title: Central melanocortins regulate the motivation for sucrose reward.
abstract: The role of the melanocortin (MC) system in feeding behavior is well established. Food intake is potently suppressed by central infusion of the MC 3/4 receptor agonist α-melanocyte stimulating hormone (α-MSH), whereas the MC 3/4 receptor inverse-agonist Agouti Related Peptide (AGRP) has the opposite effect. MC receptors are widely expressed in both hypothalamic and extra-hypothalamic brain regions, including nuclei involved in food reward and motivation, such as the nucleus accumbens (NAc) and the ventral tegmental area. This suggests that MCs modulate motivational aspects of food intake. To test this hypothesis, rats were injected intracerebroventricularly with α-MSH or AGRP and their motivation for sucrose was tested under a progressive ratio schedule of reinforcement. Food motivated behavior was dose-dependently decreased by α-MSH. Conversely, AGRP increased responding for sucrose, an effect that was blocked by pretreatment with the dopamine receptor antagonist α-flupenthixol. In contrast to progressive ratio responding, free intake of sucrose remained unaltered upon α-MSH or AGRP infusion. In addition, we investigated whether the effects of α-MSH and AGRP on food motivation were mediated by the NAc shell. In situ hybridization of MC3 and MC4 receptor expression confirmed that the MC4 receptor was expressed throughout the NAc, and injection of α-MSH and AGRP into the NAc shell caused a decrease and an increase in motivation for sucrose, respectively. These data show that the motivation for palatable food is modulated by MC4 receptors in the NAc shell, and demonstrate cross-talk between the MC and dopamine system in the modulation of food motivation.
authors: Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Rahul
authors: R
authors: Pandit
authors: Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Esther M
authors: EM
authors: van der Zwaal
authors: Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Mieneke C M
authors: MC
authors: Luijendijk
authors: Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Maike A D
authors: MA
authors: Brans
authors: Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Andrea J
authors: AJ
authors: van Rozen
authors: Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Ralph J A
authors: RJ
authors: Oude Ophuis
authors: Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Animals in Science and Society, Division of Behavioural Neuroscience, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors: Louk J M J
authors: LJ
authors: Vanderschuren
authors: Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Roger A H
authors: RA
authors: Adan
authors: Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Susanne E
authors: SE
authors: la Fleur
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D005247:Feeding Behavior / Q000187:drug effects; D008297:Male; D053486:Melanocortins / Q000378:metabolism*; D009042:Motivation / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017208:Rats, Wistar; D044104:Receptor, Melanocortin, Type 3 / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism; D012201:Reward; D015398:Signal Transduction / Q000187:drug effects; D013395:Sucrose / Q000494:pharmacology*; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D054369:Agouti-Related Protein; D053486:Melanocortins; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D013395:Sucrose; D000521:alpha-MSH