Published May 1, 2014
A novel compound severely blunts a host of cocaine addiction behaviors, including relapse behavior, according to a University at Buffalo animal study that holds promise for a groundbreaking treatment.
“This is the first systematic study to convincingly show that the newly developed RO5263397 compound has the potential to treat cocaine addiction,” says senior author Jun-Xu Li, MD, PhD, assistant professor of pharmacology and toxicology.
The findings are especially important since no effective medications currently exist to treat this addiction, despite many years of research, Li says.
Results have been published as an online preview article in Neuropsychopharmacology.
RO5263397 targets and stimulates the trace amine-associated receptor 1 (TAAR 1), a novel brain receptor expressed in key drug reward and addiction regions of the brain.
Using animal models of human cocaine abuse, “our research shows that TAAR 1 holds great promise as a novel drug target for the development of novel medications for cocaine addiction,” says Li.
Anatomically and neurochemically, TAAR 1 is closely related to dopamine — one of the key molecules in the brain that contributes to cocaine addiction, Li explains.
This receptor is thought to be a “brake” on dopamine activity, Li says. Therefore, “drugs that stimulate TAAR 1 may be able to counteract cocaine addiction.”
The researchers tested the rewarding effects of cocaine in part through conditioned place preference, or assessing an animal’s persistence in returning to — or staying at — a physical location where the drug is given.
Li’s study shows that RO5263397 dramatically blocks rewarding effects.
“When we give the rats RO5263397, they no longer perceive cocaine as rewarding, suggesting that the primary effect that drives cocaine addiction in humans has been blunted,” says Li.
The compound also blunts cocaine relapse in animals, the study shows.
“Cocaine users often stay clean for some time, but may relapse when they re-experience cocaine or hang out in the old cocaine-use environments,” Li explains.
“We found that RO5263397 markedly blocks the effect of cocaine or cocaine-related cues for priming relapse behavior.”
Additionally, when the researchers measured how hard the animals were willing to work for a cocaine injection, they found that RO5263397 reduces motivation.
“This compound makes rats less willing to work for cocaine, which leads to decreased cocaine use,” he says.
Li and his team plan to continue studying RO5263397, especially its effectiveness and mechanisms involved in curbing relapse to cocaine addiction.
In addition to Li, co-authors from the Department of Pharmacology and Toxicology are:
Other coauthors are from the College of Charleston and the Research Triangle Institute.
The research was funded by the National Institutes of Health.