Altered reward processing following sucrose bingeing in male and female mice.

Objectives: Binge eating disorder (BED) is the most prevalent eating disorder associated with multiple adverse health effects, especially mental health issues, including substance use disorders and mood and anxiety disorders. Given these high comorbidities, the objective of our study was to examine whether bingeing behavior would lead to altered perception of reinforcing properties of EtOH and changes in well-being. Methods: We used a sucrose bingeing model based on an intermittent access paradigm with a two-bottle choice, without fasting, in male and female mice. We examined the effect of 2-week sucrose paradigm on ethanol-reinforcing properties using a conditioned place preference test (CPP). Well-being, anxiety- and depressive-like behavioral tests were performed to assess emotional state following 2 and 8-week sucrose bingeing paradigm. Results: Mice with intermittent access to sucrose developed a binge-like behavior assessed by higher sucrose intake and escalation rate during the 1st hour of access, in comparison with mice with a continuous sucrose access. We show for the first time that sucrose bingeing in mice modifies positive reinforcing effect of EtOH in a CPP paradigm without marked alteration of emotional state. Interestingly, prolonging sucrose access for 8 weeks revealed an exacerbated bingeing behavior in female mice, and some signs of emotional state alterations in female with continuous access. Discussion: In sum, our findings broaden the understanding of behavioral alterations associated with bingeing, highlighting the need to investigate addictive-like properties of palatable food both in male and female mice.

Binge sucrose-induced neuroadaptations: A focus on the endocannabinoid system.

Binge eating, the defining feature of binge eating disorder (BED), is associated with a number of adverse health outcomes as well as a reduced quality of life. Animals, like humans, selectively binge on highly palatable food suggesting that the behaviour is driven by hedonic, rather than metabolic, signals. Given the links to both reward processing and food intake, this study examined the contribution of the endocannabinoid system (ECS) to binge-like eating in rats. Separate groups were given intermittent (12 h) or continuous (24 h) access to 10% sucrose and food over 28 days, with only the 12 h access group displaying excessive sucrose intake within a discrete period of time (i.e., binge eating). Importantly, this group also exhibited alterations in ECS transcripts and endocannabinoid levels in brain reward regions, including an increase in cannabinoid receptor 1 (CB1R) mRNA in the nucleus accumbens as well as changes in endocannabinoid levels in the prefrontal cortex and hippocampus. We then tested whether different doses (1 and 3 mg/kg) of a CB1R antagonist, Rimonabant, modify binge-like intake or the development of a conditioned place preference (CPP) to sucrose. CB1R blockade reduced binge-like intake of sucrose and blocked a sucrose CPP, but only in rats that had undergone 28 days of sucrose consumption. These findings indicate that sucrose bingeing alters the ECS in reward-related areas, modifications that exacerbate the effect of CB1R blockade on sucrose reward. Overall, our results broaden the understanding of neural alterations associated with bingeing eating and demonstrate an important role for CB1R mechanisms in reward processing. In addition, these findings have implications for understanding substance abuse, which is also characterized by excessive and maladaptive intake, pointing towards addictive-like properties of palatable food.

Deletion of mu opioid receptors reduces palatable solution intake in a mouse model of binge eating.

Binge eating in humans is driven by hedonic properties of food, suggesting that brain reward systems may contribute to this behaviour. We examined the role of mu opioid receptors (MOP) in binge eating by examining sweet solution intake in mice with genetic deletion of the MOP. Wildtype and MOP knockout mice had 4 hours access to food in the home cage combined with limited (4 hours) access to sucrose (17.1% w/v) or saccharin (0.09% w/v), or continuous (24 hours) access to sucrose. Only limited access groups exhibited binge intake, measured as increased solution consumption during the first hour. Knockout mice consumed less solution and food during the first hour as well as less food each day compared with wildtype mice. Limited access groups consumed more food and gained more weight than continuous access groups, and the effect was magnified in saccharin-consuming mice. Indeed, the increased food consumption in animals given limited access to saccharin was so excessive that caloric intake of this group was significantly higher than either of the sucrose groups (limited or continuous access). Within this group, females consumed more food per bodyweight than males, highlighting important sex differences in feeding behaviours under restricted access schedules.