Fruit flies can help us understand cocaine addiction

For the first time, scientists have created genetically modified fruit flies that can develop an addiction to cocaine.

Given the option, these flies will self-administer the drug. This new model may offer a faster way to develop therapies aimed at preventing and treating cocaine use disorder, a serious condition affecting about 1.5 million people in the United States.

Cocaine use disorder has a strong hereditary component. Many genes play a role in addiction risk, but finding the best targets for treatment has been challenging.

With this new fruit fly model, researchers believe they can study the biology of addiction in a simpler system and speed up the search for better therapies.

Studying flies and cocaine addiction

Flies and humans respond to cocaine in strikingly similar ways. “At low doses, they start running around, just like people,” said Dr. Adrian Rothenfluh, associate professor of psychiatry at the University of Utah. “At very high doses, they get incapacitated, which is also true in people.”

When it comes to addiction, humans and flies share more than just behavior. Flies carry about 75% of the human genes known to be involved in diseases. They have already helped scientists uncover the basic biology behind other forms of substance dependence.

Because fruit flies grow quickly and are easy to manipulate genetically, they could become a key tool for studying cocaine addiction. But there was a major problem standing in the way.

“Flies do not like cocaine one bit,” noted Dr. Rothenfluh. When given a choice, flies always preferred sugar water without cocaine, even after prior cocaine exposure. This resistance needed to be overcome to build an effective addiction model.

Bitter taste blocks cocaine

The breakthrough came when the research team, led by Dr. Travis Philyaw, looked more closely at the flies’ sense of taste.

“Insects are evolutionarily primed to avoid plant toxins, and cocaine is a plant toxin,” said Dr. Philyaw, who is now a research scientist at the University of Washington.

“They have taste receptors on their ‘arms’ – their tarsal segments – so they can put their hand in something before it goes in their mouth and decide, ‘I’m not going to touch that.'”

By studying the sensory nerves in the flies’ legs, the researchers found that cocaine strongly activates the bitter-sensing taste receptors. To see what would happen without this barrier, they muted the bitter-sensing nerves.

Once the experts blocked the flies’ ability to taste bitter substances, something remarkable occurred.

The flies started choosing the cocaine-laced sugar water over the plain version. They would only do so at low cocaine concentrations, but they developed this preference quickly – within just 16 hours of first exposure.

Mechanisms of cocaine choice

Now that flies can model cocaine addiction, researchers have a powerful tool to study the genes involved.

Fruit flies offer the advantage of speed. Scientists can test hundreds of genes in a fraction of the time it would take in more complex animals.

“We can scale research so quickly in flies,” noted Dr. Philyaw. “We can identify risk genes that might be difficult to uncover in more complex organisms, and then we pass that information to researchers who work with mammalian models.”

“Then, they’re able to uncover treatment targets that facilitate the jump from studying animal behavior to developing human therapeutics.”

Dr. Rothenfluh sees this model as an important step forward. “We can really start to understand the mechanisms of cocaine choice,” he said. “The more you understand about the mechanism, the more you have a chance to find a therapeutic that might act on that mechanism.”

Flies sheds light on human minds

Beyond addiction studies, this research highlights the value of basic science. Understanding the fly brain, simple as it is, can lead to insights about the human mind.

“Just trying to understand the simple little fly brain can give us insights that you cannot anticipate,” Rothenfluh said. “Basic science is important, and you never know what exciting things you might find that turn out to be impactful for understanding the human condition.”

The full study was published in the journal JNeurosci.

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