Regulation of cocaine reward by CREB.
Science
; 282(5397): 2272-5, 1998 Dec 18.
Article
en En
| MEDLINE
| ID: mdl-9856954
ABSTRACT
Cocaine regulates the transcription factor CREB (adenosine 3', 5'-monophosphate response element binding protein) in rat nucleus accumbens, a brain region that is important for addiction. Overexpression of CREB in this region decreases the rewarding effects of cocaine and makes low doses of the drug aversive. Conversely, overexpression of a dominant-negative mutant CREB increases the rewarding effects of cocaine. Altered transcription of dynorphin likely contributes to these effects Its expression is increased by overexpression of CREB and decreased by overexpression of mutant CREB. Moreover, blockade of kappa opioid receptors (on which dynorphin acts) antagonizes the negative effect of CREB on cocaine reward. These results identify an intracellular cascade-culminating in gene expression-through which exposure to cocaine modifies subsequent responsiveness to the drug.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Recompensa
/
Cocaína
/
Proteína de Unión a Elemento de Respuesta al AMP Cíclico
/
Núcleo Accumbens
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Science
Año:
1998
Tipo del documento:
Article
País de afiliación:
Estados Unidos