Flies on meth burn through sugar

A famous antidrug ad compares the brain on drugs to a frying egg. Now, a new study gives a broad look at how methamphetamine might scramble the entire body.

In one of the broadest surveys yet, U.S. researchers have illustrated the many genetic and cellular impacts of meth exposure in fruit flies. In addition to likely wreaking havoc on muscles and sperm, the drug seems to kick fly sugar metabolism into overdrive, the group reports online April 20 in PLoS ONE.

“One tends to think of methamphetamine as being a drug of abuse largely for fairly advanced organisms,” says Desmond Smith, a geneticist at UCLA who was not involved in this study. “It was quite nifty to try and look at what’s happening in the humble fly.”

Though flies and people are very different beasts, meth appears to tweak some of the same basic biochemical networks in both, says Barry Pittendrigh, a coauthor of the new report. And while the fruit fly Drosophila melanogaster may be humble, it’s also one of the best explored organisms in science. Using fruit flies, scientists can probe meth’s toll not just on genes but also on big molecules such as proteins and on little molecules like sugars with ease. That makes this iconic bug a good window on a uniquely human addiction.

Meth batters cells throughout the fly’s body. “It’s a really horrible compound,” says Pittendrigh, a molecular entomologist at the University of Illinois at Urbana-Champaign. The drug seems to kick off muscle degradation, disrupt sperm production and even speed up the aging process in a host of cells.

Studies in mice and humans have similarly documented the drug’s devastating impacts on the heart, fertility and on cell aging. The new study, however, also reveals how meth can act like a back-alley strangler.

When cells can’t get enough oxygen, such as during exercise, they break down sugar molecules like a chop shop for stolen cars — quickly and messily. Cells exposed to meth seem to go into this same chop-shop mode, says study coauthor Manfredo Seufferheld, also at Illinois. Why isn’t clear — the drug could somehow be cutting cells or parts of cells off from the body’s oxygen supply. But meth may also switch on a few key genes that convince cells to metabolize sugar as though they were suffocating even when oxygen is plentiful. Either way, such inefficient sugar crunching could leave cells with an insatiable appetite for more carbohydrates. (Curiously, many cancer cells adopt a similar gluttonous lifestyle.)

This change in sugar metabolism may help explain why speed addicts develop a pronounced sweet tooth. “They consume absolutely every gram of sugar that they have available,” Seufferheld says. Feeding that sweet tooth may slow meth’s ravages, he suggests. Drug-addicted flies with extra sugar in their diets survived longer than their sugar-deprived compatriots, the team discovered.

Knowing how meth works isn’t trivial, says Jean Lud Cadet, a molecular neurobiologist who works in Baltimore at the Intramural Research Program of the National Institute on Drug Abuse. He’d eventually like to develop compounds that block speed’s activity in the brain, giving drug addicts some extra protection and maybe saving that egg from the frying pan.