Dopamine is a neurotransmitter that seems to have been around from about the time of the very first nerves. Every animal we've looked at, including some that branched off prior to the Cambrian, seems to express the dopamine signaling machinery in its nerves. So you might expect that eliminating dopamine entirely would be a fatal step. But, at least when it comes to everyone's favorite fruit fly, Drosophila melanogaster, that's not the case. Flies that apparently lack dopamine signaling manage to live just as long as their peers. They do, however, end up turning into lethargic masochists.

The authors of the paper describing these results, which will be released this week by PNAS, focused on a gene that performs a key chemical conversion on the dopamine production pathway (it produces a protein called tyrosine hydroxylase). Knocking the gene out in flies is fatal, but not because of anything to do with the nerves. Instead, it's also used to help firm up the fly's cuticle, and its absence there causes death during embryonic development. So the authors figured out a way to eliminate the gene in nerve cells while leaving it fully functional in the skin.

With that arranged, the flies lived. Brain extracts showed extremely low levels of dopamine, but the authors blame that on contamination by a related chemical. Running their tests with slightly different settings eliminated the signal. It's not clear what might be going on to cause this signal, but it's probably fair to say that even if the flies still have a bit of dopamine in their nerves, they certainly don't have anything close to normal levels—the authors claim less than two percent. And despite dopamine's ancient role in the nervous system, they're alive.

However, they're nowhere close to normal. Compared to their normal peers, they were very lethargic, moving relatively little through the course of their normal lives, and not expending the effort to move out of the path of a mild electric current. They spent a lot of their time in the fly equivalent of sleep, even during daylight hours, when they are normally active. Despite the lethargy, however, caffeine was still able to give them a kick start, suggesting that there's an intact activity control that is simply not getting the sorts of cues it needs without dopamine around.

The same sorts of issues showed up when feeding and visual activity were tested. The flies that lacked dopamine ate only about a third as much as their normal peers and weren't interested in sugar water even after having been starved. They were still able to respond to sugar and eat, however, which suggests that the animals' brains still have a feeding capacity that ends up going unused without dopamine. The flies also had normal vision and could use it for spatial orientation, but would no longer move towards light (a phenomenon called phototaxis).

The weirdest effect, however, came when the flies were tested for learned aversion, in which an electric shock is associated with a particular odor. Instead of learning to avoid the shock, however, the dopamine-deficient Drosophila ended up being attracted to the odor, hence the authors' use of the term "masochistic" to describe the flies' behavior.

Part of the surprise here is that they flies could get by without dopamine at all. But it's also remarkable just how specific the deficits they exhibited were. Instead of wiping out entire behavioral systems in these flies, the loss of dopamine only took out a degree of control over them. The other somewhat unexpected result is that most of these effects could be at least partially reversed if the flies were provided dopamine in their food. Many neural systems tend to undergo changes in connections through use, but these results suggest that the remodeling isn't necessary for a significant degree of function.

In mammals, dopamine is generally viewed as controlling the reward system that helps reinforce positive experiences (sometimes to the point of addiction). And it's definitely possible to view a lot of the things that went wrong in these flies as having an insufficient reward system, one that can't motivate them to eat or avoid electric currents. Whether it's sufficient to make them a good model for behavior in mammals, however, will probably have to await a more detailed characterization of these mutants.

PNAS, 2010. DOI: 10.1073/pnas.1010930108 (About DOIs).