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Mecanismo sináptico subyacente a la modulación de la serotonina de la transición a la adicción a la cocaína
Yue Li1,2, Linda D Simmler1,2, Ruud Van Zessen1,2
1Department of Basic Neurosciences, Medical Faculty, University of Geneva, CH-1211 Geneva, Switzerland.
Science (New York, N.Y.)
|September 13, 2021
Resumen
La serotonina (5-HT) juega un papel crucial en la adicción. Este estudio revela que la serotonina, no sólo la dopamina, impulsa las conductas compulsivas de búsqueda de drogas, impactando las estrategias de tratamiento de la adicción.
Área de la Ciencia:
- La neurociencia
- Farmacología
- Investigación de las adicciones
Sus antecedentes:
- La adicción se caracteriza por el uso compulsivo de drogas a pesar de los resultados negativos.
- Se sabe que la señalización de la dopamina mesolímbica conduce a comportamientos compulsivos.
- Los psicoestimulantes como la cocaína también aumentan la serotonina extracelular (5-HT) inhibiendo su recaptación.
Objetivo del estudio:
- Investigar el papel de la serotonina (5-HT) en la transición al consumo compulsivo de drogas.
- Para aclarar los mecanismos por los cuales la serotonina influye en los comportamientos relacionados con la adicción.
Principales métodos:
- Se utilizó el SERT Met172 knockin (SertKI) en ratones con un transportador de serotonina insensible a la cocaína.
- Administración de cocaína a través de paradigmas de autoadministración en ratones SertKI y de tipo salvaje.
- Utilizó manipulaciones farmacológicas para alterar los niveles de serotonina y la estimulación optogenética de las vías de dopamina.
- Receptores de serotonina específicos para la proyección generados en ratones con knockout.
Principales resultados:
- Los ratones SertKI mostraron una transición acelerada a la autoadministración compulsiva de cocaína, lo que indica el papel de la 5-HT.
- La elevación farmacológica de 5-HT revirtió el comportamiento compulsivo durante la estimulación impulsada por la dopamina.
- La serotonina induce la depresión presináptica en las sinapsis del estriado orbitofrontal a través de los receptores 5-HT1B.
- El nocaut de los receptores 5-HT1B en proyecciones específicas aumentó la incidencia de la autoadministración compulsiva de cocaína.
Conclusiones:
- La señalización de la serotonina, particularmente a través de los receptores 5-HT1B, modula significativamente la transición al uso compulsivo de drogas.
- La acción de la serotonina en las sinapsis corticostriatales específicas es un mecanismo clave subyacente a la adicción.
- Estos hallazgos destacan la serotonina como un objetivo crítico para las nuevas terapias de adicción.
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