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Different contribution of glucocorticoids in the basolateral amygdala to the formation and expression of opiate withdrawal-associated memories

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dc.contributor.authorFerenczi, Szilamer
dc.contributor.authorKovács, Krisztina J.
dc.contributor.authorNúñez Parra, Cristina
dc.contributor.authorGarcía Pérez, Daniel
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.accessioned2026-02-12T09:12:11Z
dc.date.available2026-02-12T09:12:11Z
dc.date.copyright© 2016 Elsevier Ltd.
dc.date.issued2016-10-08
dc.description.abstractDrug-withdrawal aversive memories generate a motivational state leading to compulsive drug taking, with plasticity changes in the basolateral amygdala (BLA) being essential in aversive motivational learning. The conditioned-place aversion (CPA) paradigm allows for measuring the negative affective component of drug withdrawal. First, CPA triggers association between negative affective consequences of withdrawal with context (memory consolidation). Afterwards, when the animals are re-exposed to the paired environment, they avoid it due to the association between the context and aversive memories (memory retrieval). We examined the influence of glucocorticoids (GCs) for a morphine-withdrawal CPA paradigm, along with plasticity changes in the BLA, in sham-operated and adrenalectomized (ADX) animals. We demonstrated that sham + morphine animals robustly displayed CPA, whereas ADX-dependent animals lacked the affective-like signs of opiate withdrawal but displayed increased somatic signs of withdrawal. Glucocorticoid receptor (GR) actions promote memory consolidation but highly depend on increases in GC levels. Interestingly, we observed that GCs were only increased in sham-dependent rodents during aversive-withdrawal memory consolidation, and that GR expression correlated with phosphorylated cAMP response element binding (pCREB) protein, early growth response 1 (Egr-1) and activity-regulated cytoskeletal-associated (Arc) mRNA induction in this experimental group. In contrast, ADX-animals displayed reduced (pCREB). GCs are also known to impair memory retrieval. Accordingly, we showed that GCs levels remained at basal levels in all experimental groups following memory retrieval, and consequently GRs no longer acted as transcriptional regulators. Importantly, memory retrieval elicited increased pCREB levels in sham + morphine animals (not in ADX + morphine group), which were directly correlated with enhanced Arc mRNA/protein expression mainly in glutamatergic neurons. In conclusion, context-withdrawal associations are accompanied plasticity changes in the BLA, which are, in part, regulated by GR signaling. Moreover, dysregulation of CREB signaling, in part through Arc expression, may enhance reconsolidation, resulting in the maintenance of excessive aversive states. These findings might have important implications for drug-seeking behavior.
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dc.format.extent58
dc.identifier.citationPsychoneuroendocrinology, 2016, Vol. 74, pp. 350-362
dc.identifier.doihttps://doi.org/10.1016/j.psyneuen.2016.09.020
dc.identifier.eissn1873-3360
dc.identifier.issn0306-4530
dc.identifier.urihttp://hdl.handle.net/10201/204181
dc.languageeng
dc.publisherElsevier
dc.relationThis work was supported by grants from Ministerio de Ciencia e Innovación (SAF/FEDER 2009-07178; SAF/FEDER 2010-17907; 2013-49076-P), Spain; Red de Trastornos Adictivos, Spain; Fundación Séneca (15405/PI/10) and Instituto Murciano de Investigación en Biomedicina (IMIB), Región de Murcia, Spain. In Hungary, the work was supported by the National Research, Development and Innovation Fund109622 to K.J.K. and 109744 to S.F. Daniel García-Pérez was supported by a fellowship from Ministerio de Ciencia e Innovación (AP2009-2379).
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0306453016302104
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectMemory consolidation and retrieval
dc.subjectAdrenalectomy
dc.subjectmiRNAs
dc.subjectConditioned place aversion
dc.subjectMorphine dependence
dc.subjectTranscription factors
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleDifferent contribution of glucocorticoids in the basolateral amygdala to the formation and expression of opiate withdrawal-associated memories
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dspace.entity.typePublicationes
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relation.isAuthorOfPublication.latestForDiscovery353c85df-d611-4999-b8b7-960dd35d1011
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