A new compound that targets an important brain receptor dramatically blocks cocaine’s reward effect and significantly blunts relapse, new research with rats shows.
Jun-Xu Li, assistant professor of pharmacology and toxicology at the University at Buffalo, says the study is one of the first to show convincingly that the drug (known as RO5263397) has the potential to treat cocaine addiction.
The findings are especially important, Li says, since despite many years of research, there are no effective medications for treating cocaine addiction.
“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.”
TAAR 1 is a receptor in the brain that is activated by minute amounts of brain chemicals called trace amines. The compound targets TAAR 1, which is expressed in key drug reward and addiction regions of the brain.
“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 says.
May prevent relapse
One of the ways researchers test the rewarding effects of the drug in animals is called conditioned place preference. In this type of test, the animal’s persistence in returning to, or staying at, a physical location where the drug is given indicates the drug has 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,” says Li.
The results also suggest the drug made it less likely for the rats to relapse.
“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. We found that RO5263397 markedly blocked the effect of cocaine or cocaine-related cues for priming relapse behavior,” Li says.
“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. This compound makes rats less willing to work for cocaine, which led to decreased cocaine use.”
Other researchers from University at Buffalo, from College of Charleston, and from the Research Triangle Institute contributed to the study.
The National Institutes of Health funded the research.
Source: University at Buffalo