UC Santa Barbara

In alcohol-dependent humans, cessation of alcohol consumption produces a dysphoric, anxiogenic state that can persist into protracted withdrawal. This aversive withdrawal-induced affective state is theorized to contribute to the negative reinforcing properties of alcohol that maintains and/or precipitates relapse in those suffering with alcoholism. Despite this and evidence that alcohol withdrawal increases biochemical indices of stress, there are relatively few published studies examining the impact of cessation from binge drinking on behavioral measures of negative affect. To this end, 60 C57BL/6 mice were allowed to consume alcohol under modified Drinking-in-the-Dark (DID) procedures, which consisted of access to a sipper tube containing either 20% alcohol or water for 2hrs/day, 5 days/week, for 6 consecutive weeks. Half of the mice from each drinking group were subjected to a 2-day behavioral test battery consisting of conventional assays of anxiety and depression either 24hrs (n=30) or 21 days (n=30) into withdrawal. A combined analysis revealed higher indices of anxiety assessed in the light/dark shuttle box, novel object encounter, elevated plus maze, and marble burying tests in alcohol-drinking (AD) compared to water-drinking (WD) controls, independent of withdrawal duration. AD mice also showed a shorter latency to float on the first day of the forced swim test, indicating a higher prevalence of behavioral despair; however, these mice also showed an increase in swimming behavior on a re-exposure session, suggesting impaired emotional memory. The present results indicate that increases in anxiety and depression emerge very early after cessation of drinking and persist into protracted withdrawal, suggesting that a history of heavy binge drinking produces enduring neuroadaptations within brain circuits mediating emotional arousal.