Cocaine addiction is a major problem in the United States, with deaths from the drug increasing by 42 percent between 2001-2014. Now, researchers may have found a way to reverse the issue.

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Researchers say their study suggests targeting TrkB receptors in the brain is a feasible treatment option for cocaine addiction.

A new study - led by researchers from The Scripps Research Institute (TSRI) in La Jolla, CA - describes how targeting and blocking the activity of a brain receptor called TrkB reduced cocaine-seeking behavior in mice, paving the way to a possible treatment for cocaine addiction.

Senior author Candice Contet, a biologist at TSRI, and colleagues recently published their findings in The Journal of Neuroscience.

Cocaine - also referred to as "coke," "crack," or "blow" - is an illicit drug that derives from the leaves of the Erythroxylum coca bush, native to the Andean region of South America.

Cocaine a powerful stimulant and very addictive. It activates the reward pathway in the brain - known as the mesocorticolimbic reward system - producing a sense of euphoria and pleasure, making users crave more of the drug.

According to the National Institute on Drug Abuse (NIDA), in 2014, around 913,000 people in the U.S. met the criteria for cocaine addiction, and of the almost 1.3 million emergency department visits for drug abuse in 2012, cocaine was involved in more than 500,000.

At present, there are no medications to treat cocaine addiction; behavioral interventions - such as contingency management, where people with cocaine use disorders are presented with motivational incentives to stop using the drug - are the primary form of treatment.

The new study from Contet and colleagues, however, suggests a pharmacological treatment for cocaine addiction may well be in the cards.

Targeting TrkB to combat cocaine addiction

Previous research in rat models of cocaine addiction has shown that repeated exposure to the drug leads to long-term changes in two major areas of the mesocorticolimbic reward system: the nucleus accumbens and the medial prefrontal cortex.

Scientists found such changes are partly triggered by modifications to the production of brain-derived neurotrophic factor (BDNF) - a protein that activates TrkB receptors - and injecting BDNF directly into the nucleus accumbens of rats increases cocaine-seeking behavior.

On the other hand, studies have found that inhibiting BDNF production or BDNF/TrkB signaling in the nucleus accumbens reduces signs of drug dependency in rats.

As such, researchers have looked to targeting and blocking TrkB as a way to combat addiction to cocaine and other drugs, but this has not been without its challenges.

For example, Contet and colleagues note that in the medial prefrontal cortex, BDNF reduces dependency behaviors - as demonstrated in rat studies. However, blocking BDNF/TrkB signaling in this region increases such behaviors.

"Based on these previous findings, we were very excited to investigate whether blocking TrkB receptors throughout the brain would be beneficial or detrimental in helping to reduce the motivation to take cocaine," says study co-author Michel M.M. Verheij, who was a research associate at TSRI when the study was conducted.

TrkB inhibitor reduced cocaine dependency in rats

For their study, the team tested the effects of a newly developed compound called cyclotraxin-B - which can travel from the bloodstream to the brain to block TrkB receptors - on rats that had learned to press a lever in order to self-administer cocaine.

This led the rats to use significantly less cocaine and press the lever fewer times. What is more, the treated rats were less likely to start using the drug again after a period of withdrawal. All of these factors represent a reduction in cocaine dependency.

What is more, the researchers found that cyclotraxin-B led to more normal TrkB signaling activity in the nucleus accumbens.

Interestingly, treatment with the the TrkB inhibitor also led to signs of more normal TrkB signaling activity in the medial prefrontal cortex.

"We suspect that the antagonist has its primary action in the nucleus accumbens, where it's logical that it would prevent the activation that is triggered by cocaine," explains Contet, "while what happens in the prefrontal cortex is probably a downstream consequence, rather than a direct effect of the TrkB antagonist in that region."

One important observation, the team notes, is that cyclotraxin-B did not lower the rodents' appetite for a tasty glucose solution. "That's good because it shows that the TrkB antagonist doesn't work by causing a general suppression of appetite or activity, but specifically reduces the sense of reward and motivation for cocaine," says Contet.

Overall, the team says these findings indicate that targeting and blocking TrkB receptors in the brain has the potential to curb cocaine abuse:

"Altogether, our data show that systemic administration of a brain-penetrant TrkB antagonist leads to brain region-specific effects and may be a potential pharmacological strategy for the treatment of cocaine addiction."

Read about how cocaine may cause brain cells to destroy themselves.