American journal of physiology. Regulatory, integrative and comparative physiologyJun 20, 2014

Signals in a brainstem area reduce hunger and motivation to eat

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 21, 2026

Abstract

Activation of GLP-1 receptors in the hindbrain medial nucleus tractus solitarius (mNTS) reduced food intake and motivated behaviors toward palatable food.

mNTS GLP-1 receptor activation by exendin-4 decreased the intake of a palatable high-fat diet.
Operant responding for sucrose was reduced under a progressive ratio schedule of reinforcement following mNTS GLP-1 receptor stimulation.
A conditioned place preference for a palatable food was diminished with mNTS GLP-1 receptor activation.
These findings suggest that mNTS GLP-1 receptor signaling influences not only satiation but also food reward and motivation.

Simplified

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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Signals in a brainstem area reduce hunger and motivation to eat

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