Abstract
Impairments in opioid receptor signaling have been implicated in disordered eating. A functional variant of the OPRM1 gene is a guanine (G) substitution for adenine (A) at the 118 position of exon 1 (A118G). The influence of the A118G variant on binge eating behaviors and the effectiveness of pharmacotherapies used to treat binge eating have not been characterized. Mice were generated with A to G substitution at the 112 position on exon 1 to produce a murine equivalent of the human A118G variant. Homozygous female mice (AA or GG) were exposed to intermittent access to a highly palatable sweet-fat food with or without prior calorie deprivation to promote dietary-induced binge eating. There were no genotype-dependent differences in the dietary-induced binge eating. However, GG mice exposed to intermittent calorie restriction (Restrict) had higher body weights compared with GG mice exposed to intermittent sweet fat-food (Binge) and ad libitum feeding (Naive). Acute oral dosing of lisdexamfetamine (0.15, 0.5, and 1.5 mg/kg) or sibutramine (0.3, 1, and 3 mg/kg) did not produce genotype-dependent differences in binge-like eating. In addition, no genotype-dependent differences in binge-like eating were observed with chronic (14-day) dosing of lisdexamfetamine (1.5 mg/kg/day) or sibutramine (3 mg/kg/day). In the chronic dosing, body weights were higher in the GG Restrict compared with AA Restrict. Our findings suggest that the A112G polymorphism does not influence binge eating behaviors or pharmacotherapies for treating binge eating.
Highlights
Eating disorders, such as bulimia nervosa (BN), binge eating disorder (BED), and anorexia nervosa (AN), are psychiatric illnesses that are moderately influenced by genetic factors (Hinney and Volckmar, 2013; Juli and Juli, 2014)
Our mice were generated by similar methods used by others to generate a murine model of the A118G OPRM1 polymorphism (Mague et al, 2009)
Our findings in the present study indicate that female mice exposed to the Binge and Restrict Binge feeding schedules consumed excessive number of calories in a relatively short period of time and increased intake over the 6-week protocol, which was a result of the escalation in a highly palatable food intake from binge 1 to binge 12
Summary
Eating disorders, such as bulimia nervosa (BN), binge eating disorder (BED), and anorexia nervosa (AN), are psychiatric illnesses that are moderately influenced by genetic factors (Hinney and Volckmar, 2013; Juli and Juli, 2014). Several studies have suggested that the A118G OPRM1 variant has increased association with opioid use, alcohol dependence, and pain modulation (Bond et al, 1998; Tan et al, 2003; Kim et al, 2004; Bart et al, 2005; Pecina et al, 2015) This A118G OPRM1 polymorphism has been found at higher frequency in individuals diagnosed with BED in an obese population (n = 136) (Davis et al, 2009). The subjects with BED were more responsive to the hedonic properties of food (Davis et al, 2009) Despite these findings, the role of the A118G OPRM1 SNP in binge eating has not been further investigated. Understanding the interaction of the A118G polymorphism and lisdexamfetamine could potentially improve how this medication is prescribed and help identify potential responders and non-responders within BED populations
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