Brigham Young University researchers, working with Canadian neuroscientists, have induced drug addiction in lab rats without exposing them to any dope. The experiment sheds fresh light on how opiates and other addictive agents "hijack" the brain's reward circuitry by altering neural receptors as if a switch were flipped, according to the article published Friday in the journal Science .
The study's findings could pave the way for medical interventions to unlock addiction's grip on the brain's "pleasure center," but more needs to be learned, said Scott Steffensen, a BYU neuroscientist who co-authored the study with three of his students and a team University of Toronto researchers.
"We are wired for pleasure," said Steffensen, a professor in the department of psychology. "Drugs overwhelm this system that is under tight regulation. It's a sad spiralling disregulation that takes place."
In other words, addicts lose the capacity to experience pleasure from food, skiing on a powder day, music, a baby's smile, sexual intimacy or any of the countless healthy activities that enhance our lives. Addicts' quest for pleasure fixates on a single chemical, which they believe they need to avoid the agonies of withdrawal, said lead author Hector Vargas-Perez, a neurobiologist in Toronto's department of molecular genetics.
To explore their hypothesis that addiction arises from changes in the brain, the researchers isolated a naturally occurring protein, known as brain-derived neurotrophic factor (BDNF), whose levels increase in the brains of addicts. They injected the protein into a part of the rats' brains called the ventral tegmental area, then recorded changes in their neural circuitry and behavior.
"Rats are a great model for addiction," Steffensen said. "We are wired the same way, especially in the area of pleasure."
Building on Steffensen's past research into alcohol dependency, the Utah team, which included BYU students Micah Hansen, Christine Walton and David Allison, handled physiological observations. The Canadian team conducted the behavioral observations.
After administering single shots of the protein into the rats' brains, the Canadians observed them behaving as if they were hooked on the opiate painkiller morphine. In his lab, Vargas-Perez observed test rats abandoning environments, designed to mimic the textures and smells rats instinctively prefer, to seek a fix. Confronted with an injection choice of saline or morphine, they chose morphine, Vargas-Perez said.
"This protein is very important for cells to survive. When you inject the animal, now it causes excitation in neurons. The neurons change their function," he said. "Now we know this mechanism is important. It is the key to changing the system of reward to another one."
Lots of research targets BDNF, not only because of its role in addiction, but because it plays a crucial role in cell survival and brain development, said Glen Hanson, a professor of pharmacology at the University of Utah.
"Its job isn't just to create drug addicts. It's crucial to all sorts of neurotrophic functions," Hanson said, noting that addiction therapy based on blocking BDNG would carry negative side effects.
"It seems to be important to synaptogenesis. That's a fancy way of talking about how brain cells connect," he said. "It applies to learning in general. The motor pathways associated with the behavior become more predominant. That's how you can learn to dribble a basketball without thinking about it. Addiction is kind of the same way."
According to the BYU researchers, BDNF was the agent triggering fundamental changes in how the rats' pleasure-associated neurons are stimulated.
"When insults like drug abuse happen, this factor leads to a switch in these neurons from being dormant to being excitable," Steffensen said. "The neurons undergo a molecular switch, changing from non-dependency to dependency."
The study opens new directions for addiction research, but a medical "cure" for addiction depends on figuring out how BDNF affects neurons.
"What was the role of this protein in mediating that event? Is it changing the molecular dynamic of these neurons?" Steffensen asked. "In our case, the factor switched the neurons from being inhibited to being excited. We still don't know what the molecular substrate is in these neurons that has changed in response to the BDNF."
