Incubation of craving for alcohol: Is exercise a viable intervention

Incubation of craving refers to the time dependent increase in craving elicited by drug-associated cues. This is a well-documented phenomenon in clinical populations, and can be modelled in rodents by measuring drug-seeking in response to drug-associated cues. Although the mechanisms incubation of craving has been reasonably well-studied for drugs such as cocaine and methamphetamine, there is very little literature examining the effect for alcohol. This is despite the fact that incubation of craving is a robust effect in people seeking treatment for alcohol use disorder, and is an important contributor to high relapse rates.
We have robust evidence that rats trained to lever-press for alcohol show increased cue-elicited responses following a four-week period of abstinence compared to rats tested prior to abstinence. We have furthermore shown that this increase is reversed if the rats are permitted to use a running wheel during the abstinence period. Finally, we have shown that the changes in responding correlate with activity in the medial prefrontal cortex, one of the key regions in mediating relapse behaviour. In this project we will identify which pathways from the medial prefrontal cortex are recruited during incubation of changes, and show how plasticity in these pathways is changed across the course of abstinence. We will furthermore show how exercise is able to rescue these effects. Finally, we we look at whether a history of chronic alcohol intake changes activity in these pathways. Together these findings will not only explain the neural mechanism for incubation of craving, but will also provide evidence for exercise as an important adjunct for therapy in alcohol use disorder.