Hindbrain nucleus tractus solitarius glucagon-like peptide-1 receptor signaling reduces appetitive and motivational aspects of feeding

AL Alhadeff, HJ Grill - American Journal of Physiology …, 2014 - journals.physiology.org
American Journal of Physiology-Regulatory, Integrative and …, 2014journals.physiology.org
Central glucagon-like peptide-1 receptor (GLP-1R) signaling reduces food intake by
affecting a variety of neural processes, including those mediating satiation, motivation, and
reward. While the literature suggests that separable neurons and circuits control these
processes, this notion has not been adequately investigated. The intake inhibitory effects of
GLP-1R signaling in the hindbrain medial nucleus tractus solitarius (mNTS) have been
attributed to interactions with vagally transmitted gastrointestinal satiation signals that are …
Central glucagon-like peptide-1 receptor (GLP-1R) signaling reduces food intake by affecting a variety of neural processes, including those mediating satiation, motivation, and reward. While the literature suggests that separable neurons and circuits control these processes, this notion has not been adequately investigated. The intake inhibitory effects of GLP-1R signaling in the hindbrain medial nucleus tractus solitarius (mNTS) have been attributed to interactions with vagally transmitted gastrointestinal satiation signals that are also processed by these neurons. Here, behavioral and pharmacological techniques are used to test the novel hypothesis that the reduction of food intake following mNTS GLP-1R stimulation also results from effects on food-motivated appetitive behaviors. Results show that mNTS GLP-1R activation by microinjection of exendin-4, a long-acting GLP-1R agonist, reduced 1) intake of a palatable high-fat diet, 2) operant responding for sucrose under a progressive ratio schedule of reinforcement and 3) the expression of a conditioned place preference for a palatable food. Together, these data demonstrate that the intake inhibitory effects of mNTS GLP-1R signaling extend beyond satiation and include effects on food reward and motivation that are typically ascribed to midbrain and forebrain neurons.
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