DELAY IN MEAL TERMINATION FOLLOWS BLOCKADE OF N-METHYL-D-ASPARTATE RECEPTORS IN THE DORSAL HINDBRAIN

We have reported that rats increased their intake of food, but not wat er, following an intraperitoneal injection of MK-801, a non-competitiv e antagonist of N-methyl-D-aspartate (NMDA)-activated ion channels. Th e antagonist appears to specifically interfere with signals that parti cipate in meal termination (satiety), thereby prolonging the meal and increasing its size. The anatomical site at which MK-801 acts to incre ase food intake is not known. However, vagal sensory neurons are known to participate in satiation for food. Furthermore, NMDA receptor immu noreactivity is present in the caudal nucleus of the solitary tract (N TS) where vagal sensory fibers terminate. Therefore, we hypothesized t hat MK-801 might increase food intake by blocking NMDA receptors in th e NTS. To test this hypothesis, we microinjected MK-801 directly into the hindbrain, immediately prior to a deprivation-induced meal of 15% sucrose. We found that sucrose intake was significantly increased foll owing injection of MK-801 (2 mu g/3 mu l) into the fourth ventricle. W hen MK-801 was injected directly into the caudomedial NTS, intake was increased significantly by doses as small as 198 ng/30 nl, while equiv alent injections into other hindbrain areas or the fourth ventricle di d not increase food intake. These data are consistent with control of food intake by endogenous glutamate and NMDA-type glutamate receptors located in the caudomedial NTS. (C) 1998 Elsevier Science B.V. All rig hts reserved.