Neurobiological Study of the Reinforcing Efficacy of Cocaine in Unique Models

可卡因在独特模型中增强功效的神经生物学研究

• 批准号: 7591171
• 负责人: Erik Benjamin Oleson
• 金额: $ 4.12万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-02 至 2011-01-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7591171
• 关键词: Acute; Animal Model; Animals; Biological Neural Networks; Cocaine; Cocaine Dependence; Consumption; Detection; Dopamine; Dose; Exposure to; Human; Individual; Investigation; Laboratories; Measures; Modeling; Motivation; Nature; Neurobiology; Nucleus Accumbens; Procedures; Protocols documentation; Rattus; Recording of previous events; Reinforcement Schedule; Reporting; Scanning; Self Administration; Self-Administered; Training; United States; dopamine transporter; drug of abuse; in vivo; interest; neurochemistry; novel; response; reuptake

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.

描述（由申请人提供）：本申请建议使用新开发的自我管理范式和快速扫描的循环伏安法来表征两个独特的模型。感兴趣的两个模型是长期访问和断点升级模型。长期访问的升级模型反映了可卡因成瘾者中响应和总体消费的升级性质。断点升级模型反映了吸毒者报道可卡因的动机的敏捷。我已经开发并完善量度的自我管理范式以维持可卡因做出反应的最低剂量。在这项建议中，我新开发的自我给药范式将用于衡量动物在训练下在训练后在长期升级，突发点升级或稳定的短路访问控制训练模型下训练后以极低可卡因剂量暴饮暴食的倾向的变化。在暴露于不同的训练历史后，研究动物会反应的最低剂量将提供与这些模型中可卡因自我管理的动机方面有关的新信息。可卡因在断点或长期访问升级模型中可卡因增强功效的基本变化的神经生物学适应性仍然未知。快速扫描的循环大容量允许对极低水平的多巴胺进行高暂时性检测，这是一种神经化学，被很好地接受，与可卡因的急性增强作用有关。我们的实验室报告说，高消耗自我给药训练可能会导致多巴胺转运蛋白的多巴胺再摄取率提高，以响应可卡因。当前的应用进一步建议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。可卡因是美国最令人上瘾，最高度滥用的药物之一。表征动物模型可以帮助我们对可卡因成瘾的神经生物学理解，并可以更好地研究可卡因成瘾者的潜在治疗方法。