Shortening time for access to alcohol drives up front-loading behavior, bringing consumption in male rats to the level of females

Abstract

Background Incentives to promote drinking (“happy hour”) can encourage faster rates of alcohol consumption, especially in women. Sex differences in drinking dynamics may underlie differential health vulnerabilities relating to alcohol in women versus men. Herein, we used operant procedures to model the happy hour effect and gain insight into the alcohol drinking dynamics of male and female rats. Methods Adult male and female Wistar rats underwent operant training to promote voluntary drinking of 10% (w/v) alcohol (8 rats/sex). We tested how drinking patterns changed after manipulating the effort required for alcohol (fixed ratio, FR), as well as the length of time in which rats had access to alcohol (self-administration session length). Rats were tested twice within the 12 h of the dark cycle, first at 2 h (early phase of the dark cycle, “early sessions”) and then again at 10 h into the dark cycle (late phase of the dark cycle, “late sessions”) with an 8-h break between the two sessions in the home cage. Results Adult females consumed significantly more alcohol (g/kg) than males in the 30-min sessions with the FR1 schedule of reinforcement when tested late in the dark cycle. Front-loading of alcohol was the primary factor driving higher consumption in females. Changing the schedule of reinforcement from FR1 to FR3 reduced total consumption. Notably, this manipulation had minimal effect on front-loading behavior in females, whereas front-loading behavior was significantly reduced in males when more effort was required to access alcohol. Compressing drinking access to 15 min to model a happy hour drove up front-loading behavior, generating alcohol drinking patterns in males that were similar to patterns in females (faster drinking and higher intake). Conclusions This strategy could be useful for exploring sex differences in the neural mechanisms underlying alcohol drinking and related health vulnerabilities. Our findings also highlight the importance of the time of testing for detecting sex differences in drinking behavior.

Repeated footshock stress induces an escalation of cocaine self-administration in male and female rats: Role of the cannabinoid receptor 1

“…We demonstrate that within stress SA conditions, females alone show a unique “front-loading” behavior. This behavior has been previously shown in alcohol self-administration literature (Flores-Bonilla et al, 2021; Bauer et al, 2021), where females show greater consumption than males immediately after alcohol availability. The neurological basis for this behavior, and its sexually dimorphic regulation, remains unclear.…”

A critical review of front‐loading: A maladaptive drinking pattern driven by alcohol's rewarding effects

“…Female rodents typically outdrink males during alcohol self‐administration. This phenomenon has been reported across different species and self‐administration protocols (Li et al, 2019 ; Lourdes de la Torre et al, 2015 ; Oberlin et al, 2011 ; Priddy et al, 2017 ; Sneddon et al, 2020 ); and there is new evidence directly linking front‐loading in female rats as the reason for their higher total alcohol intake during operant self‐administration (Flores‐Bonilla et al, 2021 ). Further, it has been reported that female B6 mice with a binge drinking history front‐load more quinine‐adulterated alcohol than males (Bauer et al, 2021 ).…”

“…Therefore, front‐loading may contribute to the higher alcohol intake seen in alcohol vapor‐exposed animals, and it is possible that negative reinforcement could be a driving factor in the maintenance of front‐loading behavior. However, this does not rule out the possibility that front‐loading is driven by alcohol's rewarding effects and it should also be noted that alcohol front‐loading has been reported in rodents who do not self‐administer alcohol at levels which would induce dependence (Bauer et al, 2021 ; Flores‐Bonilla et al, 2021 ; Jeanblanc et al, 2019 ; Linsenbardt & Boehm, 2014 ). Another way of summarizing this is that although negative reinforcement as a driver of front‐loading cannot be ruled out, limited current data suggest that it is neither necessary nor sufficient for front‐loading to develop.…”

Greater resistance to footshock punishment in female C57BL/6J mice responding for ethanol

“…It is also important to consider that the observed results may be specific to the experimental parameters employed. For example, female rats have been shown to respond more than males for 10% EtOH when an FR1 schedule of reinforcement is used (Flores‐Bonilla et al, 2021). Interestingly, in agreement with our own work, this sex difference was not observed with an FR3 schedule of reinforcement.…”