Brain Serotonin Deficiency and Fluoxetine Lead to Sex-Specific Effects on Binge Eating in Mice.

Binge eating disorder (BED), the most common eating disorder in the USA, negatively impacts psychological and physical health. Although the neurobiological basis of BED remains unknown, serotonergic dysfunction has been hypothesized to contribute to this condition. This study tested the hypothesis that brain serotonin deficiency will increase binge eating and block reductions in binge eating induced by fluoxetine. Binge eating was measured in wild-type and serotonin-deficient mice after acute and chronic fluoxetine administration. RNA was isolated from the raphe, and real-time PCR was performed to evaluate gene expression. Males with low serotonin binge ate more than wild-type mice at baseline, and fluoxetine reduced binge eating in both genotypes. Gene expression analyses revealed no significant genotype or drug effects on p11 expression in males, but fluoxetine significantly reduced the expression of 5HT1A receptor but not 5HT2A. In females, fluoxetine reduced binge eating in wild-type but not serotonin-deficient mice, and no baseline difference in binge eating was observed. Real-time PCR revealed no significant main effects of genotype or drug on p11, 5HT1A, or 5HT2A expression. However, a significant genotype by drug interaction was observed for p11 expression in which fluoxetine reduced p11 expression in wild-type mice and increased it in serotonin-deficient animals. These results highlight the importance of sex as a modifying factor in the relationship between binge eating and serotonin levels and suggest that serotonin deficiency can modify sensitivity to fluoxetine-induced reductions in binge eating, perhaps by impacting transcriptional responses to fluoxetine.