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Background
One characteristic of alcohol use disorder is compulsive drinking or drinking despite negative consequences. When quinine is used to model such aversion‐resistant drinking, female rodents typically are more resistant to punishment than males. Using an operant response task where C57BL/6J responded for ethanol mixed with quinine, we previously demonstrated that female mice tolerate higher concentrations of quinine in ethanol than males. Here, we aimed to determine whether this female vulnerability to aversion‐resistant drinking behavior is similarly observed with footshock punishment.
Methods
Male and female C57BL/6J mice were trained to respond for 10% ethanol in an operant task on a fixed‐ratio three schedule. After consistent responding, mice were tested in a punishment session using either a 0.25 mA or 0.35 milliamp (mA) footshock. To assess footshock sensitivity, a subset of mice underwent a flinch, jump, and vocalize test in which behavioral responses to increasing amplitudes of footshock (0.05 to 0.95 mA) were assessed. In a separate cohort of mice, males and females were trained to respond for 2.5% sucrose and responses were punished using a 0.25 mA footshock.
Results
Males and females continued to respond for 10% ethanol when paired with a 0.25 mA footshock. Females alone continued to respond for ethanol when a 0.35 mA footshock was delivered. Both males and females reduced responding for 2.5% sucrose when punished with a 0.25 mA footshock. Footshock sensitivity in the flinch, jump, and vocalize test did not differ by sex.
Conclusions
Females continue to respond for 10% ethanol despite a 0.35 mA footshock, and this behavior is not due to differences in footshock sensitivity between males and females. These results show that female C57BL/6J mice are generally more resistant to punishment in an operant self‐administration paradigm. The findings add to the literature characterizing aversion‐resistant alcohol‐drinking behaviors in females.
Aversion‐resistant alcohol drinking paradigms that use quinine to punish self‐administration in rodents have uncovered sex differences, with females typically tolerating higher concentrations of quinine than males. Here we report that a similar sex difference is observed for footshock punishment. Males and females responded for alcohol when a 0.25 mA footshock was used but only females responded at 0.35 mA. These results suggest that female C57BL/6J mice are generally more resistant to punished alcohol responding in an operant self‐administration paradigm.