Rat models of lactose intolerance: sexually dimorphic comorbidities with neuropsychiatric disorders modulated by tryptophan hydroxylase and the dopaminergic system

Some studies indicate a sexually dimorphic effect, along with a potential predisposition to neuropsychiatric disorders in patients with lactose intolerance. This study proposed rat models of lactose intolerance, evaluating the manifestation of behaviors related to neuropsychiatric disorders, their incidence in each sex, and the underlying neurobiological processes. Rats were exposed to two lactose-rich diets: a solution containing 14% lactose and a commercial milk formula. Clinical signs were monitored. Behavioral tests for anxiety (light-dark box), social preference, and depression (forced swim test) were conducted. Brain dopamine levels and genetic and epigenetic (DNA methylation) expressions of tryptophan hydroxylase (Tph)1 in the intestine were also examined. Both diets were well consumed and led to impaired stool consistency. Males exhibited anxiolytic-like behavior, increased striatal dopamine levels, and decreased cortical dopamine levels after consuming the lactose solution. In contrast, females showed anxiogenic-like behavior and decreased cortical dopamine levels following the commercial formula. Male socialization was impaired by both diets. Furthermore, both diets reduced Tph1 gene expression. In conclusion, this study introduced two rat models of lactose intolerance that revealed sexually dimorphic comorbidities with neuropsychiatric disorders, along with modulation of striatal and cortical dopaminergic systems and reduced genetic expression of the Tph1 enzyme in the intestine.