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.