Cocaine-induced behaviors in larval zebrafish

可卡因诱导斑马鱼幼虫的行为

• 批准号: 6725309
• 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 2006-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6725309
• 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)：拟议研究的目标是建立斑马鱼服用可卡因和戒除可卡因的行为相关性。这一建议的中心假设是，低等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相似，在斑马鱼中进行研究，将有助于更好地了解成瘾障碍，并开发更有效的治疗策略。斑马鱼是一种具有良好特征的日活动较低的脊椎动物。这需要详细描述斑马鱼对可卡因的特定物种反应，并评估适用于大规模筛查程序的方法学办法。拟议的研究将通过以下方式完成：i)使用数字图像分析系统自动记录斑马鱼的运动活动和条件位置偏好；以及ii)对斑马鱼幼体的游动和转弯模式进行高速数字成像。这些技术将使我们能够：a)鉴定可卡因处理和戒断对斑马鱼幼体运动活动及其昼夜节律的影响；b)确定斑马鱼幼体是否对可卡因产生行为敏感化；c)确定斑马鱼幼体是否对可卡因产生地点偏好；d)表征可卡因处理和戒断对特定运动模式的影响，如游泳和转身；e)确定褪黑素处理是否能调节可卡因诱导斑马鱼行为的变化。对斑马鱼幼体对可卡因的行为反应进行详细的表征，将为利用多种突变表型和转基因斑马鱼深入研究药物成瘾的分子和神经机制奠定必要的基础。这可能会促进我们对成瘾物质的神经元和细胞内靶标以及易受药物成瘾影响的遗传基础的理解。