Brain Candy

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Brain Candy

So what does British rock-’n’-roll bad boy Ozzy Osbourne share with the lowly nematode C. elegans?

Well, nothing really, except that this minuscule, transparent worm could clue us in on why Osbourne survived after years of flagrant alcohol and drug abuse.

“Osbourne will be studied by research teams and physicians at the Cambridge, Mass.-based company Knome, which provides whole genome sequencing and interpretation services to researchers and families, to find out if there’s a genetic component to his survival,” said Dr. Lucia Carvelli, a pharmacologist who recently joined Dr. Jonathan Geiger’s team at the University of North Dakota School of Medicine and Health Sciences Department of Pharmacology, Physiology, and Therapeutics.

Carvelli, who grew up in Milan, Italy, is working with C. elegans to detail exactly what amphetamines, cocaine, and other addictive drugs do at the molecular level in the brain.

Her research could also shed light on Parkinson’s disease, a neurodegenerative condition with no known cure, and attention deficit hyperactivity disorder (ADHD), both related to the malfunction of the dopaminergic system, the same system that causes some folks to get hooked on booze, crack, and other addictive drugs.

Carvelli got her PhD at the world-famous Mario Negri Institute of Pharmacological Research, where she developed her intense interest in the chemistry of pleasure-seeking neurons, the little guys that give us a kick when we eat a nice chunk of chocolate ice cream or kiss our favorite person. At the Institute, Carvelli received the Alfredo Leonardi Award as the top PhD student of the year in 1999.

Joining the UND SMHS’ neuroscience research team in March, Carvelli quickly started some microscopic electrical detective work: she probes the molecular basis of drug addiction by systematically testing the electrical energy released when individual neurons release or receive dopamine.

“Basically, I’m researching the mechanism of action in drug addiction, specifically the effect of drugs, such as amphetamine and cocaine, on the dopamine transporter, which is a protein expressed only in the dopaminergic neurons that are localized in specific areas of the brain involved in movement, reward, and memory processes,” said Carvelli with a grand smile, drawing rapidly on a whiteboard to explain the research she’s so passionate about.

“It has important roles in learning and memory, in movement, and many other brain functions, including eating and sex,” she said. “It’s what helps us put pleasurable experiences in our memory and urges us to repeat those experiences. But, Carvelli said, this dopaminergic system is susceptible to tricks.

“Sure, that’s how drugs of addiction work—they trick this system,” she said. “They push some people to repeatedly engage in the pleasurable experience so that they become addicted, say, to eating, drinking, or injecting an addictive drug. You can say that these substances mess up the system. We know now that some people have a genetic predisposition to becoming addicted to certain substances or to addictive behavior—in other words, they cannot control their addictive behavior. That loss of control can lead to behaviors such as chronic overeating.”

With more than 1 billion neurons and more connections than most modern computers, the human brain is still impossibly complex to probe directly, she explained.

“So that’s why I use C. elegans in my research,” Carvelli said. “Specifically, I’m studying how the dopamine transporter (DAT) functions and how it’s implicated in the dopamine-related disorders I mentioned earlier, including ADHD and Parkinson’s but also in bipolar disorder and schizophrenia.”

She’s doing all of this on the green fluorescent-dyed neurons—all eight of them—in the 1-millimeter-long, clear-skinned nematode that is the basic tool of her research, which is supported by a $500,000 grant from the National Institutes of Health (NIH) National Institute on Drug Abuse.

“Right now I’m focusing on the addiction-related effects of the dopaminergic system,” she said. “When we say ‘addiction,’ it could be addictive drug abuse, such as amphetamines and cocaine. But addiction can also include things such as food, so by studying this system, we learn about basic life functions such as eating and sex, functions that are fundamental for life and are regulated by the dopaminergic system.”

“So basically, the body has evolved so that every time you do something that’s essential for life, it’s pleasurable,” she explained. “So you want to repeat that pleasurable activity. The brain memorizes that these are good things, and you learn that you want to do them again. The dopaminergic system is involved in that memorization process that tells us those things are good. The fact that some people are very much in control of themselves and some others are not is very appealing for me to study.”

Before joining the School’s PPT department, Carvelli was a research assistant professor and a research associate in the Department of Pharmacology at Vanderbilt University for nine years. She completed her postdoctoral research at the University of Texas Health Science Center in San Antonio, Texas.

Carvelli is a member of the Society for Neuroscience. She has authored and coauthored numerous articles, and has presented at national and international scientific conferences.

Juan Pedrazza

Editor/Writer, University Relations

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