Torres G, Horowitz J M
Department of Psychology, State University of New York at Buffalo, 14260, USA.
Synapse. 1998 Jun;29(2):148-61. doi: 10.1002/(SICI)1098-2396(199806)29:2<148::AID-SYN6>3.0.CO;2-7.
The use of Drosophila as a model to study the behavioral consequences of stimulant drugs was analyzed in an active preparation of decapitated Drosophila. Application of cocaine and cocaethylene to discrete nerve cord cells regulating motor programs of behavior produced striking patterns of behavioral activity in a concentration-related manner. In general, intense circling behavior and significant wing buzzing activity were distinguishable behavioral markers in flies treated with mM concentrations of cocaine or cocaethylene. The significant changes in motor behavior induced by stimulant drugs in decapitated flies were not reproduced by the application of apomorphine, a direct dopamine (DA) agonist, or octopamine, a naturally occurring transmitter in arthropods. Because both cocaine and cocaethylene interfere with DA reuptake in mammals, we characterized the role of DA receptors mediating increased stereotypy and motor behavior in flies. Coadministration of SCH-23390, a specific D1 receptor antagonist, significantly attenuated the behavior-activating properties of cocaine and cocaethylene in this active experimental preparation. Therefore, the receptor protein mediating the behavioral responses to stimulant drugs in Drosophila is pharmacologically similar to the mammalian D1 subtype. In rats, cocaine- and cocaethylene-induced behavioral activity is complex, with increasing evidence that the D1 receptor interacts significantly with N-methyl-D-aspartate (NMDA) receptor pathways to produce an altered behavioral phenotype. To further characterize additional receptor subtypes targeted by the actions of cocaine and cocaethylene, we pretreated flies with MK-801 and dextromethorphan. Both of these drugs are potent, selective noncompetitive NMDA receptor antagonists. Interestingly, MK-801 and dextromethorphan profoundly reduced the behavior-activating properties of cocaine and cocaethylene in Drosophila. Therefore, as in rats, the NMDA (and D1) receptor pathways in this arthropod represent obligatory targets for the behavioral effects of stimulant drugs.
在一项对断头果蝇的活性制备实验中，分析了将果蝇用作研究兴奋剂药物行为后果的模型。将可卡因和古柯乙烯应用于调节行为运动程序的离散神经索细胞，以浓度相关的方式产生了显著的行为活动模式。一般来说，在用毫摩尔浓度的可卡因或古柯乙烯处理的果蝇中，强烈的转圈行为和明显的翅膀嗡嗡声活动是可区分的行为标记。在用阿扑吗啡（一种直接的多巴胺（DA）激动剂）或章鱼胺（节肢动物中天然存在的递质）处理时，并未重现兴奋剂药物在断头果蝇中诱导的运动行为的显著变化。由于可卡因和古柯乙烯在哺乳动物中都会干扰多巴胺再摄取，我们对介导果蝇刻板行为增加和运动行为的多巴胺受体的作用进行了表征。特异性D1受体拮抗剂SCH - 23390的共同给药显著减弱了可卡因和古柯乙烯在这个活性实验制剂中的行为激活特性。因此，介导果蝇对兴奋剂药物行为反应的受体蛋白在药理学上与哺乳动物的D1亚型相似。在大鼠中，可卡因和古柯乙烯诱导的行为活动很复杂，越来越多的证据表明D1受体与N - 甲基 - D - 天冬氨酸（NMDA）受体途径有显著相互作用，从而产生改变的行为表型。为了进一步表征可卡因和古柯乙烯作用所靶向的其他受体亚型，我们用MK - 801和右美沙芬预处理果蝇。这两种药物都是强效、选择性的非竞争性NMDA受体拮抗剂。有趣的是，MK - 801和右美沙芬显著降低了可卡因和古柯乙烯在果蝇中的行为激活特性。因此，与大鼠一样，这种节肢动物中的NMDA（和D1）受体途径是兴奋剂药物行为效应的必需靶点。
