The Glucagon-Like Peptide 1 (GLP-1) Analogue, Exendin-4, Decreases the Rewarding Value of Food: A New Role for Mesolimbic GLP-1 Receptors
| Autor: | Karolina P. Skibicka, Suzanne L. Dickson, Caroline Hansson, Hans Nissbrandt, Rozita H. Shirazi, Filip Bergquist |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Agonist
Male endocrine system medicine.drug_class Stimulation Glucagon-Like Peptide-1 Receptor Diabetes Mellitus Experimental Rats Sprague-Dawley 03 medical and health sciences Reward system Eating 0302 clinical medicine Reward Glucagon-Like Peptide 1 medicine Limbic System Receptors Glucagon Glucose homeostasis Animals Receptor 030304 developmental biology 0303 health sciences Venoms General Neuroscience digestive oral and skin physiology Lizards Articles Glucagon-like peptide-1 Conditioned place preference Rats Infusions Intraventricular Food Conditioning Operant Exenatide Brain stimulation reward Psychology Peptides Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuroscience; Vol 32 |
| ISSN: | 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.6326-11.2012 |
| Popis: | The glucagon-like peptide 1 (GLP-1) system is a recently established target for type 2 diabetes treatment. In addition to regulating glucose homeostasis, GLP-1 also reduces food intake. Previous studies demonstrate that the anorexigenic effects of GLP-1 can be mediated through hypothalamic and brainstem circuits which regulate homeostatic feeding. Here, we demonstrate an entirely novel neurobiological mechanism for GLP-1-induced anorexia in rats, involving direct effects of a GLP-1 agonist, Exendin-4 (EX4) on food reward that are exerted at the level of the mesolimbic reward system. We assessed the impact of peripheral, central, and intramesolimbic EX4 on two models of food reward: conditioned place preference (CPP) and progressive ratio operant-conditioning. Food-reward behavior was reduced in the CPP test by EX4, as rats no longer preferred an environment previously paired to chocolate pellets. EX4 also decreased motivated behavior for sucrose in a progressive ratio operant-conditioning paradigm when administered peripherally. We show that this effect is mediated centrally, via GLP-1 receptors (GLP-1Rs). GLP-1Rs are expressed in several key nodes of the mesolimbic reward system; however, their function remains unexplored. Thus we sought to determine the neurobiological substrates underlying the food-reward effect. We found that the EX4-mediated inhibition of food reward could be driven from two key mesolimbic structures—ventral tegmental area and nucleus accumbens—without inducing concurrent malaise or locomotor impairment. The current findings, that activation of central GLP-1Rs strikingly suppresses food reward/motivation by interacting with the mesolimbic system, indicate an entirely novel mechanism by which the GLP-1R stimulation affects feeding-oriented behavior. |
| Databáze: | OpenAIRE |
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