Cocaine addiction relapse reversed in rats

Washington, August 6

Scientists have found that a naturally occurring protein linked to addictive behaviours can prevent cocaine relapse in rats, a finding that may pave the way for treating patients of drug abuse.

When a common protein brain-derived neurotropic factor (BDNF) was applied to the nucleus accumbens - a tiny cluster of nerve cells deep in the brain - immediately before cocaine-seeking behaviour, cocaine relapse was significantly reduced in a preclinical model, according to researchers from Medical University of South Carolina (MUSC) in the US.

“We discovered that a very common protein in the brain has an additional significant role in addiction relapse,” said Ana-Clara Bobadilla, a postdoctoral scholar at MUSC.

The nucleus accumbens plays a critical role in reward-seeking behaviours. It combines signals from other parts of the brain to drive reward-motivated behaviours.

Researchers showed for the first time that BDNF has both a time- and location-dependent beneficial role when administered before a cue-induced relapse event.

In the preclinical model of cocaine addiction, rats are allowed to self-administer cocaine while hearing an auditory cue. The rats learn to associate the cue with the reward of cocaine and continue to self-administer when hearing the cue.

In the extinction phase, the rats are not allowed access to cocaine or the cue associated with the drug. In the last phase, called reinstatement, the rats seek out cocaine upon hearing the cue previously associated with cocaine administration.

The drug-seeking behaviour that the rats display is similar to how drug cues induce craving in humans and thus are more likely to relapse.

Examples of such cues in humans are visiting a neighbourhood in which drugs were previously bought or seeing a friend with whom they took drugs.

The protein BDNF plays essential roles in neuron development and memory in multiple brain regions. While other research groups have studied how BDNF administration affects drug self-administration and relapse, no one has looked at what happens if BDNF is given immediately before relapse.

“An important aspect of this study is that while others have shown that BDNF is important for establishing the state of addiction, we find that can also be used to reverse addiction,” said Peter Kalivas, a professor at MUSC.

“This exemplifies that the primary effect of BDNF is to promote changes in the brain, and that this capacity to change the brain contributes to how people get addicted, but also can be harnessed to remove brain pathologies such as drug addiction,” Kalivas said.

The findings are the first to show that applying BDNF to the nucleus accumbens immediately before the reinstatement phase, when the rats are once again seeking cocaine due to cue exposure, greatly reduces relapse.

The discovery opens the doors for further investigation with BDNF and the nucleus accumbens in particular, as it is currently not known how BDNF suppresses cocaine addiction relapse. PTI