Stereotypic behavioral responses to free-base cocaine and the development of behavioral sensitization in Drosophila
Stereotypic behavioral responses to free-base cocaine and the development of behavioral sensitization in Drosophila
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DOI：
10.1016/s0960-9822(98)70041-7
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发表时间：
1998-01-15
期刊：
影响因子：
9.2
通讯作者：
Hirsh, J
中科院分区：
文献类型：
--
作者：
McClung, C;Hirsh, J
可卡因滥用是一个巨大的社会和经济问题，近年来受到公众和科学界的广泛关注。啮齿动物和灵长类动物模型已被用于研究可卡因的行为和神经影响。重复间歇剂量的可卡因导致运动活动和刻板行为的逐渐增加，称为“反向耐受”或行为敏化，这可能模拟可卡因成瘾者中发生的行为和神经化学过程[1]。致敏的生物学基础知之甚少。我们报告说，游离碱可卡因管理的挥发性形式的果蝇黑腹果蝇诱导多种反射性运动反应，类似可卡因诱导的行为在啮齿动物。这些行为都是剂量依赖性和性二态性。此外，果蝇对间歇性剂量的可卡因产生了行为敏感性。这些结果表明，导致可卡因诱导的反应和致敏的途径是进化上同意果蝇和高等脊椎动物之间，这种遗传上易于处理的动物可以作为一个新的模型系统，以帮助确定这些过程的生物学机制。
Cocaine abuse is a large social and economic problem that has received much public and scientific attention in recent years. Rodent and primate models have been used to study the behavioral and neurological effects of cocaine. Repeated intermittent doses of cocaine lead to progressive increases in both locomotor activity and stereotyped behaviors known as 'reverse tolerance' or behavioral sensitization, which may model the behavioral and neurochemical processes occurring in cocaine-addicted humans [1]. The biological basis of sensitization is poorly understood. We report that free-base cocaine administered in volatile form to the fruit fly Drosophila melanogaster induces multiple reflexive motor responses that resemble cocaine-induced behaviors in rodents. These behaviors are both dose dependent and sexually dimorphic. Furthermore, Drosophila develops a behavioral sensitization to intermittent doses of cocaine. These results suggest that the pathways leading to cocaine-induced responses and sensitization are evolutionarily consented between Drosophila and higher vertebrates, and that this genetically tractable animal can be used as a new model system to help determine the biological mechanisms underlying these processes.