In humans, repeated alcohol consumption leads to the development of toleran
ce, manifested as a reduced physiological and behavioral response to a part
icular dose of alcohol. Here we show that adult Drosophila develop toleranc
e to the sedating and motor-impairing effects of ethanol with kinetics of a
cquisition and dissipation that mimic those seen in mammals. Importantly, t
his tolerance is not caused by changes in ethanol absorption or metabolism.
Rather, the development of tolerance requires the functional and structura
l integrity of specific central brain regions. Mutants unable to synthesize
the catecholamine octopamine are also impaired in their ability to develop
tolerance. Taken together, these data show that Drosophila is a suitable m
odel system in which to study the molecular and neuroanatomical bases of et
hanol tolerance.