Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, CONICET-Universidad Austral, Mariano Acosta 1611, Buenos Aires B1629WWA, Argentina.
2 papers in the library · 10 citations · publishing 2024-2025
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.
Noribogaine, the primary metabolite of the atypical psychedelic ibogaine, alters thalamic calcium channel gene expression and current density in mice in a sex- and 5-HT2A receptor-dependent manner. A single injection of 10 mg/kg noribogaine increased CACNA1g (T-type) mRNA expression only in wild-type males and knockout females, indicating receptor- and sex-specific effects. The same dose increased CACNA1a (P/Q-type) expression in both sexes and decreased HCN2 expression in females of both genotypes but only in knockout males. Bath-applied noribogaine (50 μM) blocked T-type calcium current density only in knockout females, not in wild-type females or males. Baseline calcium current density was also higher in female ventrobasal neurons, further suggesting sex-dependent differences.