Tuesday, Jul 29, 2014
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Compound may be able to curb desire for cocaine


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A compound being tested at the University at Buffalo appears to be able to block the desire for cocaine and in the process reduce the likelihood of a number of behaviors associated with cocaine use, including addiction relapse.

If the results of testing on lab rats can be reproduced in humans, the compound may prove the first effective drug to treat cocaine addiction.

As they write in the journal Neuropsychopharmacology, Jun-Xu Li and his University at Buffalo colleagues have been employing a novel compound dubbed RO5263397. During the study the compound displayed the power to block a number of behaviors associated with cocaine addiction.

“This is the first systematic study to convincingly show that RO5263397 has the potential to treat cocaine addiction,” said Li, an assistant professor of pharmacology and toxicology in the UB School of Medicine and Biomedical Sciences.

RO5263397 is thought to moderate behavior associated with cocaine use by targeting a protein molecule called trace amine associated receptor 1, or TAAR 1.

When a person takes cocaine, the body produces the neurochemical dopamine. The dopamine in turn stimulates portions of the brain involved in producing feelings such as pleasure and euphoria, which in turn makes the person want to take more cocaine.

The Buffalo researchers decided to test the theory that using RO5263397 to stimulate TAAR 1 could curb cocaine abuse.

“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.

To test this theory, Li and his team gave RO5263397 to rats and observed its effect on conditioned place preference. Conditioned place preference, in this case, was the willingness of the rats to remain at or go back to a place where they had received cocaine injections. A strong conditioned place preference suggests the rats are chasing a cocaine high, which scientists call a rewarding effect.

“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 researchers found that RO5263397 made the rat version of cocaine abuse relapse less likely. “We found that RO5263397 markedly blocked the effect of cocaine or cocaine-related cues for priming relapse behavior,” Li said.

Li’s team is continuing to study RO5263397. The main areas of interest are how the compound reduces the risk of cocaine use relapse and how effective it is in doing so.

The research was funded by the National Institutes of Health.

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