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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/R921    most recent 90456.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Guard, D. B. Articles by Covasa, M. Search for Related Content PubMed PubMed Citation Articles by Guard, D. B. Articles by Covasa, M.

APPETITE, OBESITY, AND DIGESTION

Blockade of hindbrain NMDA receptors containing NR2 subunits increases sucrose intake

¹Physiology Interdepartmental Graduate Program, Huck Institutes of Life Sciences and ²Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, Pennsylvania; ³Department of Veterinary Comparative Anatomy Pharmacology and Physiology, Program in Neuroscience, Washington State University, Pullman, Washington; and ⁴School of Veterinary Medicine, Ross University, St. Kitts

Submitted 28 May 2008 ; accepted in final form 2 February 2009

We have previously shown that blockade of N-methyl-D-aspartate (NMDA) receptors in the caudal brain stem delays satiation and increases food intake. NMDA receptors are heterodimers made up of distinct, but different, ion channel subunits. The NR2 subunits of the NMDA receptor contain the binding site for glutamate. About half of vagal afferents express immunoreactivity for NMDA NR2B subunit and about half of the NR2B expressing afferents also express NMDA NR2C or NR2D subunits. This suggests that increased food intake may be evoked by interference with glutamate binding to NMDA channels containing the NR2B subunit. To test this, we measured deprivation-induced intake of 15% sucrose solution following fourth ventricle and intra-nucleus of the solitary tract (intra-NTS) injections of Conantokin G (Con G; NR2B blocker), D-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphoric acid (D-CPPene; NR2B/2A blocker), and (±)-cis-1-(phenanthren-2yl-carbonyl)piperazine-2,3-dicarboxylic acid (PPDA; NR2D/C blocker). Fourth ventricular administration of Con G (5, 20, 40, 80 ng), D-CPPene (3.0, 6.25, 12.5, 25, 50, 100 ng), and PPDA (300, 400 ng) increased sucrose intake significantly compared with control. Likewise, injections of Con G (10 ng), D-CPPene (5 ng, 10 ng), and PPDA (0.5, 1.0, 2.5, 5.0 ng) directly into the NTS significantly increased sucrose intake. These results show that hindbrain injection of competitive NMDA antagonists with selectivity or preference for the NMDA receptor NR2B or NR2C subunits increases food intake.

satiation; vagal afferents; glutamate