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dc.contributor.authorFernø, Johaneng
dc.contributor.authorVarela, Luiseng
dc.contributor.authorSkrede, Siljeeng
dc.contributor.authorVázquez, María Jesúseng
dc.contributor.authorNogueiras, Rubéneng
dc.contributor.authorDiéguez, Carloseng
dc.contributor.authorVidal-Puig, Antonioeng
dc.contributor.authorSteen, Vidar Martineng
dc.contributor.authorLópez, Migueleng
dc.date.accessioned2012-02-27T13:22:44Z
dc.date.available2012-02-27T13:22:44Z
dc.date.issued2011-06-13eng
dc.identifier.citationPLoS ONE 6(6): e20571en
dc.identifier.issn1932-6203eng
dc.identifier.urihttp://hdl.handle.net/1956/5645
dc.description.abstractThe success of antipsychotic drug treatment in patients with schizophrenia is limited by the propensity of these drugs to induce hyperphagia, weight gain and other metabolic disturbances, particularly evident for olanzapine and clozapine. However, the molecular mechanisms involved in antipsychotic-induced hyperphagia remain unclear. Here, we investigate the effect of olanzapine administration on the regulation of hypothalamic mechanisms controlling food intake, namely neuropeptide expression and AMP-activated protein kinase (AMPK) phosphorylation in rats. Our results show that subchronic exposure to olanzapine upregulates neuropeptide Y (NPY) and agouti related protein (AgRP) and downregulates proopiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC). This effect was evident both in rats fed ad libitum and in pair-fed rats. Of note, despite weight gain and increased expression of orexigenic neuropeptides, subchronic administration of olanzapine decreased AMPK phosphorylation levels. This reduction in AMPK was not observed after acute administration of either olanzapine or clozapine. Overall, our data suggest that olanzapine-induced hyperphagia is mediated through appropriate changes in hypothalamic neuropeptides, and that this effect does not require concomitant AMPK activation. Our data shed new light on the hypothalamic mechanism underlying antipsychotic-induced hyperphagia and weight gain, and provide the basis for alternative targets to control energy balance.en
dc.language.isoengeng
dc.publisherPublic Library of Scienceeng
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/eng
dc.titleOlanzapine-Induced Hyperphagia and Weight Gain Associate with Orexigenic Hypothalamic Neuropeptide Signaling without Concomitant AMPK Phosphorylationeng
dc.typePeer reviewedeng
dc.typeJournal articleeng
dc.subject.nsiVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Psychiatry, child psychiatry: 757eng
dc.rights.holderCopyright 2011 Fernø¸ et al.
dc.type.versionpublishedVersioneng
bora.peerreviewedPeer reviewedeng
bibo.doihttp://dx.doi.org/10.1371/journal.pone.0020571eng
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0020571


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