Neonatal serotonin reuptake inhibition reduces hypercaloric diet effects on fat mass and hypothalamic gene expression in adult rats

•Early SSRI-treated rats showed lower food intake and less NPY and 5-HT2C hypothalamic in adulthood•SSRI-treated rats showed increased 5-HT2C and decreased NPY expression after hypercaloric diet.•SSRI-treated rats had less fat pad mass after hypercaloric diet.

BackgroundSerotonin (5-HT) is involved in nervous system ontogenesis, and is important for neurotransmission and behavior modulation after the developmental stage. Alterations in 5-HT levels during the early period of life may signal to feeding behavior and hypothalamic genic expression changes in adulthood.ObjectivesInvestigate the effects of hypercaloric diet in adult rats submitted to neonatal serotonin reuptake inhibition on food intake, fat pad mass, plasmatic triglycerides/cholesterol and gene expression of hypothalamic peptides (POMC, NPY) and serotonin receptors (5-HT1B, 5-HT2C).MethodsIn each litter, 8 pups were divided into two groups: control (C) and fluoxetine (F). From the 1st to the 21st postnatal day, C pups received sterile saline while F pups received fluoxetine (10 mg/kg). From 180 to 215 days, a group of rats from C and F groups were fed hypercaloric diet (CH and FH, 421.4 Kcal/100 g) while the rest of animals from C and F groups fed chow diet (CC and FC).ResultsThe use of hypercaloric diet was associated with lower accumulation of white adipose tissue in adult rats subjected to neonatal serotonin reuptake inhibition. Adult rats of group FC showed decreased 5-HT2C and neuropeptide Y mRNA expression compared with control chow diet group (CC). After chronic use of a hypercaloric diet, the expression of 5-HT2C was higher in the FH group than the FC group and neuropeptide Y expression decreased in FH related to FC.ConclusionsThese findings suggest that neonatal serotonin reuptake inhibition is associated with better adaptation to hypercaloric diet in adult rats.