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Int. J. Mol. Sci. 2017, 18(5), 914; doi:10.3390/ijms18050914

Exploring the Behavioral and Metabolic Phenotype Generated by Re-Introduction of the Ghrelin Receptor in the Ventral Tegmental Area

1
Section for Metabolic Receptology, The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark
2
Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
3
Center for Neuroscience, University of Copenhagen, 2200 Copenhagen, Denmark
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Katalin Prokai-Tatrai
Received: 22 February 2017 / Revised: 1 April 2017 / Accepted: 20 April 2017 / Published: 26 April 2017
(This article belongs to the Special Issue Neurobiological Perspectives on Ghrelin)
View Full-Text   |   Download PDF [3462 KB, uploaded 26 April 2017]   |  

Abstract

Ghrelin receptor (Ghr-R) signaling in neurons of the ventral tegmental area (VTA) can modulate dopaminergic function and the reward-related effects of both palatable foods and drugs of abuse. In this study, we re-introduced the Ghr-R in VTA neurons in Ghr-R knockout mice (Ghr-RVTA mice) to specifically study the importance of the constitutively active Ghr-R for VTA neuronal signaling. Our results showed that re-introduction of the Ghr-R in the VTA had no impact on body weight or food intake under basal conditions. However, during novel environment stress Ghr-RVTA mice showed increased food intake and energy expenditure compared to Ghr-R knockout mice, demonstrating the significance of Ghr-R signaling in the response to stress. Ghr-RVTA mice also showed increased cocaine-induced locomotor activity compared to Ghr-R knockout mice, highlighting the importance of ghrelin signaling for the reward-related effects of activation of VTA neurons. Overall, our data suggest that re-introduction of the Ghr-R in the mesolimbic reward system of Ghr-R knockout mice increases the level of activation induced by both cocaine and novelty stress. View Full-Text
Keywords: ghrelin; ghrelin receptor; ventral tegmental area; energy expenditure; food anticipatory activity; stress; cocaine sensitivity ghrelin; ghrelin receptor; ventral tegmental area; energy expenditure; food anticipatory activity; stress; cocaine sensitivity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Skov, L.J.; Jensen, M.; Christiansen, S.H.; Ratner, C.; Woldbye, D.P.D.; Holst, B. Exploring the Behavioral and Metabolic Phenotype Generated by Re-Introduction of the Ghrelin Receptor in the Ventral Tegmental Area. Int. J. Mol. Sci. 2017, 18, 914.

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