Brain serotonin in high-fat diet-induced weight gain, anxiety and spatial memory in rats

Objectives: Effects of high-fat diet (HFD) consumption on body weight gain and its consequences on anxiety, learning and memory, and serotonin metabolism (5-hydroxytryptamine; 5-HT) in the hypothalamus and hippocampus are determined in rats. Methods: Male Wister rats treated with HFD or normal diet (ND) for 12 weeks to monitor food intakes, body weight changes, activity in an open field, anxiety in an elevated plus maze and learning/memory in Morris water maze. Animals decapitated to collect serum for determining leptin by an ELISA kit. The hippocampus and hypothalamus dissected out for determining 5-HT, its metabolite 5-hydroxyindoleacetic acid (5-HIAA) and its precursor tryptophan by HPLC-EC. Results: Despite a significant decrease in the cumulative weekly food intake, gain in body weight was greater in HFD than ND treated rats. Total caloric intakes were not different in the two groups. The consumption of HFD resulted in an enhancement of exploratory activity and reduction in anxiety. It improved learning acquisition and memory retention but impaired reference memory. There was an attenuation of 5-HT in the hypothalamus, and an enhancement of 5-HT and 5-HIAA in the hippocampus, but no effect occurred on tryptophan levels in the hypothalamus or the hippocampus. Serum leptin levels increased in HFD treated animals. Conclusion: Serotonin acting via the hypothalamus and hippocampus is involved in HFD-induced weight gain, anxiety reduction and modulation of cognitive performance.