By combining behavioral, chemical, electrophysiological and genetic approaches we have provided the first direct neuronal evidence of cuticular hydrocarbon sex pheromone processing in an insect. We have also shown that an inhibitory sex pheromone and repulsive gustatory stimuli are processed by the same neurons (The L2 cells corresponding to some Gr66a-Gal4 expressing neurons) and induced similar behavioral responses. For the male fly, there is apparently no difference between the sensation induced by bitter stimuli and that induced by the inhibitory pheromone 7-T.
Given that the two types of substances have little structural similarity–7-T is a straight chain hydrocarbon whereas berberine, caffeine, and quinine are oxygenated, oligocyclic alkaloids–it is unlikely that they are detected by the same receptor molecule. Since multiple types of GR molecules are probably co-expressed in Gr66a-Gal4
expressing labellar taste neurons 
, and the GR66A receptor molecule is involved in the detection of caffeine 
, this suggests that 7-T and perhaps other bitter substances are detected by other, unknown receptor molecule(s). In this case, cross-adaptation would presumably take place through common activation of second-messenger systems or of calcium trafficking 
It is not yet clear how GAL4 alters the activity of Gr66a
expressing neurons. Recent results have shown that GAL4 can have a toxic effect on neurons 
. This could also explain previous findings in which male flies carrying a single copy of a Gal4 transgene targeting taste sensilla showed altered pheromonal responses 
Our findings provide experimental support for Darwin's hypothesis that sexual selection operates on pre-existing structures and behaviors, co-opting them into new functions 
. In the present case, we propose that pre-existing neuronal networks responsible for detecting and responding to bitter substances became able to detect stimuli produced by other males, with the result that these stimuli inhibited male courtship by activating aversive behaviors that were previously solely induced by bitter stimuli. A similar—likely convergent—process may have taken place in vertebrates, when some semiochemicals produced by male mice are detected by specialized receptor molecules in the main olfactory bulb, not in the accessory olfactory system, which had previously been considered to be the sole site of pheromone processing 
. We have shown that identical peripheral neurons are involved in detecting inhibitory pheromones and aversive gustatory stimuli. The next challenge will be to understand how these signals are represented in the fly brain.