There is extensive research regarding the neural mechanisms involved in satiety and meal termination; in contrast, there is very limited understanding of how meal onset is regulated. On the basis of several converging lines of evidence, we hypothesized that hippocampal neurons form a memory of a meal and inhibit meal onset during the postprandial period. As a first step, we tested whether reversible inactivation of the hippocampus with muscimol infusions after the end of one meal would accelerate the onset of the next meal. To test this, adult male Sprague-Dawley rats (N = 23) were implanted with a cannula aimed at the right or left dorsal hippocampus and then trained to consume a 32% sucrose solution at a scheduled time daily. On the experimental day, hippocampal neuronal activity was temporarily disrupted during the postprandial period by infusing muscimol (0.5 μg/μl; 1 μl) 5 min after the rats stopped consuming the sucrose solution. Compared to vehicle infusions, muscimol infusions significantly decreased the latency to start the postinfusion meal and increased the size of the postinfusion meal. In addition, muscimol disrupted the relationship between the size of a meal and length of the following postprandial period. These effects of muscimol on meal onset were not due to an effect on the speed of consumption. Collectively, these findings are consistent with the hypothesis that hippocampal neurons suppress meal initiation during the postprandial period. Given that overeating can impair hippocampal function, these findings suggest that impaired hippocampal functioning is a cause and consequence of overeating and obesity.
