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 water, following an intraperitoneal injection of MK-801, a non-competitive antagonist of N-methyl-d-aspartate (NMDA)-activated ion channels. The antagonist appears to specifically interfere with signals that participate in meal termination (satiety), thereby prolonging the meal and increasing its size. The anatomical site at which MK-801 acts to increase food intake is not known. However, vagal sensory neurons are known to participate in satiation for food. Furthermore, NMDA receptor immunoreactivity is present in the caudal nucleus of the solitary tract (NTS) where vagal sensory fibers terminate. Therefore, we hypothesized that MK-801 might increase food intake by blocking NMDA receptors in the 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 following injection of MK-801 (2 microgram/3 microliter) into the fourth ventricle. When MK-801 was injected directly into the caudomedial NTS, intake was increased significantly by doses as small as 198 ng/30 nl, while equivalent injections into other hindbrain areas or the fourth ventricle did 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.
Treece
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BR
College of Veterinary Medicine, Department of VCAPP, Room 205 Wegner Hall, Washington State University, Pullman, WA 99164-6520, USA.
Covasa
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M
Ritter
R C
RC
Burns
G A
GA
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012249:Rhombencephalon / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate