Brain serotonin deficiency and fluoxetine lead to sex-specific effects on binge-like food consumption in mice.

Rationale: Although pharmacotherapies are often effective in reducing binge eating in conditions such as bulimia nervosa and binge eating disorder, subsets of patients do not benefit sufficiently from existing treatments, and the reasons for treatment failure remain unclear.

Objectives: This study aimed to evaluate whether genetic reductions in brain serotonin influence binge eating and/or the ability of fluoxetine, a selective serotonin reuptake inhibitor, to reduce binge eating in mice.

Methods: This study used a validated model of binge-like consumption of high-fat diet to compare binge-like food intake in control and fluoxetine-treated wild-type and serotonin-deficient mice from the tryptophan hydroxylase 2 (R439H) knock-in line.

Brain 5-HT Deficiency Prevents Antidepressant-Like Effects of High-Fat-Diet and Blocks High-Fat-Diet-Induced GSK3β Phosphorylation in the Hippocampus.

Obesity is associated with an increased risk of depression and anxiety disorders, but the nature of the relationship(s) between obesity and mental illness remains highly controversial. Some argue that depression and anxiety lead to increased consumption of "comfort foods," the intake of which reduces negative affect and promotes obesity. In contrast, others have theorized that negative affect results from chronic excessive consumption of highly palatable foods.