Withdrawal from Extended, Intermittent Access to A Highly Palatable Diet Impairs Hippocampal Memory Function and Neurogenesis: Effects of Memantine

Background: Compulsive eating can be promoted by intermittent access to palatable food and is often accompanied by cognitive deficits and reduction in hippocampal plasticity. Here, we investigated the effects of intermittent access to palatable food on hippocampal function and neurogenesis. Methods: Male Wistar rats were either fed chow for 7 days/week (Chow/Chow group), or fed chow intermittently for 5 days/week followed by a palatable diet for 2 days/week (Chow/Palatable group). Hippocampal function and neurogenesis were assessed either during withdrawal or following renewed access to palatable food. Furthermore, the ability of the uncompetitive N-methyl-d-aspartate receptor (NMDAR) antagonist memantine to prevent the diet-induced memory deficits and block the maladaptive feeding was tested. Results: Palatable food withdrawn Chow/Palatable rats showed both a weakened ability for contextual spatial processing and a bias in their preference for a “novel cue” over a “novel place,” compared to controls. They also showed reduced expression of immature neurons in the dentate gyrus of the hippocampus as well as a withdrawal-dependent decrease of proliferating cells. Memantine treatment was able both to reverse the memory deficits and to reduce the excessive intake of palatable diet and the withdrawal-induced hypophagia in food cycling rats. Conclusions: In summary, our results provide evidence that withdrawal from highly palatable food produces NMDAR-dependent deficits in hippocampal function and a reduction in hippocampal neurogenesis.