RGD Reference Report - Glucocorticoid Homeostasis in the Dentate Gyrus Is Essential for Opiate Withdrawal-Associated Memories. - Rat Genome Database

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Glucocorticoid Homeostasis in the Dentate Gyrus Is Essential for Opiate Withdrawal-Associated Memories.

Authors: García-Pérez, Daniel  Ferenczi, Szilamer  Kovács, Krisztina J  Laorden, M Luisa  Milanés, M Victoria  Núñez, Cristina 
Citation: García-Pérez D, etal., Mol Neurobiol. 2017 Oct;54(8):6523-6541. doi: 10.1007/s12035-016-0186-7. Epub 2016 Oct 11.
RGD ID: 401959609
Pubmed: PMID:27730515   (View Abstract at PubMed)
DOI: DOI:10.1007/s12035-016-0186-7   (Journal Full-text)

Drug-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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ARCHumanwithdrawal disorder  ISOArc (Mus musculus)associated with morphine dependence more ...RGD 
ArcRatwithdrawal disorder  ISOArc (Mus musculus)associated with morphine dependence more ...RGD 
ArcMousewithdrawal disorder  IEP associated with morphine dependence more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Arc  (activity-regulated cytoskeleton-associated protein)

Genes (Mus musculus)
Arc  (activity regulated cytoskeletal-associated protein)

Genes (Homo sapiens)
ARC  (activity regulated cytoskeleton associated protein)


Additional Information