Cocaine-induced behaviors in larval zebrafish

描述（由申请方提供）：拟定研究的目的是确定斑马鱼中可卡因给药和可卡因戒断的行为相关性。 这一建议的中心假设是，在较低的脊椎动物的药物奖励和药物成瘾的神经生物学机制是类似的哺乳动物和调查他们在斑马鱼，较低的昼夜脊椎动物具有良好的特征遗传学，将导致更好地了解成瘾性疾病和更有效的治疗策略的发展。这需要详细描述斑马鱼对可卡因的物种特异性反应，并评价适用于大规模筛选程序的方法。 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性位置偏好; ii）对斑马鱼幼鱼的游泳和转向模式进行高速数字成像。 这些技术将使我们能够：a）表征可卡因处理和可卡因戒断对斑马鱼幼体的运动活动及其昼夜节律模式的影响; B）确定斑马鱼幼体是否对可卡因产生行为敏化; c）确定斑马鱼幼体是否对可卡因产生位置偏好; d）表征可卡因处理和可卡因戒断对特定运动模式的影响，例如，e）确定褪黑激素处理是否可以调节可卡因诱导的斑马鱼行为变化。 详细描述斑马鱼幼鱼对可卡因的行为反应将为深入研究药物成瘾的分子和神经机制奠定必要的基础，使用多种突变表型和转基因斑马鱼。 这可以促进我们对成瘾物质的神经元和细胞内靶点以及易受药物成瘾影响的遗传基础的理解。

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.