Hardie Shannon L, Zhang Jing X, Hirsh Jay
Department of Biology and Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia 22903, USA.
Dev Neurobiol. 2007 Sep 1;67(10):1396-405. doi: 10.1002/dneu.20459.
The trace biogenic amines tyramine and octopamine are found in the nervous systems of animals ranging in complexity from nematodes to mammals. In insects such as Drosophila melanogaster, the trace amine octopamine is a well-established neuromodulator that mediates a diverse range of physiological processes, but an independent role for tyramine is less clear. Tyramine is synthesized from tyrosine by the enzyme tyrosine decarboxylase (TDC). We previously reported the identification of two Tdc genes in Drosophila: the peripherally-expressed Tdc1 and the neurally-expressed Tdc2. To further clarify the neural functions of the trace amines in Drosophila, we examined normal and cocaine-induced locomotor activity in flies that lack both neural tyramine and octopamine because of mutation in Tdc2 (Tdc2(RO54)). Tdc2(RO54) flies have dramatically reduced basal locomotor activity levels and are hypersensitive to an initial dose of cocaine. Tdc2-targeted expression of the constitutively active inward rectifying potassium channel Kir2.1 replicates these phenotypes, and Tdc2-driven expression of Tdc1 rescues the phenotypes. However, flies that contain no measurable neural octopamine and an excess of tyramine due to a null mutation in the tyramine beta-hydroxylase gene (TbetaH(nM18)) exhibit normal locomotor activity and cocaine responses in spite of showing female sterility due to loss of octopamine. The ability of elevated levels of neural tyramine in TbetaH(nM18) flies to supplant the role of octopamine in adult locomotor and cocaine-induced behaviors, but not in functions related to female fertility, indicates mechanistic differences in the roles of trace amines in these processes.
痕量生物胺酪胺和章鱼胺存在于从线虫到哺乳动物等不同复杂程度动物的神经系统中。在诸如黑腹果蝇等昆虫中，痕量胺章鱼胺是一种公认的神经调节剂，介导多种生理过程，但酪胺的独立作用尚不清楚。酪胺由酪氨酸脱羧酶（TDC）从酪氨酸合成。我们之前报道了在果蝇中鉴定出两个Tdc基因：在外周表达的Tdc1和在神经中表达的Tdc2。为了进一步阐明果蝇中痕量胺的神经功能，我们检测了由于Tdc2（Tdc2(RO54)）突变而缺乏神经酪胺和章鱼胺的果蝇的正常和可卡因诱导的运动活性。Tdc2(RO54)果蝇的基础运动活性水平显著降低，并且对初始剂量的可卡因高度敏感。组成型活性内向整流钾通道Kir2.1的Tdc2靶向表达复制了这些表型，并且Tdc2驱动的Tdc1表达挽救了这些表型。然而，由于酪胺β-羟化酶基因（TbetaH(nM18)）的无效突变而不含可测量的神经章鱼胺且酪胺过量的果蝇，尽管由于章鱼胺缺失而表现出雌性不育，但仍表现出正常的运动活性和对可卡因的反应。TbetaH(nM18)果蝇中神经酪胺水平升高能够替代章鱼胺在成年运动和可卡因诱导行为中的作用，但不能替代与雌性生育相关的功能，这表明痕量胺在这些过程中的作用存在机制差异。
