NMDA-type glutamate receptors participate in reduction of food intake following hindbrain melanocortin receptor activation.
Hindbrain injection of a melanocortin-3/4 receptor agonist, MTII, reduces food intake primarily by reducing meal size. Our previously reported results indicate that N-methyl-D-aspartate-type glutamate receptors (NMDAR) in the nucleus of the solitary tract (NTS) play an important role in the control of meal size and food intake. Therefore, we hypothesized that activation of NTS NMDARs contribute to reduction of food intake in response to fourth ventricle or NTS injection of MTII. We found that coinjection of a competitive NMDAR antagonist (d-CPP-ene) with MTII into the fourth ventricle or directly into the NTS of adult male rats attenuated MTII-induced reduction of food intake. Hindbrain NMDAR antagonism also attenuated MTII-induced ERK1/2 phosphorylation in NTS neurons and prevented synapsin I phosphorylation in central vagal afferent endings, both of which are cellular mechanisms previously shown to participate in hindbrain melanocortinergic reduction of food intake. Together, our results indicate that NMDAR activation significantly contributes to reduction of food intake following hindbrain melanocortin receptor activation, and it participates in melanocortinergic signaling in NTS neural circuits that mediate reduction of food intake.
Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, Washington.
Carlos A
CA
Campos
Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, Washington britter@vetmed.wsu.edu.
Robert C
RC
Ritter
D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D004435:Eating / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D007276:Injections, Intraventricular; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D044101:Receptors, Melanocortin / Q000819:agonists* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012249:Rhombencephalon / Q000187:drug effects* / Q000378:metabolism; D012527:Satiation; D015398:Signal Transduction / Q000187:drug effects; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism; D016704:Synapsins / Q000378:metabolism; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives*
D018691:Excitatory Amino Acid Antagonists; D044101:Receptors, Melanocortin; D016194:Receptors, N-Methyl-D-Aspartate; D016704:Synapsins; C105974:acetyl-norleucyl(4)-(aspartyl(5)-histidyl(6)-phenylalanyl(7)-arginyl(8)-tryptophyl(9)-lysyl(10))cyclo-alpha-MSH(4-10)amide; D000521:alpha-MSH; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
nucleus of the solitary tract; proopiomelanocortin; satiation; vagus