Drug addiction is a hugely complex condition that is caused by an intricate combination of physiological, psychological, and social factors, all of which makes it extremely difficult to treat. As such, neuroscientists tend to start by looking for ways to reverse the concrete biological changes that result from long-term drug abuse, and a study published this month in the Journal of Neuroscience suggests a major breakthrough could be on the horizon.

Like many drugs, cocaine leads to an increase in dopamine signaling in the brain’s reward circuit, creating an intense feeling of pleasure. However, repeated use can cause an imbalance in some of the brain regions involved in this circuit, such as the nucleus accumbens.

Previous research has shown that these changes occur because cocaine use causes an increase in levels of a protein called brain-derived neurotrophic factor (BDNF), which helps to control the growth, development, and connectivity of neurons. Because BDNF works by activating a type of brain receptor known as the TrkB receptor, scientists have in the past attempted to treat cocaine addiction by blocking these receptors.

Several studies have shown that inhibiting TrkB activation in the nucleus accumbens of cocaine-addicted rats does indeed alleviate their drug dependence, causing them to stop choosing cocaine-laced water over regular water.

However, there is a sting in the tail, as further research has shown that cocaine addiction has the exact opposite effect in another brain region called the prefrontal cortex, where it causes a decrease in TrkB activation. Only when scientists injected BDNF into this part of the brain did rats show a decrease in cocaine-seeking behavior.

^{Dopamine signaling in the reward circuit plays a major role in cocaine addiction. Blamb/Shutterstock}

Given the contradictory effects of BDNF on cocaine addiction in different brain regions, the authors of the latest study questioned what would happen if they blocked it across the entire brain. To investigate, they developed a TrkB antagonist that could cross the blood-brain barrier when injected into the bloodstream.

Results showed that inhibiting these receptors did indeed cause cocaine-addicted rats to significantly reduce their drug dependency behaviors, showing a reduced preference for cocaine over a sugar solution and less interest in self-administering the drug by pressing a lever.

When analyzing TrkB signaling in different brain areas, the study authors found that this was massively reduced in the nucleus accumbens, returning to normal levels seen in non-addicted rats, which they believe explains the “reversal” of the rats’ addiction. Interestingly, TrkB signaling also returned to normal in the prefrontal cortex, increasing despite the presence of an inhibitor.

In a statement, study co-author Candice Contet explained 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.”