Orexin A-mediated AKT signaling in the dentate gyrus contributes to the acquisition, expression and reinstatement of morphine-induced conditioned place preference.
Addict Biol
; 21(3): 547-59, 2016 May.
Article
en En
| MEDLINE
| ID: mdl-25757577
ABSTRACT
Accumulating evidence indicates that the hippocampal dentate gyrus (DG), a critical brain region contributing to learning and memory, is involved in the addiction and relapse to abused drugs. Emerging studies also suggest the role of orexin signaling in the rewarding behavior induced by repeated exposure to opiates. In the present study, we investigated the dynamic adaptation of orexin signaling in the DG and its functional significance in the acquisition, expression, maintenance of and relapse to rewarding behavior induced by morphine. Repeated place conditioning with morphine significantly increased the orexin A content released from the lateral hypothalamic area projecting neurons into the DG. Local infusions of orexin A into the DG sensitized the acquisition of and relapse to the conditioned place preference induced by morphine. The application of the orexin receptor type 1 (OXR1) antagonist SB334867 significantly abolished the acquisition, expression and maintenance of the conditioned place preference induced by repeated exposure to morphine. Furthermore, the significant increase of the phosphorylation of AKT in the DG was associated with preference for the morphine-paired chamber in rats, which was reversed by the local administration of an OXR1 antagonist. Thus, these findings suggested that the dynamic upregulation of orexin A signaling, via the AKT pathway in the DG, may promote the acquisition and maintenance of opioid-induced craving behaviors and may increase sensitivity to the rewarding effect of subsequent opioids.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Conducta de Elección
/
Condicionamiento Psicológico
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Giro Dentado
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Proteínas Proto-Oncogénicas c-akt
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Orexinas
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Analgésicos Opioides
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Morfina
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Trastornos Relacionados con Opioides
Tipo de estudio:
Prognostic_studies
Aspecto:
Patient_preference
Límite:
Animals
Idioma:
En
Revista:
Addict Biol
Asunto de la revista:
TRANSTORNOS RELACIONADOS COM SUBSTANCIAS
Año:
2016
Tipo del documento:
Article
País de afiliación:
China