Evidence for different greater-persistence strategies under lower and higher challenge for alcohol in female rats

Problem alcohol drinking is a substantial social and economic burden. Studies show that the misuse of alcohol is increasing in women, and that women can face higher consequences from alcohol exposure, but females have historically been understudied. Thus, there is considerable interest in understanding potential sex-different and -similar cognitive/emotional strategies, and underlying mechanisms, for alcohol responding, which would inform more effective, personalized treatments. Here, we used large cohorts of adult Wistar rats (28 females, 30 males) to provide robust assessment of potential sex differences in responding for alcohol-only and under compulsion-like drinking with moderate or higher challenge (since intake despite negative consequences can be a major obstacle to human treatment). Females had similar total licking but higher intake for all drinking conditions. However, females had significantly longer bouts under alcohol-only and moderate challenge, but not higher challenge. Further, under higher challenge, females retained several aspects of responding not seen in males, including more efficient lick volume and earlier onset of longer bouts. In addition, females overall licked slightly faster, but licking speed averaged within-bout showed no sex differences, and female intake level under alcohol-only and moderate challenge was unlinked from licking speed (unlike males, where slower licking predicted lower intake). We interpret these differences as greater persistence-like responding but not vigor per se in females, and with different strategies under lower versus higher challenge. Finally, drinking levels did not differ across the estrous cycle, although ovariectomy reduced alcohol-only and moderate-challenge intake. Together, while many aspects were sex-similar, suggesting some common drinking mechanisms, there was clear evidence for (perhaps more nuanced) sex-different alcohol strategies, which might make an outsized contribution to excessive drinking since women can have more drinking problems. Thus, our studies provide important context for future work examining sex differences in pathological drinking mechanisms.