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Los efectos de la exposición crónica a la cocaína están regulados por la proteína neuronal Cdk55
1Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA. bibbj@rockvax.rockefeller.edu
Nature
|March 27, 2001
Resumen
La adicción a la cocaína implica adaptaciones cerebrales. Los investigadores descubrieron que DeltaFosB aumenta los niveles de cinasa 5 (Cdk5) dependiente de la ciclina, contribuyendo a estos cambios y potencialmente influyendo en la señalización del receptor de dopamina.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- Farmacología Farmacología.
Sus antecedentes:
- La adicción a la cocaína está relacionada con adaptaciones cerebrales que contrarrestan sus efectos.
- El uso crónico de cocaína altera la expresión génica a través de factores de transcripción como el DeltaFosB.
- DeltaFosB persiste en el estriado, lo que sugiere un papel en los cambios a largo plazo.
Objetivo del estudio:
- Para identificar objetivos aguas abajo de DeltaFosB en el estriado.
- Para investigar el papel de la cinasa 5 dependiente de ciclina (Cdk5) en la adicción a la cocaína.
Principales métodos:
- Utilizó análisis de matriz de ADN en ratones transgénicos inducibles.
- Se midieron los niveles de ARN, proteína y actividad del mensajero Cdk5.
- Inhibidores Cdk5 administrados para evaluar los efectos conductuales.
Principales resultados:
- La sobreexpresión de DeltaFosB y la cocaína crónica aumentaron los niveles de Cdk5 en el estriado.
- La actividad de Cdk5 fue elevada después de la exposición crónica a la cocaína.
- La inhibición de Cdk5 en el estriado potenciaba los efectos conductuales de la cocaína.
Conclusiones:
- La cinasa dependiente de ciclina 5 (Cdk5) es un objetivo aguas abajo de DeltaFosB.
- Los cambios mediados por DeltaFosB en Cdk5 contribuyen a los cambios adaptativos del cerebro en la adicción a la cocaína.
- Las alteraciones en la señalización de Cdk5, que involucran a los receptores de dopamina D1, están implicadas en la adicción a la cocaína.
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