Abstract

Central glucagon-like-peptide-1 (GLP-1) receptor activation reduces food intake; however, brain nuclei and mechanism(s) mediating this effect remain poorly understood. Although central nervous system GLP-1 is produced almost exclusively in the nucleus of the solitary tract in the hindbrain, GLP-1 receptors (GLP-1R) are expressed throughout the brain, including nuclei in the mesolimbic reward system (MRS), e.g. the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Here, we examine the MRS as a potential site of action for GLP-1-mediated control of food intake and body weight. Double immunohistochemistry for Fluorogold (monosynaptic retrograde tracer) and GLP-1 neuron immunoreactivity indicated that GLP-1-producing nucleus tractus solitarius neurons project directly to the VTA, the NAc core, and the NAc shell. Pharmacological data showed that GLP-1R activation in the VTA, NAc core, and NAc shell decreased food intake, especially of highly-palatable foods, and body weight. Moreover, blockade of endogenous GLP-1R signaling in the VTA and NAc core resulted in a significant increase in food intake, establishing a physiological relevance for GLP-1 signaling in the MRS. Current data highlight these nuclei within the MRS as novel sites for GLP-1R-mediated control of food intake and body weight.