MTII attenuates ghrelin- and food deprivation-induced increases in food hoarding and food intake.
Food deprivation triggers a constellation of physiological and behavioral changes including increases in peripherally-produced ghrelin and centrally-produced agouti-related protein (AgRP). Upon refeeding, food intake is increased in most species, however hamsters primarily increase food hoarding. Food deprivation-induced increases in food hoarding by Siberian hamsters are mimicked by peripheral ghrelin and central AgRP injections. Because food deprivation stimulates ghrelin as well as AgRP synthesis/release, food deprivation-induced increases in hoarding may be mediated by melanocortin 3 or 4 receptor (MC3/4-R) antagonism via AgRP, the MC3/4-R inverse agonist. Therefore, we asked: Can a MC3/4-R agonist block food deprivation- or ghrelin-induced increases in foraging, food hoarding and food intake? This was accomplished by injecting melanotan II (MTII), a synthetic MC3/4-R agonist, into the 3rd ventricle in food deprived, fed or peripheral ghrelin injected hamsters and housed in a running wheel-based food delivery foraging system. Three foraging conditions were used: a) no running wheel access, non-contingent food, b) running wheel access, non-contingent food or c) a foraging requirement for food (10 revolutions/pellet). Food deprivation was a more potent stimulator of foraging and hoarding than ghrelin. Concurrent injections of MTII completely blocked food deprivation- and ghrelin-induced increases in food intake and attenuated, but did not always completely block, food deprivation- and ghrelin-induced increases in food hoarding. Collectively, these data suggest that the MC3/4-R are involved in ghrelin- and food deprivation-induced increases in food intake, but other neurochemical systems, such as previously demonstrated with neuropeptide Y, also are involved in increases in food hoarding as well as foraging.
Keen-Rhinehart
Erin
E
Department of Biology and Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA 30302-4010, USA.
Bartness
Timothy J
TJ
D000818:Animals; D001066:Appetite / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D006224:Cricetinae; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005508:Food Deprivation / Q000502:physiology*; D054439:Ghrelin / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*; D017111:Phodopus; D044104:Receptor, Melanocortin, Type 3 / Q000502:physiology; D044105:Receptor, Melanocortin, Type 4 / Q000502:physiology; D012420:Running / Q000502:physiology; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology