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Diet-induced obesity is associated with premature cognitive decline. Elevated consumption of fats and sugars in humans and rodents has been associated with deficits in recognition memory, which is modulated by the hippocampus. Alterations in excitatory and inhibitory neurotransmitters in this area have been observed after hypercaloric diets, but the effects on episodic-like memory are not conclusive. To investigate the effects of hypercaloric diets on memory and their relationship with γ-aminobutyric acid (GABA), glutamate and glutamine and their genetic expression in the hippocampus. A control diet (CD), a high-fat diet (HFD) and a combined high-fat–high-fructose diet (HFFrD) were administered to 30 C57BL/6 adult mice for 10 weeks. The discrimination indexes and exploration time of the novel object recognition (NOR) and novel object location (NOL) tasks were evaluated and GABA, glutamate and glutamine concentrations and their genetic expression were obtained from the hippocampus. The HFFrD induced lower discrimination indexes, decreased exploration time in the recognition memory tasks, and lowered the concentrations of glutamate and glutamine, and HFD increased their expression in the hippocampus. These findings suggest that a possible adaptative long-term mechanism in the hippocampal neurotransmitters, and this possibility may underlie the episodic-like memory deficits in mice fed HFD and HFFrD.

High-fat and combined high-fat–high-fructose diets impair episodic-like memory and decrease glutamate and glutamine in the hippocampus of adult mice