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Los psicodélicos promueven la neuroplasticidad a través de la activación de los receptores intracelulares 5-HT2A
Maxemiliano V Vargas1,2, Lee E Dunlap2,3, Chunyang Dong4
1Neuroscience Graduate Program, University of California, Davis, Davis, CA 95618, USA.
Science (New York, N.Y.)
|February 16, 2023
Resumen
Los psicodélicos promueven la plasticidad cerebral mediante la activación de los receptores intracelulares de 5-hidroxitriptamina (serotonina) 2A (5-HT2AR), a diferencia de la propia serotonina. Este descubrimiento destaca las AR5-HT2 intracelulares como un nuevo objetivo terapéutico para los trastornos neuropsiquiátricos.
Área de la Ciencia:
- La neurociencia
- Farmacología
- Biología molecular
Sus antecedentes:
- La disminución de la densidad de la columna dendrítica cortical es un sello distintivo de las enfermedades neuropsiquiátricas.
- Los efectos terapéuticos de los psicodélicos están relacionados con la promoción del crecimiento y la plasticidad de las neuronas corticales.
- La activación de los receptores de 5-hidroxitriptamina (serotonina) 2A (5-HT2AR) es crucial para esta plasticidad.
Objetivo del estudio:
- Investigar el mecanismo por el cual los psicodélicos promueven la neuroplasticidad.
- Para determinar por qué sólo ciertos agonistas de 5-HT2AR inducen la neuroplasticidad.
- Para aclarar el papel de la ubicación del receptor en la señalización 5-HT2AR.
Principales métodos:
- Utilizó herramientas moleculares y genéticas.
- Las vías de señalización intracelular 5-HT2AR investigadas.
- Comparó los efectos de los agonistas psicodélicos frente a la serotonina en los 5-HT2AR.
Principales resultados:
- Se demostró que las 5-HT2ARs intracelulares median los efectos promotores de la plasticidad de los psicodélicos.
- Se demostró que la serotonina no activa mecanismos de plasticidad similares, lo que explica sus diferentes efectos.
- Destacó la importancia del sesgo de la ubicación del receptor en la señalización de 5-HT2AR.
Conclusiones:
- Las 5-HT2ARs intracelulares son mediadores clave de la plasticidad cortical inducida por psicodélicos.
- Se identificaron 5-HT2ARs intracelulares como un objetivo terapéutico potencial para las afecciones neuropsiquiátricas.
- Sugiere que la serotonina puede no ser el ligando endógeno para los 5-HT2ARs intracelulares en la corteza.
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