Researchers at the University of Buffalo have been testing a novel compound that could be the first substance to successfully treat cocaine addiction. During animal testing, the compound RO5263397 appeared to block the desire for cocaine, helping rats kick the habit and also helping to keep them from relapsing.
Despite many years of research, science is still searching for an effective compound to treat the debilitating and sometimes deadly problem of cocaine addiction. This newest study also included collaborators from the College of Charleston and the Research Triangle Institute, and was funded by the National Institutes of Health.
The new study was published as a preview article in the online journal Neuropsychopharmacology. The Buffalo researchers, led by senior author Jun-Xi Li, believe that RO5263397 works by stimulating a protein molecule known as trace amine associated receptor 1, or TAAR 1. TAAR 1 is similar to dopamine, which is the chemical that activates the pleasure centers of the brain during cocaine use and gives users a feeling of euphoria.
This feeling of pleasure and euphoria derived from cocaine is the primary driving force behind cocaine addiction. Without those feelings, the addictive loop in which cocaine users get trapped—during which the brain becomes dependent on the high levels of dopamine for normal functioning—never gets going.
TAAR 1 has been found to have a strong limiting effect on dopamine activity in the brain. Li and his fellow researchers speculated that compounds that could stimulate TAAR 1 would disrupt the mechanism that leads to cocaine addiction. The newly developed RO5263397 is one such compound, so researchers put it to the test treating cocaine addiction in rats.
Treating Addiction and Preventing Relapse
During the laboratory experiments, RO5263397 produced strong results when it came to treating cocaine addiction in rats, and also in keeping the rats from relapsing.
The rats’ desire for cocaine was measured by their persistence in staying at or returning to the place where cocaine was administered. This effect is known as conditioned place preference. The rats who were treated with RO5263397 no longer seemed to associate cocaine with pleasure and desirability, and showed significantly less desire to return to or cling to the physical location where cocaine was given. When rats had to work in order to receive a cocaine injection, those treated with RO5263397 also showed significantly less motivation to work and overcome obstacles in order to get cocaine.
One of the biggest challenges in treating cocaine addiction is the frequency with which addicts relapse after a period of sobriety. RO5263397 also showed promising results when it came to keeping the cocaine-addicted rats from returning to their old habits. When these rats were reintroduced to cocaine seven days after their last dose of the drug, or reintroduced to the physical environment where they had used cocaine, they did not resume cocaine-related behaviors.
The study tried several approaches to administering RO5263397 in order to determine which, if any, would have an effect on cocaine use. They found that acute treatment with RO5263397 (single large doses) did not have an observable effect on the cocaine-addicted rats. However, daily doses of RO5263397 showed significant results after approximately seven days.
Li and his fellow researchers plan to continue their studies of RO5263397. Eventually, the results seen in the laboratory will need to be replicated in human trials. Nevertheless, the positive results for cocaine-addicted rats are very promising, because the dopamine pathways in rats that RO5263397 was able to disrupt are very similar to those in humans.
For the immediate future, the major focus for Li’s team will be the continued study of RO5263397’s ability to curb relapse in recovering cocaine users.