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La serotonina activa un circuito de ansiedad y miedo en la amígdala extendida
Catherine A Marcinkiewcz1, Christopher M Mazzone1,2, Giuseppe D'Agostino3
1Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Nature
|August 25, 2016
Resumen
La serotonina del núcleo dorsal del rafe (5-HT DRN) activa un circuito de miedo y ansiedad en ratones. Esta vía explica los efectos adversos tempranos de los inhibidores selectivos de la recaptación de serotonina (ISRS).
Área de la Ciencia:
- La neurociencia
- Neurobiología
- Ciencias del comportamiento
Sus antecedentes:
- La serotonina (5-hidroxitriptamina, 5-HT) es crucial para la regulación emocional.
- Los circuitos neuronales específicos subyacentes a los estados aversivos mediados por 5-HT siguen sin estar claros.
Objetivo del estudio:
- Para aclarar los circuitos neuronales a través de los cuales la serotonina del núcleo dorsal del rafe (5-HT DRN) influye en el miedo y la ansiedad.
- Investigar el papel de este circuito en los primeros efectos adversos de los inhibidores selectivos de la recaptación de serotonina (ISRS).
Principales métodos:
- Se utilizaron modelos de ratón para investigar el papel de las proyecciones de 5-HT DRN en el núcleo del lecho de la estria terminal (BNST).
- Se examinó la participación de los receptores 5-HT2C (5-HT2CRs) y las neuronas del factor de liberación de corticotropina (CRF) en el BNST.
- Se evaluó el impacto del antagonismo del receptor CRF tipo 1 (CRF1R) en los comportamientos inducidos por ISRS.
Principales resultados:
- 5-HT DRN activa las neuronas CRF en el BNST (CRFBNST) a través de 5-HT2CRs.
- Esta activación suprime las salidas ansiolíticas del BNST, promoviendo el miedo y la ansiedad.
- El antagonismo de CRF1R impidió el aprendizaje aversivo inducido por los ISRS, lo que indica su papel en los primeros efectos secundarios de los ISRS.
Conclusiones:
- Identificó un circuito clave de 5-HT DRN → CRFBNST que regula el miedo y la ansiedad.
- Este circuito proporciona una explicación mecanicista de los eventos adversos tempranos observados en algunos pacientes durante el tratamiento con ISRS para trastornos de ansiedad.
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