Hypothalamic κ-opioid receptor modulates the orexigenic effect of ghrelin

Romero Picó, Amparo; Vázquez Villar, María Jesús; González Touceda, David; Folgueira Cobos, Cintia; Skibicka, K. P.; Alvarez-Crespo, M.; Van Gestel, M. A.; Velásquez Raimundo, Douglas A.; Schwarzer, C.; Herzog, H.; López Pérez, Miguel A.; Adan, R. A.; Dickson, S. L.; Diéguez González, Carlos; Nogueiras Pozo, Rubén
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URI: http://hdl.handle.net/20.500.11940/2087
PMID: 23348063
ISSN: 0893-133X
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Date issued
2013
Journal title
NEUROPSYCHOPHARMACOLOGY
Type of content
Artigo
MeSH
Agouti-Related Protein | Animals | Arcuate Nucleus of Hypothalamus | Conditioning, Operant | Drug Interactions | Eating | Enkephalins | Gene Silencing | Ghrelin | Infusions, Intraventricular | Intracellular Signaling Peptides and Proteins | Male | Microinjections | Narcotic Antagonists | Neuropeptide Y/metabolism | Neuropeptides | Orexins | Protein Precursors | Rats | Receptors, Ghrelin | Receptors, Opioid, kappa | Reinforcement Schedule | Signal Transduction | Ventral Tegmental Area
Abstract
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 ?-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.