Different effects of stress on alcohol drinking behaviour in male and female mice selectively bred for high alcohol preference

Aims: The purpose of the present study was to examine the effects of stress on alcohol drinking behaviour in male and female mice with a genetic predisposition toward high alcohol preference (HAP2 line). Methods: Alcohol-naive male (n = 22) and female (n = 23) HAP2 mice were assigned to a restraint stress or no stress control group. Stress was initially applied for 2 h per day on 10 consecutive days. All mice were then given daily 2 h limited-access to a 10% v/v alcohol solution or water, with food freely available, for 21 days. Over the next 20 days, 2 h restraint stress was applied every other day immediately prior to 2 h access to alcohol and water. On intervening days, all mice received 2 h access to alcohol and water in the absence of stress. Following this phase of the study, the effects of restraint stress on acoustic startle reactivity was assessed in all mice. Finally, all mice were given continuous access to alcohol and water for 8 days. Results: Ten days of prior stress exposure did not significantly alter the acquisition of limited-access alcohol drinking. Subsequent exposures to intermittent restraint stress produced subtle but consistent effects on alcohol intake that differed in males vs females: stress increased alcohol intake in males and decreased alcohol intake in females. Restraint stress did not alter acoustic startle reactivity. Under continuous-access conditions after stress termination, the stress-induced increase in alcohol intake in males became more robust; however, in females, alcohol intake returned to the control group level. Conclusions: These findings suggest that the effects of stress on alcohol drinking in mice with a genetic predisposition toward high alcohol preference depend on sex.