Published September 19, 2014
Research by David Dietz, PhD, has the potential to identify novel therapies for treating addiction to cocaine and other psychostimulants, for which no effective drug therapy exists.
With a five-year, $2 million grant from the National Institute on Drug Abuse, Dietz will study short- and long-term neurobiological changes in the brain that are induced by addiction.
Addiction takes hold because the brain becomes rewired, explains Dietz, principal investigator and assistant professor of pharmacology and toxicology.
An addict’s brain undergoes dramatic and profound changes, known as neuroplasticity, while being exposed to cocaine, he says.
Neuroplasticity includes cellular changes that, in turn, control changes in the shape of neurons and the number of connections they have with other neurons, ultimately causing changes in the addict’s behavior, he notes.
“These changes persist and become permanent,” Dietz emphasizes. That’s why “after staying clean for a month or a year, an addict will — seemingly without reason — start using drugs again.”
“The question is, how can we interfere with those changes?” he asks. “How can we either prevent the rewiring in the addicted state or somehow reverse it?”
The in vivo study is the first to focus on transforming growth factor-beta (TGF-beta) signaling, which may be a master regulator of pathways previously discovered to be important in addiction, Dietz says.
According to Dietz, TGF-beta controls changes in two ways: by directly regulating mechanisms that alter the structural reorganization of neurons and by controlling long-term, transcriptional effects of genes that maintain these adaptations.
This long-term effect sustains the rewiring in the brain and makes it permanent, he explains.
A key aspect of the study, “Cocaine-Induced Neuroplasticity: A New Role for TGF Beta Signaling,” involves learning how the brain changes at different time-points following abstinence from drugs.
“You may need to treat a person who has been in withdrawal for one day very differently from someone who has been in withdrawal for one month or even longer,” says Dietz.