Gene Discovery Explains Why We Relapse and Could Lead to New Treatment

Understanding why recovering drug users relapse requires a host of complicated considerations. But a new study published today in Neuron reveals a previously unrecognized role for genetics, raising hopes of finding a medication to prevent relapse. 

Although drugs addiction, like any other behavior or environmental factor, cannot physically alter our DNA, they can alter the way that certain genes are expressed—a process known as epigenetic changes. Researchers from the Medical University of South Carolina wanted to know exactly what those changes were and how they happened. 

To better understand which genes are activated during early addiction and then later relapse, the team purposely addicted rats to cocaine, and then later deprived the rats of this drug. This allowed them to study what occurred in the brain both during the initial addiction stages, and then during relapse.

Results revealed a crucial role for an enzyme called histone deacetylase 5 (HDAC5). When this enzyme blocked a gene called NPAS4 from turning on, rats were less likely to seek drugs out during abstinence and “relapse.”

Related: To treat drug addiction, we'll still need jail time 

Although the enzyme and gene interaction had no effect on initial drug addiction, this subsequent connection may prove useful in treating individuals who are already addicted. A drug targeted to increase the gene-blocking enzyme could help recovering drug users stay off substances. Such drugs “could, in principle, help to reduce the urge to use drugs when a recovering addict encounters thing in the environment that they associate with drug use,” lead study investigator Dr. Christopher Cowan told Newsweek in an email.

“By understanding the epigenetic targets in the brain, we can identify new factors in the brain that ultimately mediate the strong associations between drug use and triggers in the addicts environment," Cowan explained.

09_27_cocaine This research could pave the way for an eventual more effective drug treatment. Spencer Platt/Getty Images

Before you get too overwhelmed by the science behind this research, take a deep breath. It’s really quite simple. Our genes are the blueprint of life, dictating many aspects our health from our appearance to our likeliness to develop certain diseases. However, having a gene isn’t enough. The gene must be expressed in order for it to have an effect on your health.

Related: One way to end the opioid epidemic. Let them die. 

Prior research had led the South Carolina team to investigate HDAC5. In earlier experiments, inhibiting HDAC5 did not prevent rats from forming addictions. This study is the first to show the enzyme's role in preventing later drug-seeking and relapses in rats put into periods of abstinence.

The team theorizes that targeting HDAC5 and its effect on NPAS4 may be key to preventing relapse in humans. The findings provide a starting place for future research into a treatment for humans, although such an intervention is still a long way off, Cowan notes.

Whether or not the results apply to humans is unknown. Although the brain chemistry of rats and humans may be different, addiction behavior is the same. In both rats and humans, certain environmental “cues” can trigger relapse. Former smokers are much more likely to light up at a night club than during Sunday mass, for example. 

The researchers are now looking at additional enzymes known to be affected by drug use and that control relapse. They hope that finding these proteins will lead to therapeutic drug targets for addiction treatments that would potentially make relapses a thing of the past. Cowan says this potential treatment would not be limited to substance abuse but could help other forms of mental illness because the brain mechanisms often overlap.

“By understanding how these connects are made, we can devise therapeutic strategies to reverse these strong triggers for relapse and increase the chances of sustained recovery from addiction,” says Cowan.

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