Effect of MTII on food intake and brain c-Fos in melanocortin-3, melanocortin-4, and double MC3 and MC4 receptor knockout mice

Autor: Amy Andreasen, Neil E. Rowland, Carrie Haskell-Luevano, Kimberly L. Robertson, Jay W. Schaub
Rok vydání: 2010
Předmět:
Zdroj: Peptides. 31(12)
ISSN: 1873-5169
Popis: 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.
Databáze: OpenAIRE