title: Melanocortin 3 Receptor Signaling in Midbrain Dopamine Neurons Increases the Motivation for Food Reward.
abstract: The central melanocortin (MC) system mediates its effects on food intake via MC3 (MC3R) and MC4 receptors (MC4R). Although the role of MC4R in meal size determination, satiation, food preference, and motivation is well established, the involvement of MC3R in the modulation of food intake has been less explored. Here, we investigated the role of MC3R on the incentive motivation for food, which is a crucial component of feeding behavior. Dopaminergic neurons within the ventral tegmental area (VTA) have a crucial role in the motivation for food. We here report that MC3Rs are expressed on VTA dopaminergic neurons and that pro-opiomelanocortinergic (POMC) neurons in the arcuate nucleus of the hypothalamus (Arc) innervate these VTA dopaminergic neurons. Our findings show that intracerebroventricular or intra-VTA infusion of the selective MC3R agonist γMSH increases responding for sucrose under a progressive ratio schedule of reinforcement, but not free sucrose consumption in rats. Furthermore, ex vivo electrophysiological recordings show increased VTA dopaminergic neuronal activity upon γMSH application. Consistent with a dopamine-mediated effect of γMSH, the increased motivation for sucrose after intra-VTA infusion of γMSH was blocked by pretreatment with the dopamine receptor antagonist α-flupenthixol. Taken together, we demonstrate an Arc POMC projection onto VTA dopaminergic neurons that modulates motivation for palatable food via activation of MC3R signaling.
authors: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Rahul
authors: R
authors: Pandit
authors: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Azar
authors: A
authors: Omrani
authors: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Mieneke C M
authors: MC
authors: Luijendijk
authors: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Véronne A J
authors: VA
authors: de Vrind
authors: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Andrea J
authors: AJ
authors: Van Rozen
authors: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Ralph J A Oude
authors: RJ
authors: Ophuis
authors: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Keith
authors: K
authors: Garner
authors: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors: Imre
authors: I
authors: Kallo
authors: Center for Integrative Protein Science, Department of Chemistry, Ludwig-Maximilians University München, Munich, Germany.
authors: Alexander
authors: A
authors: Ghanem
authors: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors: Zsolt
authors: Z
authors: Liposits
authors: Center for Integrative Protein Science, Department of Chemistry, Ludwig-Maximilians University München, Munich, Germany.
authors: Karl-Klaus
authors: KK
authors: Conzelmann
authors: 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 Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Susanne E
authors: SE
authors: la Fleur
authors: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Roger A H
authors: RA
authors: Adan
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology / Q000502:physiology*; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior; D005502:Food; D008297:Male; D009042:Motivation; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D017208:Rats, Wistar; D044104:Receptor, Melanocortin, Type 3 / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D012201:Reward; D015398:Signal Transduction; D013395:Sucrose / Q000008:administration & dosage; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019825:gamma-MSH / Q000008:administration & dosage
chemical_list: D044104:Receptor, Melanocortin, Type 3; D019825:gamma-MSH; C514973:melanocortin 3 receptor, rat; D013395:Sucrose; D011333:Pro-Opiomelanocortin