A research team from the University of Buffalo claims to have found a compound that targets a key brain receptor to halt a number of cocaine addiction problems including relapse.
The study shows the compound, RO5263397, tones down a host of cocaine addiction behavior. "This is the first systematic study to convincingly show that RO5263397 has the potential to treat cocaine addiction," Jun-Xu Li, MD, PhD, senior author and assistant professor of pharmacology and toxicology in the UB School of Medicine and Biomedical Sciences, said in a press release.
"Our research shows that trace amine associated receptor 1 -- TAAR 1 -- holds great promise as a novel drug target for the development of novel medications for cocaine addiction," he said.
TAAR 1 is a receptor in the brain that gets charged up by the minute amounts of brain chemicals known as trace amines. "Because TAAR 1 anatomically and neurochemically is closely related to dopamine -- one of the key molecules in the brain that contributes to cocaine addiction -- and is thought to be a 'brake' on dopamine activity, drugs that stimulate TAAR 1 may be able to counteract cocaine addiction," Li explained.
For the study, the research team examined this theory by using a newly developed TAAR 1 agonist RO5263397, a drug that excites TAAR 1 receptors, in animal models of cocaine abuse.
In one particular method, what researchers called as conditioned place preference, the team tested the animal's persistence in returning to, or staying at, a physical location where the drug was administered. It was seen as an indicator that the drug has rewarding effects.
The researchers found, RO5263397 dramatically blocked cocaine's rewarding effects.
"When we give the rats RO5263397, they no longer perceive cocaine rewarding, suggesting that the primary effect that drives cocaine addiction in humans has been blunted," said Li.
The compound also markedly dulled cocaine relapse in the animals.
"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," said Li. "We found that RO5263397 markedly blocked the effect of cocaine or cocaine-related cues for priming relapse behavior.
"Also, when we measured how hard the animals are willing to work to get an injection of cocaine, RO5263397 reduced the animals' motivation to get cocaine," said Li. "This compound makes rats less willing to work for cocaine, which led to decreased cocaine use."
According to Li, the study findings are important as despite many years of research, there are no effective medications for treating cocaine addiction.
The UB research was published as an online preview article in 'Neuropsychopharmacology'.
