Scientists have identified a novel compound that can dramatically block cocaine's rewarding effects and prevent relapse behaviour.
The compound targets an important brain receptor and can be used to treat cocaine addiction, for which no effective medications exist, researchers said.
Researchers from the University at Buffalo found the compound, RO5263397, severely blunted a broad range of cocaine addiction behaviours in animals.
"This is the first systematic study to convincingly show that RO5263397 has the potential to treat cocaine addiction," said Jun-Xu Li, senior author and assistant professor of pharmacology and toxicology in the UB School of Medicine and Biomedical Sciences.
"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 novel 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 said.
The UB research tested this hypothesis by using a newly developed TAAR 1 agonist RO5263397, a drug that stimulates TAAR 1 receptors, in animal models of human cocaine abuse.
"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 blunted 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 behaviour.
"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," Li added.
