Housing Condition Differentially Impacts Escalation of Alcohol Intake, Relapse-Like Drinking, Anxiety-Like Behavior, and Stress History Effects by Sex

Abstract

Background: Stress triggers alcohol use and relapse to drinking, with different effects by sex. Women are more susceptible to stress-related alcohol misuse, and most stressors in rodents produce sexually divergent effects. Female rodents are particularly sensitive to the stress produced by solitary housing, yet the impact of housing conditions on the establishment, escalation, and post-abstinence potentiation of intermittent access alcohol drinking in male and female rats, and the interaction of these factors with stress history are not well described. Methods: Male (n = 62) and female (n = 64) Wistar rats were housed individually or in pairs separated by a perforated divider. Rats were exposed to light-cued footshock stress (stress history), or cues alone (control), once daily for 3 days, followed by 8 weeks' drinking under intermittent access to a 2-bottle choice (IA2BC), with 20% alcohol (v/v in water) available in addition to water for 24 hours on alternate days. After a 2-week forced abstinence, anxiety-like behavior was assessed via defensive withdrawal testing; then, IA2BC alcohol access was renewed for 2 weeks to model relapse-like behavior. Results: Pair-housed female rats did not increase their alcohol intake across the 8-week drinking period, unlike all other groups, and stress history did not significantly change alcohol consumption. After abstinence, anxiety-like behavior was greatest in pair-housed stress history males, whereas alcohol intake was significantly elevated only in female rats, particularly those in solitary housing. Conclusions: Together, these findings suggest that paired housing differentially contributes to behavior in male and female rats, blunting alcohol intake in females, and unmasking stress history effects on anxiety-like behavior in males.