5-HT2A Receptor Knockout Mice Show Sex-Dependent Differences following Acute Noribogaine Administration.
International journal of molecular sciences January 5, 2024 Sofía Villalba, Bruno González, Stephanie Junge et al. 9 citations
Noribogaine, the primary metabolite of ibogaine, produces sexually dimorphic effects in mice, with some responses depending on the 5-HT2A receptor. A single 40 mg/kg dose reduced locomotion in male but not female wild-type mice. Gene expression of immediate early genes and glutamate receptors differed by sex and genotype. 5-HT2A receptor mRNA increased in the medial prefrontal cortex after noribogaine at 10 mg/kg in males and 40 mg/kg in females. Electrophysiology showed that 40 mg/kg reduced NMDA-mediated postsynaptic current density in layer V pyramidal neurons of the medial prefrontal cortex only in male wild-type mice, an effect absent in 5-HT2A receptor knockout males and all females. The genetic removal of the 5-HT2A receptor blunted noribogaine's effects on NMDA synaptic transmission.