Cocaine-induced behaviors in larval zebrafish

可卡因诱导斑马鱼幼虫的行为

• 批准号: 6882078
• 负责人: IRINA V. ZHDANOVA
• 金额: $ 24.23万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6882078
• 关键词: behavior test; behavioral /social science research tag; behavioral habituation /sensitization; chordate locomotion; circadian rhythms; cocaine; digital imaging; diving /swimming; drug addiction; drug withdrawal; embryo /fetus toxicology; ethology; genetically modified animals; immature animal; larva; melatonin; micromanipulator; phenotype; reinforcer; statistics /biometry; substance abuse related behavior; zebrafish

DESCRIPTION (provided by applicant): The goal of the proposed studies is to establish the behavioral correlates of cocaine administration and cocaine withdrawal in zebrafish. The central hypothesis of this proposal is that neurobiological mechanisms of drug reward and drug addiction in lower vertebrates are similar to those in mammals and that investigating them in zebrafish, a lower diurnal vertebrate with well-characterized genetics, would lead to a better understanding of addictive disorders and the development of more effective treatment strategies. This requires a detailed characterization of species-specific responses to cocaine in zebrafish and the evaluation of methodological approaches applicable to large-scale screening procedures. The proposed studies will be accomplished by conducting: i) automatic recordings of zebrafish locomotor activity and conditioned place preference, using digital image analysis system; and ii) high-speed digital imaging of swimming and turning patterns in larval zebrafish. These techniques will allow us to: a) Characterize the effects of cocaine treatment and cocaine withdrawal on locomotor activity and its circadian pattern in larval zebrafish; b) Establish whether zebrafish larvae develops behavioral sensitization to cocaine; c) Determine whether zebrafish larvae develops place preference to cocaine; d) Characterize the effects of cocaine treatment and cocaine withdrawal on specific locomotor patterns, e.g., swimming and turning; e) Determine whether melatonin treatment can modulate cocaine-induced changes in zebrafish behavior. A detailed characterization of the behavioral responses to cocaine in larval zebrafish would create a necessary foundation for intensive studies on the molecular and neuronal mechanisms of drug addiction, using multiple mutant phenotypes and transgenic zebrafish available. This could advance our understanding of the neuronal and intracellular targets of addictive substances and the genetic bases of vulnerability to drug addiction.

描述（由申请人提供）：拟议的研究的目的是建立可卡因给药和可卡因在斑马鱼中的行为相关性。 该提议的中心假设是，在较低脊椎动物中，药物奖励和药物成瘾的神经生物学机制与哺乳动物中的神经生物学机制相似，并且在斑马鱼中进行了研究，斑马鱼是一种较低的昼夜脊椎动物，具有良好的遗传学特征性的遗传学，可以更好地理解成瘾性的疾病，并具有更多有效治疗策略的发展。这需要对斑马鱼中对可卡因的特定物种反应以及适用于大规模筛查程序的方法学方法的详细表征。 拟议的研究将通过进行：i）使用数字图像分析系统进行：）斑马鱼运动活动和条件地位偏好的自动记录； ii）在幼虫斑马鱼中游泳和转弯模式的高速数字成像。 这些技术将使我们能够：a）表征可卡因治疗和可卡因戒断对运动运动及其在幼虫斑马鱼中的昼夜节律模式的影响； b）确定斑马鱼幼虫是否发展出对可卡因的行为敏感； c）确定斑马鱼幼虫是否发展出对可卡因的偏好； d）表征可卡因治疗和可卡因戒断对特定运动模式的影响，例如游泳和转弯； e）确定褪黑激素治疗是否可以调节可卡因诱导的斑马鱼行为变化。 使用多重突变体表型和转基因斑马鱼可用，对幼虫斑马鱼中可卡因的行为反应的详细表征将为对药物成瘾的分子和神经元机制的深入研究创造必要的基础。 这可以提高我们对成瘾性物质的神经元和细胞内靶标以及对吸毒成瘾的脆弱性的遗传基础的理解。