Controlling dopamine levels poses potential for treating diseases, drug abuse

By Amanda Scurry
The workings of the human brain are so complex that it is still a frontier in the scientific world.  That is exactly why Dr. Roxanne Vaughan, associate professor of biochemistry and molecular biology at the University of North Dakota School of Medicine and Health Sciences, chose to study it 16 years ago.
 
“I love working with neurotransmitter transporters,” explains Vaughan.  “They are parts of the brain that are not well understood, so there is an opportunity to make a lot of discoveries.”

Vaughan came to UND eight years ago from the National Institute on Drug Abuse (NIDA), a division of the National Institutes of Health based in Baltimore, Md. 

With two grants totaling nearly $3 million from NIDA, Vaughan and her team of researchers at UND are investigating how the brain enjoys itself. 

Too much of a good thing
Dopamine is a chemical produced by the brain that allows you to feel good, whether it is from the occasional chocolate indulgence or drugs like cocaine. 
The dopamine transporter, or DAT for short, is a protein in the brain that regulates the flow of dopamine.  The DATs work as dimmer switches for dopamine, regulating its flow based on the need of the brain.  This process is essential to life.

However, drugs like cocaine bind to the DAT, stopping it from doing its job.  This causes too much dopamine to be present in the brain.  Although dopamine is a natural compound, too much of it in the brain can result in mental illness and psychotic behavior.

Laura Parnas, a doctoral student originally from Santiago Del Estero, Argentina, has spent the past five years working with Vaughan to discover how these drugs bind with DATs in the first place.
 
Parnas came to UND through a foreign exchange program to work on a master’s degree within the Department of Biochemistry and Molecular Biology.  She soon realized she had the knack for it and decided to stay on to pursue her doctorate.
 
“Dr. Vaughan is very generous to us,” remarked Parnas.  “She provides us with so many opportunities to help us learn as scientists.”

If Vaughan and Parnas can discover how elements of cocaine bind to DATs, that could facilitate development of pharmaceuticals to prevent that binding and, hence, the effects of the drug on the brain.
 
Beyond cocaine
Vaughan’s lab is also looking at how the rate of DAT activity is controlled to regulate the levels of dopamine in the brain.  The team is looking at the physiological processes that increase or decrease DAT function, and how these biochemical pathways are affected by drugs. 
However, this research has farther-reaching implications than drug abuse.  Naturally occurring low levels of dopamine have been linked to depression and Parkinson’s disease, while high levels of dopamine are associated with schizophrenia and other mental illnesses. 
 
Once Vaughan’s team discovers how dopamine transport is controlled, treatments may be developed to artificially adjust those processes.  This would benefit people suffering from drug abuse, because it would cause the drugs to lose their ability to create a high, and could also treat mental illness and other diseases, allowing doctors to put dopamine within normal levels for their patients.

On the forefront
Through their groundbreaking research, Vaughan’s team has brought UND to the forefront of the field.
“When we present at meetings, we can really see the impact we are making on a national and international level,” said Parnas, “right here in North Dakota.”
“It is very gratifying that in a small way what we are doing here might help people,” said Vaughan.