Keen-Rhinehart E, Bartness TJ. Leptin inhibits food-deprivation-induced increases in food intake and food hoarding. Am J Physiol Regul Integr Comp Physiol 295: R1737-R1746, 2008. First published October 1, 2008 doi:10.1152/ajpregu.90512.2008.-Food deprivation stimulates foraging and hoarding and to a much lesser extent, food intake in Siberian hamsters. Leptin, the anorexigenic hormone secreted primarily from adipocytes, may act in the periphery, the brain, or both to inhibit these ingestive behaviors. Therefore, we tested whether leptin given either intracerebroventricularly or intraperitoneally, would block food deprivation-induced increases in food hoarding, foraging, and intake in animals with differing foraging requirements. Hamsters were trained in a running wheel-based food delivery foraging system coupled with simulated burrow housing. We determined the effects of food deprivation and several peripheral doses of leptin on plasma leptin concentrations. Hamsters were then food deprived for 48 h and given leptin (0, 10, 40, or 80 g ip), and additional hamsters were food deprived for 48 h and given leptin (0, 1.25, 2.5, or 5.0 g icv). Foraging, food intake, and hoarding were measured postinjection. Food deprivation stimulated food hoarding to a greater degree and duration than food intake. In animals with a foraging requirement, intracerebroventricular leptin almost completely blocked food deprivation-induced increased food hoarding and intake, but increased foraging. Peripheral leptin treatment was most effective in a sedentary control group, completely inhibiting food deprivation-induced increased food hoarding and intake at the two highest doses, and did not affect foraging at any dose. Thus, the ability of leptin to inhibit food deprivation-induced increases in ingestive behaviors differs based on foraging effort (energy expenditure) and the route of administration of leptin administration. foraging; wheel running; feeding; hypothalamus; Siberian hamsters OBESITY IS A DISEASE OF, literally and figuratively, enormous proportions. As of yet, there are currently no effective treatments for obesity, and this disease continues to run rampant throughout developed and underdeveloped countries. Therefore, innovative and alternative lines of basic research are needed to forge the beginnings of pathways to new potential obesity treatments. One critical area of basic research involves determining the neuroendocrine factors that regulate ingestive behavior. Often ingestive behavior is thought of in terms of food intake only, but it is important to consider the entire sequence of events associated with food, and this includes two phases: 1) the acquisition and storage of food or the appetitive phase and 2) the actual eating of the food or the consummatory phase (20). The consummatory aspects of ingestive behavior have received the most attention in the quest to understand the energy intake portion of the obesity phenomenon. As for the appetitive phase of ingestive behavior, consisting of foraging and food hoarding,...