Ketogenic diet prevents sucrose withdrawal-induced anxiety-like behaviour in male mice

Abstract

Sugar bingeing has been shown to induce withdrawal effects when sugar is no longer available in the diet. In this study, we investigated the sex differences in sugar-addiction-like behaviour and the effects of the ketogenic diet on these outcomes. We used the two-bottle sucrose choice paradigm as a pre-clinical sucrose overeating and withdrawal model. Female mice consumed more sucrose than males when given free access to water and 10% sucrose for four weeks. One week of sucrose withdrawal after four weeks of consecutive sucrose overeating showed anxiety-like behaviour in male mice. However, the ketogenic diet did not affect sucrose overconsumption in males and females but prevented the sucrose withdrawal-induced anxiety-like behaviour in male mice with a concomitant increase in cFos mRNA in the prefrontal cortex. These findings provide evidence of sex differences in sucrose addiction-like behaviour and also indicate that a ketogenic diet may prevent sucrose withdrawal-induced anxiety-like behaviour in males. However, further research is needed to explore the underlying molecular mechanisms driving sex differences in sugar-addiction-like behaviour and the anxiolytic effects of the ketogenic diet.