Caloric restriction modulates the monoaminergic and glutamatergic systems in the hippocampus, and attenuates age-dependent spatial memory decline

The beneficial effects of caloric restriction (CR) on health and life expectancy are well documented, although its ability to slow down age-dependent cognitive decline and the underlying biochemical changes remains unclear. Therefore, the aim of this study was to investigate the effects of CR on spatial memory in aged Wistar rats, as well as on monoaminergic and glutamatergic neurotransmission in the hippocampus (HPC). As such, animals maintained on different dietary regimes were trained in the Morris Water Maze (MWM): old rats (24–27 months) maintained on a 30% CR diet from four months of age, old rats (24–27 months) with unrestricted access to food (Ad Libitum); and adult rats (3–4 months) with Ad Libitum access to food. As well as their performance in the spatial memory task, monoamine levels, and NMDA and AMPA receptor subunit expression in the HPC were also assessed in these rats, as was the plasma corticosterone as a measure of the pituitary-adrenal response to stress. Accordingly, it appears that CR attenuates the spatial memory decline in aged rats and the age-associated decrease in the serotonin metabolite 5-HIAA, as well as the expression of the GluA1 and GluA2 AMPA receptor subunits in the HPC. In addition, CR augments the noradrenaline in this structure, although it did not modify the age-associated increase in plasma corticosterone levels. These findings support the positive effect of CR on spatial memory, suggesting that enhancing monoaminergic and glutamatergic neurotransmission in the HPC may help improve learning and memory in aged animals.