NMDA receptor participation in control of food intake by the stomach

We previously reported that MK-801 (dizocilpine), an antagonist of N-methyl -D-aspartate (NMDA)-type glutamate receptors, increased meal size and durat ion in rats. MK-801 did not increase sham feeding or attenuate reduction of sham feeding by intraintestinal nutrient infusions. These results suggeste d that the MK-801-induced increase in meal size did not depend on antagonis m of postgastric satiety signals. Consequently, we hypothesized that the NM DA antagonist might increase food intake by directly antagonizing gastric m echanosensory signals or by accelerating gastric emptying, thereby reducing gastric mechanoreceptive feedback. To test this hypothesis, we recorded in take of 15% sucrose in rats implanted with pyloric cuffs that could be clos ed to prevent gastric emptying. Sucrose intake was increased when the pylor ic cuffs were open, allowing the stomach to empty. However, intake was not increased when the pyloric cuffs were inflated, causing gastric retention o f all ingested sucrose. Direct measurements of gastric emptying revealed th at MK-801 accelerated the emptying of 5-ml loads of 0.9% NaCl and 15% sucro se. Furthermore, MK-801 also accelerated the rate of emptying of freely ing ested sucrose regardless of the volume ingested. Taken together with our pr evious findings, these results indicate that blockade of NMDA receptors wit h MK-801 does not increase food intake by antagonizing gastric mechanosensa tion. Rather, it accelerates gastric emptying, and thereby may indirectly r educe gastric mechanoreceptive cues, resulting in prolongation of eating. M odulation of gastric emptying rate by NMDA receptors could play an importan t role in the control of meal sizes.