Overcoming memories that trigger cocaine relapse

October 17, 2012

Researchers from the University of Wisconsin-Milwaukee (UWM) have identified mechanisms in the brain responsible for regulating cocaine-seeking behavior, providing an avenue for drug development that could greatly reduce the high relapse rate in cocaine addiction.

The research reveals that stimulation of certain promotes inhibition of cocaine-associated memories, helping addicts to stop drug use. This is achieved through enhancing a process called " learning," in which cocaine-associated memories are replaced with associations that have no drug "reward." This reduces drug-seeking behavior in rats.

The work was presented today at the annual meeting of the Society for Neuroscience in New Orleans by Devin Mueller, UWM assistant professor of psychology, and doctoral student James Otis.

There are currently no FDA-approved medications to treat , only treatments that address , says Mueller. Abuse is maintained, in part, through exposure to environmental cues that trigger cocaine-related memories which lead to craving and relapse in recovering addicts. Currently, is used to help recovering addicts suppress their drug-seeking behavior, but with limited success. In exposure therapy, a patient is repeatedly exposed to stimuli that provoke craving. With repeated exposure, the patient experiences extinction, leading to reduced craving when presented with those .

If extinction could be strengthened, it would increase the effectiveness of exposure therapies in preventing relapse.

Isolating the receptor

The team found that a specific variant of the , those which contain the NR2B subunit, are critical for extinction learning. They also discovered that drugs known to enhance NR2B function strengthened extinction because they act specifically in a region of the brain that regulates learned behaviors. In their investigation, researchers conditioned rats to associate one distinct chamber, but not another, with cocaine. Following conditioning, the rats were tested for a place preference by allowing drug-free access to both chambers. Rats demonstrating cocaine-seeking behavior spent significantly more time in the previously cocaine-associated chamber. Over several cocaine-free test sessions, addicted rats lost their place preference through extinction learning.

To examine the neural mechanisms of extinction, the researchers administered ifenprodil, which blocks NR2B-containing NMDA receptors, immediately after an extinction test. Ifenprodil-treated rats continued to spend more time in the cocaine-associated chamber even in the absence of cocaine, while saline-treated rats did not. These results were also replicated through specific infusion of ifenprodil into the brain's infralimbic cortex, localizing a key brain structure in arresting cocaine-seeking.

Other avenues

The results indicate that enhancing NR2B function would boost the effectiveness of extinction-based exposure therapies. Although there are currently no NR2B-enhancing drugs, the NR2B containing receptor can be stimulated using other molecular pathways, says Mueller.

An example is the brain derived neurotrophic factor (BDNF) signaling cascade, which is implicated in neuron survival and growth. The authors targeted this cascade by directly administering BDNF into the infralimbic cortex. In extinction tests, administration of BDNF caused rats to lose their preference for the cocaine-associated chamber faster than rats given a placebo.

Mueller and Otis took these findings even further toward possible therapeutic intervention for addicts.

One issue with giving BDNF to humans is that it is unable to reach the brain through the bloodstream. Therefore, researchers next targeted the TrkB receptor, which is where BDNF normally binds. They did so with a newly synthesized drug that is able to reach the brain due to its small molecular size. This TrkB receptor agonist, known as 7,8 dihydroxyflavone, also strengthened extinction when given to during extinction training. The authors conclude that combining TrKB receptor stimulation simultaneously with exposure therapy could be an effective treatment for cocaine abuse, reducing craving and the potential for relapse.

Related Stories

Treating addiction by eliminating drug-associated memories

April 23, 2009

Addicts, even those who have been abstinent for long periods of time, are often still vulnerable to their own memories of prior drug use.  For example, exposure to the same environment in which they commonly used drugs - ...

Recommended for you

Research grasps how the brain plans gripping motion

July 28, 2015

With the results of a new study, neuroscientists have a firmer grasp on the way the brain formulates commands for the hand to grip an object. The advance could lead to improvements in future brain-computer interfaces that ...

New research rethinks how we grab and hold onto objects

July 28, 2015

It's been a long day. You open your fridge and grab a nice, cold beer. A pretty simple task, right? Wrong. While you're debating between an IPA and a lager, your nervous system is calculating a complex problem: how hard to ...

It don't mean a thing if the brain ain't got that swing

July 27, 2015

Like Duke Ellington's 1931 jazz standard, the human brain improvises while its rhythm section keeps up a steady beat. But when it comes to taking on intellectually challenging tasks, groups of neurons tune in to one another ...

Static synapses on a moving structure: Mind the gap!

July 22, 2015

In biology, stability is important. From body temperature to blood pressure and sugar levels, our body ensures that these remain within reasonable limits and do not reach potentially damaging extremes. Neurons in the brain ...

Sleep makes our memories more accessible, study shows

July 27, 2015

Sleeping not only protects memories from being forgotten, it also makes them easier to access, according to new research from the University of Exeter and the Basque Centre for Cognition, Brain and Language. The findings ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.