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dc.contributor.authorRivera-Ramirez, Alicia 
dc.contributor.authorValderrama-Carvajal, Alejandra
dc.contributor.authorRoales-Buján, Ruth
dc.contributor.authorSuárez-Boomgaard, Diana
dc.contributor.authorMedina-Luque, José
dc.contributor.authorShumilov, Kirill
dc.contributor.authorDe-la-Calle-Martin, Adelaida 
dc.date.accessioned2015-10-05T09:06:35Z
dc.date.available2015-10-05T09:06:35Z
dc.date.created2015
dc.date.issued2015-10-05
dc.identifier.urihttp://hdl.handle.net/10630/10428
dc.description.abstractMorphine is one of the most potent analgesic drugs used to relieve moderate to severe pain. After long-term use of morphine, neuroadaptive changes in the brain promotes tolerance, which result in a reduced sensitivity to most of its effects with attenuation of analgesic efficacy, and dependence, revealed by drug craving and physical or psychological manifestations of drug withdrawal. The mu opioid receptor (MOR) is critical, not only in mediating morphine analgesia, but also in addictive behaviors by the induction of a strong rewarding effect. We have previously shown that dopamine D4 receptor (D4R) stimulation counteracts morphine-induced activation of dopaminergic nigrostriatal pathway and accumulation of Fos family transcription factors in the caudate putamen (CPu). In the present work, we have studied the effect of D4R activation on MOR changes induced by morphine in the rat CPu on a continuous drug treatment paradigm, by analyzing MOR protein level, pharmacological profile, and functional coupling to G proteins. Furthermore, using conditioned place preference and withdrawal syndrome test, we have investigated the role of D4R activation on morphine-related behavioural effects. MOR immunoreactivity, agonist binding density and its coupling to G proteins are up-regulated in the striosomes by continuous morphine treatment. Interestingly, co-treatment of morphine with the dopamine D4 receptor (D4R) agonist PD168,077 fully counteracts these adaptive changes in MOR, in spite of the fact that continuous PD168,077 treatment increases the [3H]DAMGO Bmax values to the same degree as seen after continuous morphine treatment. In addition, the administration of the D4R agonist counteracts the rewarding effects of morphine, as well as the development of physical dependence. The present results give support for the existence of antagonistic functional D4R-MOR receptor-receptor interactions in the adaptive changes occurring in MOR of striosomes on continuous administration of morphine and preventing morphine-related behaviour.es_ES
dc.description.sponsorshipUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Teches_ES
dc.language.isoenges_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectEndorfinas - Receptoreses_ES
dc.subjectMorfinaes_ES
dc.subject.otherAdicciónes_ES
dc.subject.otherReceptor D4es_ES
dc.titleDopamine D4 receptor counteracts morphine-induced changes in M opioid receptor signaling in the striosomes of the rat caudate putamen.es_ES
dc.typeinfo:eu-repo/semantics/conferenceObjectes_ES
dc.centroFacultad de Cienciases_ES
dc.relation.eventtitle16 National Congress of the Spanish Society of Neurosciencees_ES
dc.relation.eventplaceGranadaes_ES
dc.relation.eventdate23-25 Septiembre 2015es_ES
dc.identifier.orcidhttp://orcid.org/0000-0002-7282-0441es_ES
dc.cclicenseby-nc-ndes_ES


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