。我们的实验室报告说，高消费自我管理培训可以导致增加率的多巴胺转运蛋白的多巴胺再摄取反应可卡因。本申请进一步提出使用快速扫描循环伏安法，以研究在体内可卡因成瘾的独特模型中多巴胺再摄取中可能发生的变化。可卡因是美国最容易上瘾和滥用的药物之一。描述动物模型有助于我们对可卡因成瘾的神经生物学理解，并将有助于更好地研究可卡因成瘾者的潜在治疗方法。

DESCRIPTION (provided by applicant): This application proposes to use a newly developed self-administration paradigm and fast-scan cyclic voltammetry to characterize two unique models. The two models of interest are the long-access and the break-point escalation models. The long-access escalation model reflects the escalating nature of responding and overall consumption observed in cocaine addicts. The break-point escalation model reflects the incease in motivation to take cocaine reported by addicts. The self-administration paradigm that I have developed and refined measures the lowest possible dose that will maintain cocaine responding. In this proposal, my newly developed self-administration paradigm will be used to measure changes in an animal's propensity to binge at extremely low cocaine doses following training under either the long-access escalation, break-point escalation, or a stable short-access control training model. Investigating the lowest dose for which an animal will respond following exposure to different training histories will provide novel information pertaining to the motivational aspects of cocaine self-administration in these models. The neurobiological adaptations underlying changes in the reinforcing efficacy of cocaine in either the breakpoint or the long-access escalation model remains unknown. Fast-scan cyclic volumetric allows for the high-temporal detection of extremely low levels of dopamine, which is a neurochemical that is well-accepted to be involved in the acute reinforcing effects of cocaine. Our laboratory has reported that high consumption self-administration training can result in an increased rate of dopamine reuptake at the dopamine transporter in response to cocaine. The current application further proposes to use fast scan cyclic voltammetry in order to investigate changes that may occur in dopamine reuptake in the unique models of cocaine addiction in vivo. Cocaine is one of the most addictive and highly abused drugs in the United States. Characterizing animal models can help in our neurobiological understanding of cocaine addiction, and will enable a better investigation of potential treatments for cocaine addicts.