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.