Involvement of the histaminergic system on maladaptive feeding behavior in ananimal model of binge eating in female rats

Binge eating disorder (BED) is the most common eating disorder, marked by recurrent episodes of excessive food intake within a short time frame, accompanied by a perceived loss of control over eating behavior. To date, lisdexamfetamine dimesylate remains the only FDA-approved pharmacotherapy for BED, highlighting the urgent need for novel therapeutic approaches. Emerging evidence points to a role for neuronal histamine in regulating stress responses and feeding behavior. In this study, we examined alterations in the histaminergic (HA) system at the gene expression level and evaluated the effects of a histamine-targeting compound in a well-characterized preclinical model of binge eating. Binge-like eating behavior was induced in female Sprague-Dawley rats through intermittent cycles of food restriction/refeeding combined with a frustration stress procedure and exposure to highly palatable food. Following repeated binge episodes, animals were sacrificed, and specific brain regions were collected for RT-PCR analysis of HA-related gene expression. Additionally, both acute and chronic treatments aimed at enhancing HA neurotransmission were tested in the same animal model. We observed significant changes in mRNA expression of HA receptors and histamine-metabolizing enzymes in various brain regions of binge eating rats compared to controls. Notably, pharmacological enhancement of HA transmission, both acutely and chronically, effectively suppressed binge-like behavior and prevented several of the associated molecular alterations. These findings suggest a potential involvement of the HA system in the pathophysiology of binge eating and support its consideration as a novel pharmacological target for BED treatment.