Although alcohol abstinence is associated with improved health outcomes, addiction researchers have theorized that brain changes that occur during abstinence may increase a person’s risk of relapse.

To explore this theory, we studied how mice behaved after giving them long-term voluntary access to alcohol followed by a forced abstinence period. We found that a subset of the mice developed aversion-resistant alcohol intake – that is, they now drank alcohol despite the quinine we added to make it increasingly bitter. Moreover, compared to those who did not experience forced abstinence, these mice drank even larger quantities of the very bitter alcohol. These results suggest there are potential bodily challenges associated with abstinence that contribute to relapses in alcohol use disorder.

Next, we monitored the activity of a particular collection of cells in a portion of the brain known as the bed nucleus of the stria terminalis, or BNST. Researchers have previously found this small structure to be heavily implicated in alcohol use disorder symptoms such as anxiety and depression.

We found that allowing abstinent mice to reenter the setting where alcohol was previously available would lead them to attempt to drink even though the spout contained only water. These attempts were associated with activity in the BNST. Abstinent mice who had developed the taste for very bitter alcohol had more than double the activity in this brain area compared to mice that did not experience forced abstinence.