Inhibiting ventral hippocampal NMDA receptors and Arc increases energy intake in male rats

Abstract

Research into the neural mechanisms that underlie higher-order cognitive control of eating behavior suggests that ventral hippocampal (vHC) neurons, which are critical for emotional memory, also inhibit energy intake. We showed previously that optogenetically inhibiting vHC glutamatergic neurons during the early postprandial period, when the memory of the meal would be undergoing consolidation, caused rats to eat their next meal sooner and to eat more during that next meal when the neurons were no longer inhibited. The present research determined whether manipulations known to interfere with synaptic plasticity and memory when given pretraining would increase energy intake when given prior to ingestion. Specifically, we tested the effects of blocking vHC glutamatergic N-methyl-D-aspartate receptors (NMDARs) and activity-regulated cytoskeleton-associated protein (Arc) on sucrose ingestion. The results showed that male rats consumed a larger sucrose meal on days when they were given vHC infusions of the NMDAR antagonist APV or Arc antisense oligodeoxynucleotides than on days when they were given control infusions. The rats did not accommodate for that increase by delaying the onset of their next sucrose meal (i.e., decreased satiety ratio) or by eating less during the next meal. These data suggest that vHC NMDARs and Arc limit meal size and inhibit meal initiation.

Impact of the Aversive Effects of Drugs on Their Use and Abuse

“…Hippocampal damage has been shown to impair the ability of humans [ 301 – 303 ] and rats [ 304 , 305 ] to discriminate interoceptive satiety cues from hunger and to suppress food-reinforced conditioned response overconsumption. Rats with impaired hippocampal-dependent inhibitory control showed greater intake and meal frequency within a shorter interval [ 306 – 308 ] and greater weight gain within weeks [ 309 ] or months [ 310 ].…”