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bioRxiv · 10.1101/2021.06.01.446588

SHORTENING TIME FOR ALCOHOL ACCESS DRIVES UP FRONT-LOADING BEHAVIOR, BRINGING CONSUMPTION IN MALE RATS TO THE LEVEL OF FEMALES

Flores-Bonilla, A.·De Oliveira, B.·Silva-Gotay, A.·Lucier, K. W.·Richardson, H. N.
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Abstract

Alcohol can have more detrimental effects on mental health in women, even when intake is comparable or higher in men. This may relate to a differential pattern of drinking, e.g., how rapidly alcohol is consumed. We used operant procedures to gain insight into sex differences in the drinking dynamics of rats. 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 animals had access to alcohol (self-administration session length). Rats were tested twice within the 12 hours of the dark cycle, at 2 hours (early sessions) and 10 hours into the dark cycle (late sessions). As expected, adult females consumed significantly more alcohol than males in the 30-minute sessions with the FR1 paradigm. Alcohol consumption within females was higher in the late sessions compared to early sessions, whereas this difference was not found within males. "Front-loading" of alcohol (heavier drinking in the first five minutes of the session) was the primary factor underlying higher consumption in females, and this sex difference was accentuated in the late sessions. Increasing the effort required from FR1 to FR3 reduced alcohol drinking in both sexes. Front-loading behavior remained in females in both early and late sessions, whereas males exhibited minimal front-loading behavior only in the early sessions. Compressing drinking access to 15-minutes drove up front-loading behavior, producing total alcohol intake levels that were comparable in both sexes. This strategy could be useful for exploring sex differences in the effect of voluntary alcohol drinking on the brain. Our findings also highlight the importance of the time of testing for detecting sex differences in drinking behavior. HighlightsO_LIVoluntary alcohol drinking is higher in adult female rats compared to adult male rats. This sex difference is most pronounced in the later phase of the dark cycle, and when the operant effort is minimal (when 1 lever press gives 1 reward: fixed ratio 1, FR1). C_LIO_LIHigher alcohol intake in females is primarily due to "front-loading," or the rapid consumption of alcohol within the first 5 minutes of access. C_LIO_LIIncreasing the effort required to obtain alcohol from FR1 to FR3 dampens "front-loading" drinking behavior, resulting in similar levels of total intake in males and females. C_LIO_LICompressing the time of access to 15 minutes drives up "front-loading" to such a degree that animals end up consuming more alcohol in total than they do in 30-minute sessions. In males, this increase in drinking is large enough that it eliminates the sex difference in total alcohol intake. C_LI Visual Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/446588v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@8a1846org.highwire.dtl.DTLVardef@3fce34org.highwire.dtl.DTLVardef@fae52forg.highwire.dtl.DTLVardef@1dc940a_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Flores-Bonilla, A., De Oliveira, B., Silva-Gotay, A., Lucier, K. W., Richardson, H. N.. 2021-06-03. SHORTENING TIME FOR ALCOHOL ACCESS DRIVES UP FRONT-LOADING BEHAVIOR, BRINGING CONSUMPTION IN MALE RATS TO THE LEVEL OF FEMALES. https://doi.org/10.1101/2021.06.01.446588

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