5-HT2A Receptor Knockout Mice Show Sex-Dependent Differences following Acute Noribogaine Administration
Dublin Core
Título
5-HT2A Receptor Knockout Mice Show Sex-Dependent Differences following Acute Noribogaine Administration
Tema
PSICODELICOS
NORIBOGAINA
SEROTONINA
RECEPTORES DE GLUTAMATO
GENES DE EXPRESION INMEDIATA TEMPRANA
IEG
BIBLIOGRAFIA NACIONAL QUIMICA
2024
Abstract
Noribogaine (noribo) is the primary metabolite from ibogaine, an atypical psychedelic alkaloid isolated from the root bark of the African shrub Tabernanthe iboga. The main objective of this study was to test the hypothesis that molecular, electrophysiological, and behavioral responses of noribo are mediated by the 5-HT2A receptor (5-HT2AR) in mice. In that regard, we used male and female, 5-HT2AR knockout (KO) and wild type (WT) mice injected with a single noribo dose (10 or 40 mg/kg; i.p.). After 30 min., locomotor activity was recorded followed by mRNA measurements by qPCR (immediate early genes; IEG, glutamate receptors, and 5-HT2AR levels) and electrophysiology recordings of layer V pyramidal neurons from the medial prefrontal cortex. Noribo 40 decreased locomotion in male, but not female WT. Sex and genotype differences were observed for IEG and glutamate receptor expression. Expression of 5-HT2AR mRNA increased in the mPFC of WT mice following Noribo 10 (males) or Noribo 40 (females). Patch-clamp recordings showed that Noribo 40 reduced the NMDA-mediated postsynaptic current density in mPFC pyramidal neurons only in male WT mice, but no effects were found for either KO males or females. Our results highlight that noribo produces sexually dimorphic effects while the genetic removal of 5HT2AR blunted noribo-mediated responses to NMDA synaptic transmission.
Autor
Villalba, Sofía
González, Bruno
Junge, Stephanie
Bernardi, Alejandra
González Arbildi, Joaquín
Fagúndez, Catherine
Torterolo Minetti, Pablo Daniel
Carrera, Ignacio
Urbano, Francisco J.
Bisagno, Verónica
Fuente
International Journal of Molecular Sciences, v.25. n°2, 2024. --
Editor
MDPI
Fecha
2024
Formato
PDF
Extent
18 p.
Idioma
Inglés
Tipo
Artículo
Identificador
10.3390/ijms25020687
Document Item Type Metadata
Original Format
PDF
- Fecha de agregación
- May 15, 2024
- Colección
- Bibliografía Nacional Química
- Tipo de Elemento
- Document
- Etiquetas
- Genes de expresion inmediata temprana, IEG, Noribogaina, Psicodélicos, Receptores de glutamato, Serotonina
- Citación
- Villalba, Sofía, “5-HT2A Receptor Knockout Mice Show Sex-Dependent Differences following Acute Noribogaine Administration,” RIQUIM - Repositorio Institucional de la Facultad de Química - UdelaR, accessed July 3, 2024, https://riquim.fq.edu.uy/items/show/6786.
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