Cues that predict alcohol remain powerful long after prolonged sobriety, new research finds

Treating addiction to alcohol is no easy feat. While physical withdrawal symptoms can abate within days or weeks, research has shown that up to 90 per cent of alcoholics are expected to relapse within four years following treatment.

Nadia Chaudhri, an associate professor of psychology in the Faculty of Arts and Science, wants to figure out why. What are the triggers that can drive people with alcohol use disorder to relapse after months or years of successful sobriety?

In a recent paper published in the journal Alcoholism Clinical and Experimental Research, Chaudhri and her team described two new models they created to better understand relapse in alcohol-seeking rats. This project was spearheaded by Concordia graduate student Mandy LeCocq.

The researchers used auditory signals to create a Pavlovian cue-elicited craving for alcohol. For a period of about three weeks, the rats were trained using 10-second bursts of white noise followed by a drop of alcohol into a fluid port in their test cages.

“Over time, the rats come to learn that the white noise is a cue that predicts the delivery of alcohol,” says Chaudhri, a recipient of a Chercheur-boursier award from the Fonds de recherche du Québec – santé.

“As soon as the cue comes on, they enter the fluid port and wait for the alcohol to be presented to them. We can measure this conditioning over time and then we can see what factors influence that behaviour.”

What happens when you shut off the tap — and then turn it back on

With the rats now seeking alcohol in response to the cue, the researchers developed two separate models of relapse. Both involve first extinguishing that association between the cue and the delivery of alcohol. This phase is called “extinction,” and it occurs by presenting the cue repeatedly without any alcohol. “Over time, the rats stop responding to the cue,” Chaudhri explains.

The Spontaneous Recovery Paradigm is the first model. Three weeks after extinction has ended the researchers present the cue to the animals again.

“We found that the rats reacted very strongly,” she adds. “It’s as if they remembered that the cue was a signal for alcohol delivery.”

This result matters for humans because it suggests that reactions to cues that predict alcohol never really go away. You can stop reacting to cues, but then re-experiencing one at some point in the future might still be able to provoke a strong reaction that could lead to relapse.  

“Treatment can help to initially dampen reaction cues that predict alcohol,” Chaudhri says. “But then sometime after treatment is over, watching a vodka commercial on TV might once again trigger a craving for alcohol. These cue-induced cravings don’t seem to ever go away.”

In the second model, after researchers conduct extinction and rats are no longer responding to the cue, they are reintroduced to alcohol. The next day, their response to the cue by itself is tested. Rats once again react to the cue as though it is a signal for alcohol. This process, called reinstatement, leads to a complete return to responding to the trigger: after a taste of alcohol, the animal will immediately start reacting to cues for alcohol that they had previously ignored.

“That’s interesting to us because sometimes people who have become sober might think, ‘Well, I can use this drug once, or have just a sip of a drink,’” Chaudhri says. “We’re modelling the effect of what is not exactly a relapse, but certainly a lapse in drinking, on how a person reacts in the future to cues that predict alcohol.”

Chaudhri is hoping that her models help researchers understand the psychological and neural processes that drive relapse, and how alcoholics can avoid relapse in the future.

The Canadian Institutes of Health Research funded the study.

Read the cited paper: “Modeling Relapse to Pavlovian Alcohol‐Seeking in Rats Using Reinstatement and Spontaneous Recovery Paradigms.”