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dc.creatorSilva-Moreno, Arturo
dc.creatorGonzález-Espinosa, Claudia
dc.creatorLeón-Olea, Martha
dc.creatorCruz, Silvia L.
dc.date.accessioned2017-06-30T02:06:09Z
dc.date.available2017-06-30T02:06:09Z
dc.date.issued2012es_ES
dc.identifier1526es_ES
dc.identifier.issn0014-2999es_ES
dc.identifier.urihttp://repositorio.inprf.gob.mx/handle/123456789/6205
dc.identifier.urihttps://doi.org/10.1016/j.ejphar.2011.10.034es_ES
dc.language.isoenges_ES
dc.relation674 (2-3) 239-247 p.es_ES
dc.relationversión del editores_ES
dc.rightsacceso cerradoes_ES
dc.titleSynergistic antinociceptive actions and tolerance development produced by morphine-fentanyl coadministration: correlation with _-opioid receptor internalizationes_ES
dc.typearticlees_ES
dc.contributor.affiliationDepartamento de Farmacobiología, Cinvestav, Sede Sur. Calzada de Tenorios # 235, Col. Granjas Coapa, México DF, 14330, México.es_ES
dc.contributor.emailslcruz@cinvestav.mxes_ES
dc.relation.jnabreviadoEUR J PHARMACOLes_ES
dc.relation.journalEuropean Journal of Pharmacologyes_ES
dc.identifier.placePaíses Bajoses_ES
dc.date.published2012es_ES
dc.identifier.organizacionInstituto Nacional de Psiquiatría Ramón de la Fuente Muñizes_ES
dc.identifier.eissn1879-0712es_ES
dc.identifier.doi10.1016/j.ejphar.2011.10.034es_ES
dc.description.monthEnees_ES
dc.description.abstractotrodiomaIt has been described that coadministration of opioids with low doses of other analgesics can reduce adverse effects and increase antinociception, but combinations of two _-opioid receptor agonists have been poorly explored. The objective of this work was threefold: 1) to evaluate the antinociceptive combination of i.c.v. morphine and fentanyl at different doses; 2) to compare the antinociception produced by acute or repeated administration of an effective morphine dose (1 _g) alone, or combined with a low fentanyl dose (1 ng); and 3) to correlate these effects with _-opioid receptor internalization in periaqueductal gray matter and locus coeruleus. Antinociception was evaluated by the tail-flick test and receptor internalization was analyzed by confocal microscopy in Wistar rats. Drug interactions were examined by administering combinations of opioids in 1:3, 1:1 and 3:1 ratios of their respective ED(50) fractions. For tolerance and internalization studies, animals were i.c.v. injected only once (acute treatment) or twice a day until five administrations were completed. Our results show that morphine and fentanyl have synergistic effects. The combination of 1 ng fentanyl with 1 _g morphine increases the magnitude and duration of antinociception not only after a single injection, but also after five administrations when tolerance develops to morphine alone. Increased and long-lasting antinociception correlates positively with increased _-arrestin 2 activity and _-opioid receptor internalization in periaqueductal gray matter and locus coeruleus. These results suggest that combined administration of morphine and fentanyl increases long-lasting antinociception and _-arrestin 2 signaling contributes to the combination effectses_ES
dc.subject.koAnalgesics, Opioides_ES
dc.subject.koadministration & dosagees_ES
dc.subject.koAnalgesics, Opioides_ES
dc.subject.kopharmacologyes_ES
dc.subject.koAnimalses_ES
dc.subject.koArrestinses_ES
dc.subject.kometabolismes_ES
dc.subject.koDose-Response Relationship, Druges_ES
dc.subject.koDrug Synergismes_ES
dc.subject.koDrug Tolerancees_ES
dc.subject.koEndocytosises_ES
dc.subject.kodrug effectses_ES
dc.subject.koFentanyles_ES
dc.subject.koadministration & dosagees_ES
dc.subject.koFentanyles_ES
dc.subject.kopharmacologyes_ES
dc.subject.koLocus Coeruleuses_ES
dc.subject.kodrug effectses_ES
dc.subject.koLocus Coeruleuses_ES
dc.subject.kometabolismes_ES
dc.subject.koMalees_ES
dc.subject.koMorphinees_ES
dc.subject.koadministration & dosagees_ES
dc.subject.koMorphinees_ES
dc.subject.kopharmacologyes_ES
dc.subject.koNociceptiones_ES
dc.subject.kodrug effectses_ES
dc.subject.koPeriaqueductal Grayes_ES
dc.subject.kodrug effectses_ES
dc.subject.koPeriaqueductal Grayes_ES
dc.subject.kometabolismes_ES
dc.subject.koRatses_ES
dc.subject.koRats, Wistares_ES
dc.subject.koReceptors, Opioid, mues_ES
dc.subject.koagonistses_ES
dc.subject.koReceptors, Opioid, mues_ES
dc.subject.kometabolismes_ES
dc.subject.koAnalgesics, Opioides_ES
dc.subject.koArrestinses_ES
dc.subject.koReceptors, Opioid, mues_ES
dc.subject.kobeta-arrestines_ES
dc.subject.koFentanyles_ES
dc.subject.koMorphinees_ES


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