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Hypothalamic κ-Opioid Receptor Modulates the Orexigenic Effect of Ghrelin.

Journal article
Authors Amparo Romero-Picó
Maria J Vázquez
David González-Touceda
Cintia Folgueira
Karolina P Skibicka
Mayte Alvarez-Crespo
Margriet A Van Gestel
Douglas A Velásquez
Christoph Schwarzer
Herbert Herzog
Miguel López
Roger A. H. Adan
Suzanne L. Dickson
Carlos Diéguez
Rubén Nogueiras
Published in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Volume 38
Issue 7
Pages 1296-307
ISSN 1740-634X
Publication year 2013
Published at Institute of Neuroscience and Physiology, Department of Physiology
Pages 1296-307
Language en
Keywords ghrelin, food intake, appetite, dopamine, opioid
Subject categories Neurophysiology, Neurobiology, Neurochemistry, Neuroscience, Neurobiology


The opioid system is well recognized as an important regulator of appetite and energy balance. We now hypothesized that the hypothalamic opioid system might modulate the orexigenic effect of ghrelin. Using pharmacological and gene silencing approaches, we demonstrate that ghrelin utilizes a hypothalamic κ-opioid receptor (KOR) pathway to increase food intake in rats. Pharmacological blockade of KOR decreases the acute orexigenic effect of ghrelin. Inhibition of KOR expression in the hypothalamic arcuate nucleus is sufficient to blunt ghrelin-induced food intake. By contrast, the specific inhibition of KOR expression in the ventral tegmental area does not affect central ghrelin-induced feeding. This new pathway is independent of ghrelin-induced AMP-activated protein kinase activation, but modulates the levels of the transcription factors and orexigenic neuropeptides triggered by ghrelin to finally stimulate feeding. Our novel data implicate hypothalamic KOR signaling in the orexigenic action of ghrelin.

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