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1 Nutritional Sciences, College of Health and Human Development, Pennsylvania State University, University Park, PA, USA
2 Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA, USA
* To whom correspondence should be addressed. E-mail: mzc13{at}psu.edu.
Systemic injection of MK-801, a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptor ion channels, increases meal size and delays satiation. We examined whether MK-801 increases food intake by directly interfering with actions of cholecystokinin (CCK). Prior administration of MK-801 (100 µg/kg, IP) reversed the inhibitory effects of CCK-8 (2 and 4 µg/kg, IP) on real feeding of both liquid and solid foods. MK-801 alone did not alter 30-min sham intake of 15% sucrose, compared with intake after saline. Furthermore, while CCK-8 (2 or 4 µg/kg, IP) reduced sham intake, this reduction was not attenuated by MK-801 pre-treatment. To ascertain whether MK-801 attenuation of CCK-induced reduction of real feeding was associated with attenuated inhibition of gastric emptying, we tested the effect of MK-801 pre-treatment on CCK-induced inhibition of gastric emptying of 5-ml saline loads. Ten-min gastric emptying was accelerated after MK-801 (3.9 ±0.2 ml) compared to saline vehicle (2.72 ± 0.2 ml). CCK-8 (0.5 µg/kg, IP) reduced 10-min emptying to 1.36 ± 0.3 ml. Pre-treatment with MK-801 did not significantly attenuate CCK-8-induced reduction of gastric emptying (0.9 ± 0.4 ml). This series of experiments demonstrate that blockade of NMDA ion channels reverses inhibition of real feeding by CCK. However, neither inhibition of sham feeding nor inhibition of gastric emptying by CCK is attenuated by MK-801. Therefore, increased food intake following NMDA receptor blockade is not caused by a direct interference with CCK-induced satiation. Rather, increased real feeding, either in the presence or absence of CCK, depends on blockade of NMDA receptor participation in other post-oral feedback signals such as gastric sensation or gastric tone.
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