Melanocortin 3 Receptor Signaling in Midbrain Dopamine Neurons Increases the Motivation for Food Reward

Rahul Pandit, Azar Omrani, Mieneke C M Luijendijk, Véronne A J de Vrind, Andrea J. van Rozen, Ralph J A Oude Ophuis, Keith Garner, I. Kalló, Alexander Ghanem, Z. Liposits, Karl Klaus Conzelmann, Louk J M J Vanderschuren, Susanne E. la Fleur, Roger A H Adan

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.Neuropsychopharmacology advance online publication, 2 March 2016; doi:10.1038/npp.2016.19.

Original languageEnglish
JournalNeuropsychopharmacology
DOIs
Publication statusAccepted/In press - Feb 8 2016

Fingerprint

Receptor, Melanocortin, Type 3
Ventral Tegmental Area
Dopaminergic Neurons
Mesencephalon
Reward
Motivation
Melanocyte-Stimulating Hormones
Food
Receptor, Melanocortin, Type 4
Sucrose
Eating
Flupenthixol
Melanocortins
Satiation
Reinforcement Schedule
Food Preferences
Dopamine Agents
Arcuate Nucleus of Hypothalamus
Dopamine Antagonists
Feeding Behavior

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Pandit, R., Omrani, A., Luijendijk, M. C. M., de Vrind, V. A. J., van Rozen, A. J., Ophuis, R. J. A. O., ... Adan, R. A. H. (Accepted/In press). Melanocortin 3 Receptor Signaling in Midbrain Dopamine Neurons Increases the Motivation for Food Reward. Neuropsychopharmacology. https://doi.org/10.1038/npp.2016.19

Melanocortin 3 Receptor Signaling in Midbrain Dopamine Neurons Increases the Motivation for Food Reward. / Pandit, Rahul; Omrani, Azar; Luijendijk, Mieneke C M; de Vrind, Véronne A J; van Rozen, Andrea J.; Ophuis, Ralph J A Oude; Garner, Keith; Kalló, I.; Ghanem, Alexander; Liposits, Z.; Conzelmann, Karl Klaus; Vanderschuren, Louk J M J; la Fleur, Susanne E.; Adan, Roger A H.

In: Neuropsychopharmacology, 08.02.2016.

Research output: Contribution to journalArticle

Pandit, R, Omrani, A, Luijendijk, MCM, de Vrind, VAJ, van Rozen, AJ, Ophuis, RJAO, Garner, K, Kalló, I, Ghanem, A, Liposits, Z, Conzelmann, KK, Vanderschuren, LJMJ, la Fleur, SE & Adan, RAH 2016, 'Melanocortin 3 Receptor Signaling in Midbrain Dopamine Neurons Increases the Motivation for Food Reward', Neuropsychopharmacology. https://doi.org/10.1038/npp.2016.19
Pandit, Rahul ; Omrani, Azar ; Luijendijk, Mieneke C M ; de Vrind, Véronne A J ; van Rozen, Andrea J. ; Ophuis, Ralph J A Oude ; Garner, Keith ; Kalló, I. ; Ghanem, Alexander ; Liposits, Z. ; Conzelmann, Karl Klaus ; Vanderschuren, Louk J M J ; la Fleur, Susanne E. ; Adan, Roger A H. / Melanocortin 3 Receptor Signaling in Midbrain Dopamine Neurons Increases the Motivation for Food Reward. In: Neuropsychopharmacology. 2016.
@article{96a0af7c0f9c4f3aaac88eb32b158213,
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.Neuropsychopharmacology advance online publication, 2 March 2016; doi:10.1038/npp.2016.19.",
author = "Rahul Pandit and Azar Omrani and Luijendijk, {Mieneke C M} and {de Vrind}, {V{\'e}ronne A J} and {van Rozen}, {Andrea J.} and Ophuis, {Ralph J A Oude} and Keith Garner and I. Kall{\'o} and Alexander Ghanem and Z. Liposits and Conzelmann, {Karl Klaus} and Vanderschuren, {Louk J M J} and {la Fleur}, {Susanne E.} and Adan, {Roger A H}",
year = "2016",
month = "2",
day = "8",
doi = "10.1038/npp.2016.19",
language = "English",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Melanocortin 3 Receptor Signaling in Midbrain Dopamine Neurons Increases the Motivation for Food Reward

AU - Pandit, Rahul

AU - Omrani, Azar

AU - Luijendijk, Mieneke C M

AU - de Vrind, Véronne A J

AU - van Rozen, Andrea J.

AU - Ophuis, Ralph J A Oude

AU - Garner, Keith

AU - Kalló, I.

AU - Ghanem, Alexander

AU - Liposits, Z.

AU - Conzelmann, Karl Klaus

AU - Vanderschuren, Louk J M J

AU - la Fleur, Susanne E.

AU - Adan, Roger A H

PY - 2016/2/8

Y1 - 2016/2/8

N2 - 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.Neuropsychopharmacology advance online publication, 2 March 2016; doi:10.1038/npp.2016.19.

AB - 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.Neuropsychopharmacology advance online publication, 2 March 2016; doi:10.1038/npp.2016.19.

UR - http://www.scopus.com/inward/record.url?scp=84959575534&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959575534&partnerID=8YFLogxK

U2 - 10.1038/npp.2016.19

DO - 10.1038/npp.2016.19

M3 - Article

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

ER -