Blockade of hindbrain NMDA receptors containing NR2 subunits increases sucrose intake.
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.
Guard
Douglas B
DB
Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, Univ. Park, PA 16802, USA.
Swartz
Timothy D
TD
Ritter
Robert C
RC
Burns
Gilbert A
GA
Covasa
Mihai
M
D000818:Animals; D020916:Conotoxins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012249:Rhombencephalon / Q000187:drug effects* / Q000378:metabolism; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism; D013395:Sucrose; D013997:Time Factors
D020916:Conotoxins; D018691:Excitatory Amino Acid Antagonists; C533282:N-methyl D-aspartate receptor subtype 2D, rat; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; C432823:NR2C NMDA receptor; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C065286:SDZ EAA 494; D013395:Sucrose; C055407:conotoxin GV