Amylin receptors in the lateral dorsal tegmental area regulate food intake

University Of Pennsylvania, Philadelphia PA

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Abstract

? DESCRIPTION (provided by applicant): Amylin is a pancreatic-derived hormone that acts in the CNS to reduce food intake. While historically the hypophagic effects of amylin have been attributed to processing by the area postrema, recently the ventral tegmental area (VTA), a nucleus in the mesolimbic reward system, was highlighted as a pharmacologically and physiologically relevant site of action for amylin-mediated control of energy balance and food reward. These discoveries encourage a broader assessment of the CNS circuitry mediating amylin's effects on food intake and reward. Given that the lateral dorsal tegmental area (LDTg) of the brainstem: [1] receives input from feeding-relevant nuclei of the hindbrain and forebrain, [2] binds amylin, and [3] sends input to the VTA to modulate rewarding behavior, the proposed aims will test the hypothesis that amylin receptor signaling in the LDTg is integral for the regulation of energy balance and food reward. Specifically, we will test the physiological requirement of LDTg amylin receptor signaling in regulation of energy balance, the role of LDTg amylin receptor signaling in rewarding value of food, and the potential interaction with gut-to-brain glucagon- like peptide-1 (GLP-1) within-meal satiation signaling as a putative mechanism contributing to intake suppression. Together the proposed aims will highlight the amylin receptor system, as well as LDTg neural processing as critical to the regulation of food intake and food motivated behaviors.