RGD Reference Report - CP-154,526 Modifies CREB Phosphorylation and Thioredoxin-1 Expression in the Dentate Gyrus following Morphine-Induced Conditioned Place Preference. - Rat Genome Database

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CP-154,526 Modifies CREB Phosphorylation and Thioredoxin-1 Expression in the Dentate Gyrus following Morphine-Induced Conditioned Place Preference.

Authors: García-Carmona, Juan-Antonio  Camejo, Daymi M  Almela, Pilar  Jiménez, Ana  Milanés, María-Victoria  Sevilla, Francisca  Laorden, María-Luisa 
Citation: García-Carmona JA, etal., PLoS One. 2015 Aug 27;10(8):e0136164. doi: 10.1371/journal.pone.0136164. eCollection 2015.
RGD ID: 401940184
Pubmed: PMID:26313266   (View Abstract at PubMed)
PMCID: PMC4551807   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0136164   (Journal Full-text)

Corticotropin-releasing factor (CRF) acts as neuro-regulator of the behavioral and emotional integration of environmental and endogenous stimuli associated with drug dependence. Thioredoxin-1 (Trx-1) is a functional protein controlling the redox status of several proteins, which is involved in addictive processes. In the present study, we have evaluated the role of CRF1 receptor (CRF1R) in the rewarding properties of morphine by using the conditioned place preference (CPP) paradigm. We also investigate the effects of the CRF1R antagonist, CP-154,526, on the morphine CPP-induced activation of CRF neurons, CREB phosphorylation and Trx expression in paraventricular nucleus (PVN) and dentate gyrus (DG) of the mice brain. CP-154,526 abolished the acquisition of morphine CPP and the increase of CRF/pCREB positive neurons in PVN. Moreover, this CRF1R antagonist prevented morphine-induced CRF-immunoreactive fibers in DG, as well as the increase in pCREB expression in both the PVN and DG. In addition, morphine exposure induced an increase in Trx-1 expression in DG without any alterations in PVN. We also observed that the majority of pCREB positive neurons in DG co-expressed Trx-1, suggesting that Trx-1 could activate CREB in the DG, a brain region involved in memory consolidation. Altogether, these results support the idea that CRF1R antagonist blocked Trx-1 expression and pCREB/Trx-1 co-localization, indicating a critical role of CRF, through CRF1R, in molecular changes involved in morphine associated behaviors.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
morphine dependence treatmentISOCreb1 (Mus musculus)401940184; 401940184 RGD 
morphine dependence treatmentIDA 401940184 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Creb1  (cAMP responsive element binding protein 1)

Genes (Mus musculus)
Creb1  (cAMP responsive element binding protein 1)

Genes (Homo sapiens)
CREB1  (cAMP responsive element binding protein 1)


Additional Information