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Glucocorticoid homeostasis in the dentate gyrus is essential for opiate withdrawal-associated memories

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dc.contributor.authorGarcía Pérez, Daniel
dc.contributor.authorFerenczi, Szilamer
dc.contributor.authorKovács, Krisztina J.
dc.contributor.authorNúñez Parra, Cristina
dc.contributor.authorLaorden Carrasco, María Luisa
dc.contributor.authorMilanés Maquilón, María Victoria
dc.contributor.departmentFarmacología
dc.contributor.otherFacultad de Medicina
dc.date.accessioned2026-02-12T12:25:22Z
dc.date.available2026-02-12T12:25:22Z
dc.date.copyright© 2016 los autores
dc.date.issued2016-10-11
dc.description.abstractDrug-withdrawal-associated aversive memories might trigger relapse to drug-seeking behavior. However, changes in structural and synaptic plasticity, as well as epigenetic mechanisms, which may be critical for long-term aversive memory, have yet to be elucidated. We used male Wistar rats and performed conditioned-place aversion (CPA) paradigm to uncover the role of glucocorticoids (GCs) on plasticity-related processes that occur within the dentate gyrus (DG) during opiate-withdrawal conditioning (memory formation-consolidation) and after reactivation by re-exposure to the conditioned environment (memory retrieval). Rats subjected to conditioned morphine-withdrawal robustly expressed CPA, while adrenalectomy impaired naloxone-induced CPA. Importantly, while activity-regulated cytoskeletal-associated protein (Arc) expression was induced in sham- and ADX-dependent animals during the conditioning phase, Arc and early growth response 1 (Egr-1) induction was restricted to sham-dependent rats following memory retrieval. Moreover, we found a correlation between Arc induction and CPA score, and Arc was selectively expressed in the granular zone of the DG in dopaminoceptive, glutamatergic and GABAergic neurons. We further found that brain-derived neurotrophic factor was regulated in the opposite way during the test phase. Our results also suggest a role for epigenetic regulation on the expression of glucocorticoid receptors and Arc following memory retrieval. Our data provide the first evidence that GC homeostasis is important for the expression of long-term morphine-withdrawal memories. Moreover, our results support the idea that targeting Arc and Egr-1 in the DG may provide important insights into the role of these signaling cascades in withdrawal-context memory re-consolidation. Together, disrupting these processes in the DG might lead to effective treatments in drug addiction thereby rapidly and persistently reducing invasive memories and subsequent drug seeking.
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dc.format.extent52
dc.identifier.citationMol Neurobiol 54, 6523–6541 (2017)
dc.identifier.doihttps://doi.org/10.1007/s12035-016-0186-7
dc.identifier.eissn1559-1182
dc.identifier.issn0893-7648
dc.identifier.urihttp://hdl.handle.net/10201/204481
dc.languageeng
dc.publisherSpringer
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; and 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 Fund 109622 to KJK and 109744 to SzF. Daniel García-Pérez was supported by a fellowship from Ministerio de Ciencia e Innovación (AP2009-2379).
dc.relation.publisherversionhttps://link.springer.com/article/10.1007/s12035-016-0186-7
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.subjectAdrenalectomy
dc.subjectConditioned-place aversion
dc.subjectMemory consolidation and retrieval
dc.subjectMiRNAs
dc.subjectMorphine dependence
dc.subjectTranscription factors
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleGlucocorticoid homeostasis in the dentate gyrus is essential for opiate withdrawal-associated memories
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/acceptedVersión
dspace.entity.typePublicationes
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