title: Cholinergic neurotransmission participates in increased food intake induced by NMDA receptor blockade.
abstract: MK-801, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, enhances gastric emptying while increasing food intake. Although our previously reported results implicate the vagus in MK-801's effect on feeding, it is not clear whether vagal motor fibers participate in the feeding response. Control of gastric emptying is exerted, in part, by cholinergic vagal motor neurons. Therefore, we examined the ability of MK-801 to increase meal size in the presence or absence of the muscarinic receptor antagonist atropine methyl nitrate. Both central and systemic administration of MK-801 significantly increased intake of 15% sucrose. Intraperitoneal injection of atropine abolished MK-801-induced increase in sucrose intake, whereas administration into the fourth ventricle had no effect. To determine whether augmentation of cholinergic tone produces an enhancement of food intake in the absence of MK-801, we tested the ability of cisapride, a gastric prokinetic agent that promotes acetylcholine release through an action on presynaptic serotonin (5-HT4) receptors, to increase sucrose consumption. Cisapride (500 microg/kg ip) induced a small but significant increase in 15% sucrose intake (15.5 +/- 0.5 ml) compared with NaCl (13.0 +/- 0.6 ml). Furthermore, when MK-801 (100 microg/kg ip) was given in combination with cisapride, intake was significantly higher (19.8 +/- 0.9 ml) than following either agent given alone. Pretreatment with atropine abolished the cisapride-induced increase in intake (12.1 +/- 0.9 ml) as well as the increased intake induced by combining MK-801 and cisapride. These results suggest that blockade of NMDA-gated ion channels in the hindbrain increases food intake, in part, via a peripheral muscarinic cholinergic mechanism.
authors.affiliation: Dept. of Nutritional Sciences, College of Health and Human Development, Pennsylvania State Univ., 126 S. Henderson, Univ. Park, PA, 16802-6504, USA. mzc13@psu.edu
authors.forename: Mihai
authors.initials: M
authors.lastname: Covasa
authors.forename: Robert C
authors.initials: RC
authors.lastname: Ritter
authors.forename: Gilbert A
authors.initials: GA
authors.lastname: Burns
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D020117:Cisapride / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D020546:Fourth Ventricle; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D011985:Receptors, Serotonin / Q000378:metabolism; D044422:Receptors, Serotonin, 5-HT4; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D010276:Parasympatholytics; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; D016291:Dizocilpine Maleate; D001285:Atropine; D000109:Acetylcholine; D020117:Cisapride