Effect of MTII on food intake and brain c-Fos in melanocortin-3, melanocortin-4, and double MC3 and MC4 receptor knockout mice.
Mice with genomic knockout of either melanocortin type 3 receptors (MC3R-/-), type 4 receptors (MC4R-/-) or knockout of both (double knockout, DKO) were tested for their anorectic response to the mixed MC3/4R agonist, MTII, injected into the anterior cerebral ventricle. Wild type (WT) mice showed a strong anorexia and, as expected, DKO were completely unresponsive to MTII. In contrast, both MC3R-/- and MC4R-/- showed a partial anorectic response. Induction of c-Fos immunoreactivity by MTII was examined in brain regions including paraventricular hypothalamus (PVN) and area postrema (AP). Compared with WT, MC4R-/- showed no activation in AP but showed normal activation in PVN, whereas MC3R-/- showed reduced activation in PVN but not in AP. RT-PCR analysis showed that hypothalamic mRNA for MC3R in MC4R-/- and for MC4R in MC3R-/- was unaltered from WT levels. These data suggest that both receptor subtypes are involved in the behavioral action of MTII, and that the critical receptors are in different brain regions.
Rowland
Neil E
NE
Department of Psychology, University of Florida, Gainesville, FL 32611-2250, United States. nrowland@ufl.edu
Schaub
Jay W
JW
Robertson
Kimberly L
KL
Andreasen
Amy
A
Haskell-Luevano
Carrie
C
D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000378:metabolism; D031608:Area Postrema / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D044104:Receptor, Melanocortin, Type 3 / Q000819:agonists* / Q000235:genetics; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists* / Q000235:genetics; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000494:pharmacology
D016760:Proto-Oncogene Proteins c-fos; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; 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
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