Rapid dopamine dynamics after repeated cocaine exposure

反复接触可卡因后多巴胺动态快速变化

• 批准号: 7676422
• 负责人: Nii A Addy
• 金额: $ 4.72万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-13 至 2012-04-12
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7676422
• 关键词: Acute; Address; Animal Model; Behavior; Behavioral; Brain; Brain region; Cells; Cocaine; Cocaine Abuse; Cocaine Users; Cues; Dopamine; Euphoria; Event; Feeling; Frequencies; Goals; Human; Hyperactive behavior; Lead; Literature; Mediating; Microdialysis; Neurobiology; Neurons; Nucleus Accumbens; Play; Preparation; Process; Rattus; Research; Role; Scanning; Second Messenger Systems; Self Administration; Signal Transduction; Synaptic plasticity; System; Time; United States; Ventral Tegmental Area; Withdrawal; Work; addiction; behavioral sensitization; cocaine exposure; dopamine transporter; dopaminergic neuron; in vivo; insight; mesolimbic system; neurochemistry; neurotransmitter release; response; second messenger; uptake

DESCRIPTION (provided by applicant): Cocaine abuse in the United States continues to be of concern with an estimated 1 million new cocaine users each year (USHHS, 2006). Cocaine acts to inhibit dopamine transporters in the brain, which in turn increases dopamine availability to produce feelings of euphoria. In addition, these dopamine effects lead to several behavioral changes including locomotor hyperactivity, cocaine seeking behavior and cocaine self- administration. While the microdialysis literature has illustrated a progressive, or sensitized, increase in dopamine levels and locomotor hyperactivity with repeated cocaine exposure, these studies have not been extended to include rapid dopamine dynamics. Fast scan cyclic voltammetry (FSCV), which can detect dopamine fluctuations on a sub-second time scale, provides an ideal means for such analyses. Further, an understanding of these rapid dopamine dynamics is important as they have been observed in response to acute cocaine administration and may play a role in behavioral responses to cocaine. The work proposed here will use in vivo FSCV to 1) characterize real time dopamine release in the nucleus accumbens core and shell after acute and repeated cocaine exposure and 2) determine the role of rapid dopamine release in the nucleus accumbens in cocaine-mediated locomotor sensitization. Specifically, in vivo FSCV recordings will be performed in rats after different periods of cocaine administration and withdrawal in order to fully characterize these dopaminergic responses. ' r The overall goal of this research is to determine how long term cocaine exposure alters dopamine effects in the brain to infleunce behavior. Such work will provide valuable insight as to how such processes may contribute to cocaine abuse in humans.

描述（由申请人提供）：美国滥用可卡因滥用，每年估计有100万新可卡因用户（USHHS，2006年）继续关注。可卡因的作用是抑制大脑中的多巴胺转运蛋白，进而增加多巴胺的可用性以产生欣快的感觉。此外，这些多巴胺作用导致了几种行为变化，包括运动多动症，可卡因寻求行为和可卡因自我给药。尽管微透析文献说明了多巴胺水平和运动过度活跃的渐进性或敏感性，并反复接触可卡因，但这些研究尚未扩展到包括快速的多巴胺动力学。快速扫描循环伏安法（FSCV），可以在次秒时间尺度上检测多巴胺波动，为此类分析提供了理想的手段。此外，对这些快速多巴胺动力学的理解非常重要，因为它们响应急性可卡因给药而被观察到，并且可能在对可卡因的行为反应中起作用。此处提出的工作将使用体内FSCV至1）表征急性和重复可卡因暴露后的伏伏核和外壳中的实时多巴胺释放，以及2）确定快速多巴胺释放在可卡因介导的显影剂刺激中的快速多巴胺释放的作用。具体而言，在不同的可卡因给药和戒断后，将在大鼠中进行体内FSCV记录，以充分表征这些多巴胺能反应。这项研究的总体目标是确定可卡因的长期暴露会改变大脑中多巴胺的影响，从而改变了反伦斯行为。此类工作将为此类过程如何促进人类可卡因滥用行为提供宝贵的见解。