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Am J Physiol Regul Integr Comp Physiol (September 9, 2004). doi:10.1152/ajpregu.00471.2004
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Submitted on July 13, 2004
Accepted on September 7, 2004

INTRACEREBROVENTRICULAR ADMINISTRATION OF MK-801 INCREASES FOOD INTAKE THROUGH MECHANISMS INDEPENDENT OF GASTRIC EMPTYING

Mihai Covasa1*, Chun-Yi Hung1, Robert C Ritter2, and Gilbert A Burns2

1 Nutritional Sciences, The Pennsylvania State University, College of Health and Human Development, University Park, PA, USA
2 Veterinary Comparative Anatomy Pharmacology and Physiology, Washington State University, Program in Neuroscience, Pullman, WA, USA

* To whom correspondence should be addressed. E-mail: mzc13{at}psu.edu.

Systemic or hindbrain administration of MK-801, a non-competitive NMDA receptor antagonist increases meal size. To examine whether MK-801 enhances intake by increasing gastric emptying, we administered MK-801 (2.0µg/3.0µl) into the fourth ventricle (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 injection (IP) of MK-801 (100 µg/kg). MK-801, either IP or ICV increased 30-min sucrose intake compared to control (12.3±0.7 vs 9.8±0.5 and 16.6±2.0 vs 10.7±0.7ml, for IP and ICV administration, respectively). Also, IP MK-801 increased 5-min gastric emptying of NaCl (4.13±0.1ml emptied) and sucrose (3.11±0.1ml emptied) compared to control (3.75±0.2 and 2.28±0.1ml emptied, for NaCl and sucrose loads, respectively). In contrast, ICV MK-801 did not alter NaCl emptying (3.82±0.1ml emptied) compared to control (3.82±0.3ml emptied) and actually reduced gastric emptying of sucrose (2.1±0.2 and 2.94±0.1ml 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, since ICV MK-801 failed to increase gastric emptying, these results indicate that MK-801 increases food intake through mechanisms independent of altered gastric emptying.




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