Cooperative interaction between leptin and amylin signaling in the ventral 1 tegmental area for the control of food intake

24 Peripheral co-administration of amylin and leptin produces enhanced suppression of 25 food intake and body weight, but the central nuclei mediating these effects remain 26 unclear. As each of these peptides controls feeding via actions at the ventral 27 tegmental area (VTA), we tested the hypothesis that the VTA is a site of action for 28 the cooperative effects of leptin and amylin on energy balance control. First, we 29 show that intra-VTA injection of amylin and leptin, at doses of each peptide that are 30 effective to reduce food intake and body weight when administered separately, 31 produces an enhanced suppression of feeding when administered in combination. 32 We also demonstrate that subthreshold doses of both amylin and leptin cause 33 significant hypophagia and body weight loss when co-administered into the VTA. 34 Additionally, we provide evidence that VTA amylin receptor blockade significantly 35 attenuates the ability of intra-VTA leptin to reduce feeding and body weight gain. 36 Together, these data provide the first evidence that the VTA mediates the interaction 37 of amylin and leptin to cooperatively promote negative energy balance. 38 39