Can Tiny Worms Help Unlock the Mystery of Amphetamine Abuse?
A microscopic worm is helping to unlock the mysteries behind the human brain and amphetamine addiction.
Over the past 15 years, Lucia Carvelli, Ph.D., an associate professor of neuroscience at Florida Atlantic University’s Harriet L. Wilkes Honors College, has given the drug to thousands of the worms, which are called Caenorhabditis elegans (C. elegans). She said that the creatures, which are the length of the edge of a dime, can reveal a great deal about how amphetamines affect people.
For Carvelli, the worm’s appeal lies in its simplicity. C. elegans has only 302 neurons; mammals’ brains, by comparison, are almost infinitely more labyrinthine — even mice have billions of neurons and trillions of neural connections. The worm’s elemental structure makes it much easier to study than a mouse or a human. Despite this, Carvelli emphasized that in many crucial ways their nervous systems are quite similar to ours.
“The most important molecules in humans are there in C. elegans,” she said. “We are not so different from these worms.”
This summer, Carvelli was awarded a National Institutes of Health grant for more than $570,000 to study how amphetamine affects the worm’s nervous system. She has two main goals for this research: first, she wants to understand the mechanisms through which amphetamine affects the brain. Despite decades of research, scientists have yet to unravel exactly what the drug does. Scientists have long known that it increases the amount of dopamine in the brain, and that this likely plays a key role in its addictive properties. But Carvelli, who is also a member of Florida Atlantic’s Stiles-Nicholson Brain Institute, said this is only part of the story. Amphetamine is a “dirty” drug, meaning that it affects many different targets in the brain. As a result, its mechanisms almost certainly extend beyond dopamine, something that most people — including many scientists and clinicians — may not realize.
“We still don’t know the mechanism of action,” Carvelli said. “To really prevent or treat addiction, we need to understand how the drug works in the body.”
This is an urgent question. Although amphetamine can be useful — many ADHD medications, such as Adderall, are amphetamine compounds — it can also be deeply harmful. Last year in the United States, nearly 30,000 people died from overdoses involving amphetamine.
Her second goal is to better understand the genes that contribute to the risk of addiction. Some people seem to have a genetic predisposition to amphetamine abuse: of those who use the drug, only about 30 to 40% become addicted. This genetic profile remains largely a mystery. How can she tell which worms may be more prone to abuse? One key indicator is a behavior known as swimming induced paralysis, or Swip. When the worms are placed in amphetamine-infused water, they tend to stop swimming and sink to the bottom (when the amphetamine is removed from the solution, they swim again). Carvelli, who first discovered this phenomenon in C. elegans, suspects that it is food-related. When the worms detect something tasty (generally bacteria), they stop moving so they can eat it. Amphetamine seems to supercharge this behavior, causing them to stop moving more permanently. But not all C. elegans Swip the same way. Some strains require higher doses before they Swip, while others Swip quite quickly. By identifying the genetic differences between strains, Carvelli said she hopes to better elucidate how amphetamine acts on the brain.
She and her team have already identified one gene, lev-1, that appears to make the worms more sensitive to amphetamine. (The same gene is present in humans too.) As she continues her work, Carvelli expects to pinpoint other genes that regulate amphetamine sensitivity. Eventually, this knowledge could be used to develop tests that identify a person’s relative risk of addiction — or to develop medicines that block the effects of, or the craving for, amphetamine.
Carvelli said reaching these goals will likely take years or decades. Fortunately, she loves what she does. She joked that the scientific process —posing questions, doing experiments and evaluating the results — is how she gets her dopamine hit.
“For me, science is like a drug of addiction,” she said. “Luckily it’s a healthy kind of addiction.”