Research snapshot: New tools could help prevent relapse behavior in opioid addiction

Opioid addiction is a crippling problem in society, with an estimated 9 percent of Americans abusing opiates at some point in their life. In Minnesota, opiate overdose deaths have more than tripled since 2000.

Overcoming addiction is extremely challenging, and the risk of relapse persists. A new study from the University of Minnesota Medical School’s Department of Neuroscience identified a potential target for preventing morphine relapse in mice, which brings researchers closer to providing a way for recovering addicts to stay drug-free.

The study, published this month in the Proceedings of the National Academy of Sciences (PNAS), found that manipulating activity of a certain area of the brain could repress relapse behaviors in mice, thereby blocking continued morphine use.

“We’ve identified a specific cell group involved in relapse,” said senior author Mark Thomas, Ph.D., Associate Professor in the Departments of Neuroscience and Psychology. “In our model, we prevented the opioids— in this case, morphine specifically— from triggering relapse behavior.”

The research project by Matthew Hearing, Ph.D., a postdoctoral associate in the Thomas Lab, found that two different types of dopamine-receptive neurons, referred to as D1 and D2, could be driving addictive behavior. They’re located in a part of the brain called the nucleus accumbens, which plays a role in motivation and reinforcement.

It’s believed that D1 receptors encourage rewarding behavior, while D2 stops it. In mice with repeated morphine use, researchers found that D1 activity was persistently increased while D2 activity was reduced. It indicates that these dopamine-receptor cells may trigger relapse.

“Using manipulation to retune D1, we were able to stop morphine relapse,” Thomas said.

Retuning D1 was accomplished through a method called optogenetics. Optogeneticsis a fairly new technique in which brain cells are modified to become light-sensitive. Using light rays, a physician or researcher can non-invasively alter brain activity. This was the first time optogenetics has been used as an intervention for opioid relapse. While extremely promising, optogenetics has yet to be translated to humans.

Thomas’ group demonstrated that the antibiotic ceftriaxone also inhibits relapse. While consistent with previous studies, this is the first time researchers have identified ceftriaxone as preventing opiate relapse by inhibiting D1 neurons.

It’s especially crucial to study relapse, Thomas says, because time spent away from drugs reduces an addict’s drug tolerance, while the craving can remain intact. They can be drug-free for decades but the triggers will still be there.

“It’s pretty tough to prevent addiction, but maybe we can stop people from using drugs again,” Thomas said. “Our research identified a target, so let’s continue to research this and develop an intervention to prevent relapse for the millions of people suffering from addiction.”

Thomas’ team will continue to study opioid relapse. He hopes that they can also branch out in the future to apply their findings to other addictions like alcohol, nicotine or barbiturates.

This study was funded in part by the MnDRIVE initiative, which supports brain research and aims to improve the health and quality of life of Minnesotans. The National Institute on Drug Abuse also supported the study.

UMN Researchers Matthew Hearing, Jakub Jedynak, Stephanie Ebner, Anna Ingebretson, Anders Asp, Rachel Fischer, Clare Schmidt and Erin Larson all contributed to this study.

https://twin-cities.umn.edu/node/263711
University of Minnesota, Twin Cities
07/03/2018