Differential Effects of Dietary MSG on Hippocampal Dependent Memory Are Mediated by Diet

Introduction: Free glutamate is a common dietary flavor enhancer and is also an important excitatory neurotransmitter in the body. A good number of food additives which contain glutamate are found in the Western Diet, and this diet has also been linked to increased risk of cognitive dysfunction. Objective: To examine the effects of dietary glutamate on hippocampal and non-hippocampal memory performance, and whether consuming a diet high in fat/sugar could influence any observed associations. Methods: Sixty-four adult male Sprague-Dawley rats were trained concurrently on two different discrimination problems: (1) Pavlovian serial feature negative (sFN) discrimination, in which a brief tone stimulus was reinforced with sucrose pellets when it was presented alone (T+ trials) and non-reinforced on trials when it was preceded by the presentation of a brief light (LT- trials); and (2) a simple discrimination (SD) problem in which a white noise (WN+) cue was reinforced with sucrose pellets and a clicker (C-) stimulus was not reinforced. Previous research has shown that sFN, but not SD performance, depends on the functional integrity of the hippocampus. After solving both problems, the rats were assigned to one of four ad libitum-fed diet groups, matched on weight and discrimination performance: (1) high fat, high sugar western-style diet (WD), (2) standard laboratory rodent chow diet (chow), (3) WD + monosodium glutamate (MSG), or (4) chow + MSG. Results: After 14 weeks, rats fed WD had higher adiposity than rats fed chow. Consistent with previous findings, rats fed WD exhibited impaired performance on the sFN problem, but not on the SD, relative to rats fed chow. Adding MSG to WD abolished this impairment, whereas rats fed chow + MSG had impaired sFN performance compared to rats fed chow alone. No differences in performance on the SD task were observed. Conclusion: This study demonstrates differing effects of dietary glutamate on hippocampal dependent memory function, with MSG impairing hippocampal function in animals receiving chow, while improving hippocampal function in animals receiving a Western-type diet, high in fat and sugar. More research will be needed to explore the cause of these differential effects.