Nucleus Accumbens Shell Orexin-1 Receptors Are Not Needed For Single-Bottle Limited Daily Access Alcohol Intake in C57BL/6 mice

Abstract

Excessive, binge drinking is a major contributor to the great harm and cost of alcohol use disorder. We recently showed, using both limited and intermittent-access two-bottle-choice models, that inhibiting nucleus accumbens shell (Shell) orexin-1-receptors (Ox1Rs) reduces alcohol intake in higher-drinking male C57BL/6 mice (Lei et al., 2019). Other studies implicate Ox1Rs, tested systemically, for several higher-drinking models, including the single-bottle, Rhodes Drinking-in-the-Dark paradigm. Here, we report studies examining whether Shell Ox1Rs contribute to alcohol intake in male mice using a single-bottle Limited Daily Access (LDA) drinking model modified from drinking-in-the-dark paradigms (2-h access starting 3 h into the dark cycle, 5 days per week). In addition, some previous work has suggested possible differences in circuitry for one- versus two-choice behaviors, and thus other mice first drank under a single-bottle schedule, and then an additional water bottle was included 2 days a week starting in week 3. Surprisingly, at the same time we were determining Ox1R importance for two-bottle-choice models, parallel studies found that inhibiting Shell Ox1Rs had no impact on drinking using the single-bottle LDA model, or when a second bottle containing water was added later during drinking. Furthermore, we have related Shell Ox1R regulation of intake to basal consumption, but no such pattern was observed with single-bottle LDA drinking. Thus, unlike our previous work showing the importance of Shell Ox1Rs for male alcohol drinking under several two-bottle-choice models, Shell Ox1Rs were not required under a single-bottle paradigm, even if a second water-containing bottle was later added. These results raise the speculations that different mechanisms could promote intake under single- versus two-bottle access conditions, and that the conditions under which an animal learns to drink can impact circuitry driving future intake.