Intracerebroventricular administration of MK-801 increases food intake through mechanisms independent of gastric emptying.
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 microg/3.0 microl) 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 microg/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.
Covasa
M
M
Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, 126 South Henderson, University Park, PA 16802, USA. mzc13@psu.edu
Hung
Chun-Yi
CY
Ritter
R C
RC
Burns
G A
GA
D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D002149:Energy Intake / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride; D013395:Sucrose
D012965:Sodium Chloride; D013395:Sucrose; D016291:Dizocilpine Maleate