Publication:
Morphine administration modulates expression of Argonaute 2 and dopamine-related transcription factors involved in midbrain dopaminergic neurons function

dc.contributor.authorGarcía Pérez, Daniel
dc.contributor.authorSáez Belmonte, F.
dc.contributor.authorNúñez Parra, Cristina
dc.contributor.authorLaorden Carrasco, María Luisa
dc.contributor.authorMilanés Maquilón, María Victoria
dc.contributor.departmentFarmacología
dc.contributor.otherFacultades de la UMU::Facultad de Medicina
dc.date.accessioned2026-02-16T09:20:34Z
dc.date.available2026-02-16T09:20:34Z
dc.date.copyright© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society
dc.date.issued2012-12-05
dc.description.abstractBackground and Purpose Alterations in transcription factors that regulate the development and maintenance of dopamine (DA) neurons (such as Nurr1 and Pitx3) play an important role in the pathogenesis of addiction diseases. We have examined the effects of acute and chronic morphine and morphine withdrawal on TH expression and activity as well as expression of Nurr1, Pitx3 and Ago2 in the ventral tegmental area (VTA) and nucleus accumbens (NAc) of the rat. Experimental Approach Rats were injected acutely with morphine and decapitated 1 or 2 h later. Another set of rats were made dependent on morphine by implantation of two morphine pellets. Precipitated withdrawal was induced by injection of naloxone. Ago2, Pitx3, Nurr1, total TH (tTH), TH phosphorylated at Ser31 and at Ser40, and 3,4-Dihydroxyphenylacetic acid, and DA determination in the VTA and/or NAc were measured using immunoblotting, HPLC and immunofluorescence. Key Results Acute morphine produced a marked increase in TH activity and DA turnover in the NAc, concomitantly with increased Nurr1 and Pitx3 expression in the VTA. In contrast, precipitated morphine withdrawal decreased TH activation, TH expression and did not increase DA turnover in the NAc. These effects paralleled decreases in Ago2 expression, which was accompanied by increased Nurr1 and Pitx3, TH activity and normalized TH protein levels in the VTA. Conclusions and Implications The combined decrease in Ago2 and increases in Nurr1 and Pitx3 might represent some of the mechanisms that served to protect against accumbal TH regulation observed in morphine withdrawn rats, which may be critical for DA bioavailability to influence behaviour.
dc.formatapplication/pdf
dc.format.extent13
dc.identifier.citationBritish Journal of Pharmacology, 2013, Vol. 168, Issue 8, pp. 1889–1901
dc.identifier.doihttps://doi.org/10.1111/bph.12083
dc.identifier.eissn1476-5381
dc.identifier.issn0007-1188
dc.identifier.urihttp://hdl.handle.net/10201/205421
dc.languageeng
dc.publisherWiley : British Pharmacological Society
dc.relationThis work was supported by the following grants: Ministerio de Ciencia e Imnovación (SAF/FEDER2009-07178, SAF/ FEDER2010-17907), Spain; Red de Trastornos Adictivos (RD06/0001/1006 and RD06/0001/1001), Spain; Fundación Séneca, Agencia Regional de Ciencia y Tecnología Región de Murcia (15405/PI/10), Spain. D. G-P. was supported by a fellowship from the Ministerio de Ciencia e Imnovación (AP2009-2379).
dc.relation.publisherversionhttps://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.12083
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectTH
dc.subjectDA turnover
dc.subjectNurr1
dc.subjectPitx3
dc.subjectAgo2
dc.subjectOpiate dependence
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleMorphine administration modulates expression of Argonaute 2 and dopamine-related transcription factors involved in midbrain dopaminergic neurons function
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
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relation.isAuthorOfPublication.latestForDiscovery2f2500a1-1b27-4420-820c-db8c16e79afd
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