Intracerebroventricular administration of MK-801 increases food intake through mechanisms independent of gastric emptying

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 287; no. 6; pp. R1462 - R1467
• Main Authors: Covasa, M, Hung, Chun-Yi, Ritter, R. C, Burns, G. A
• Format: Journal Article
• Language: English
• Published: United States 01.12.2004
• Subjects: Animals; Dizocilpine Maleate - administration & dosage; Dizocilpine Maleate - pharmacology; Energy Intake - drug effects; Feeding Behavior - drug effects; Feeding Behavior - physiology; Gastric Emptying - drug effects; Gastric Emptying - physiology; Injections, Intraventricular; Kinetics; Male; Rats; Rats, Sprague-Dawley; Sodium Chloride; Sucrose
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00471.2004

1 Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, Pennsylvania; and 2 Department of Veterinary Comparative Anatomy Pharmacology and Physiology, Program in Neuroscience, Washington State University, Pullman, Washington Submitted 13 July 2004 ; accepted in final form 7 September 2004 Systemic or hindbrain administration of MK-801, a noncompetitive N -methyl- D -aspartate receptor antagonist, increases meal size. To examine whether MK-801 enhances intake by increasing gastric emptying, we administered MK-801 (2.0 µg/3.0 µl) into the fourth ventricle [intracerebroventricular (ICV)] and measured feeding and gastric emptying of 5-ml NaCl or 15% sucrose loads. In a parallel experiment, we examined food intake and gastric emptying following intraperitoneal (IP) injection of MK-801 (100 µg/kg). MK-801, either IP or ICV, increased 30-min sucrose intake compared with control (12.3 ± 0.7 vs. 9.8 ± 0.5 and 16.6 ± 2.0 vs. 10.7 ± 0.7 ml, for IP and ICV administration, respectively). Also, IP MK-801 increased 5-min gastric emptying of NaCl (4.13 ± 0.1 ml emptied) and sucrose (3.11 ± 0.1 ml emptied) compared with control (3.75 ± 0.2 and 2.28 ± 0.1 ml emptied for NaCl and sucrose loads, respectively). In contrast, ICV MK-801 did not alter NaCl emptying (3.82 ± 0.1 ml emptied) compared with control (3.82 ± 0.3 ml emptied) and actually reduced gastric emptying of sucrose (2.1 ± 0.2 and 2.94 ± 0.1 ml emptied, for MK and vehicle, respectively). These data confirm previous results that systemic as well as hindbrain injection of MK-801 increases food intake. However, because ICV MK-801 failed to increase gastric emptying, these results indicate that MK-801 increases food intake through mechanisms independent of altered gastric emptying. dizolcipine; gastric distention; gastric tone; satiation Address for reprint requests and other correspondence: M. Covasa, Dept. of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State Univ., 126 South Henderson, Univ. Park, PA 16802 (E-mail: mzc13{at}psu.edu )