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La dopaminación de la histona H3 en el área tegmental ventral regula la búsqueda de cocaína
Ashley E Lepack1, Craig T Werner2, Andrew F Stewart1
1Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Science (New York, N.Y.)
|April 11, 2020
Resumen
La adicción a la cocaína altera la expresión génica del cerebro a través de la modificación de las histonas. La reducción de la dopaminación de la histona H3 glutamina 5 (H3Q5dop) en el área tegmental ventral (VTA) revirtió estos cambios y redujo la búsqueda de cocaína.
Área de la Ciencia:
- La neurociencia
- Biología molecular
- Investigación de las adicciones
Sus antecedentes:
- La adicción a la cocaína está relacionada con cambios en las vías de recompensa del cerebro, especialmente las neuronas de dopamina en el área tegmental ventral (VTA).
- Los mecanismos precisos por los cuales la cocaína altera la expresión génica en las neuronas de dopamina del cerebro medio, contribuyendo a la adicción, siguen siendo incompletamente entendidos.
Objetivo del estudio:
- Investigar el papel de las modificaciones histónicas en los cambios de transcripción inducidos por la cocaína en el cerebro medio.
- Para determinar si la histona H3 glutamina 5 dopaminación (H3Q5dop) está involucrada en la adicción a la cocaína y las conductas de recaída.
Principales métodos:
- Utilizó un modelo de ratas de abstinencia de cocaína.
- Se midieron los niveles de dopaminación de la histona H3 glutamina 5 (H3Q5dop) en el VTA.
- Intervenciones administradas para reducir el H3Q5dop en el VTA durante la retirada.
- Cambios de expresión génica analizados, liberación de dopamina en el núcleo accumbens y comportamiento de búsqueda de cocaína.
Principales resultados:
- La abstinencia de la cocaína condujo a un aumento de la acumulación de H3Q5dop en el VTA.
- La reducción de H3Q5dop en el VTA revirtió las alteraciones de la expresión génica asociadas a la cocaína.
- La intervención también atenuó la liberación de dopamina en el núcleo accumbens y disminuyó el comportamiento de búsqueda de cocaína.
Conclusiones:
- La dopaminación de la histona H3 glutamina 5 (H3Q5dop) es crucial para la plasticidad transcripcional inducida por la cocaína en la ATV.
- La dopamina nuclear, independiente de la neurotransmisión, juega un papel importante en la expresión génica relacionada con la adicción y los comportamientos de recaída.
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