5-HT2A RECEPTOR DEFICIENCY ALTERS LOCOMOTION AND PREFRONTAL CORTEX GENE EXPRESSION INDUCED BY A SINGLE ADMINISTRATION OF THE ATYPICAL PSYCHEDELIC NORIBOGAINE IN MICE: GENDER DIFFERENCES

VILLALBA S; GONZALEZ B; JUNGE S; BERNARDI A; GONZALEZ J; TORTEROLO P; CARRERA I; URBANO FJ; BISAGNO V

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

Sociedades SAIC SAB AAFE AACYTAL

Ibogaine is the main indole alkaloid isolated from the root bark of the African shrub Tabernanthe iboga. It is an atypical psychedelic drug capable of inducing oneirogenic effects (waking dream-like states) and vivid memory recall. Although the subjective and behavioral effects they induce are quite dramatic, they possess little addictive potential when compared to other drugs. Ibogaine is metabolized mainly by CYP2D6 to the primary metabolite Noribogaine (Noribo). The main objective of this study was to analyze the contribution of 5-HT2A receptor (5HT2AR) on the molecular and behavioral responses of Noribo since it has been suggested that at least some of the effects of are linked to 5-HT2A activation. We used the 5-HT2A receptor knockout (KO) (5-HT2A -/-) or wild type (WT), male and female mice. Mice were injected with a single Noribo dose (10 and 40 mg/kg), and qPCR was performed on several immediate early genes (IEG), glutamate receptors and 5-HT2AR in the medial prefrontal cortex (mPFC). Noribo decreased locomotion 30 mins. After injection in KO mice for both sexes but only WT males showed decreased locomotion. For male mice, we found that Noribo increased IEG expression (Npas4, Egr1, cFos) for KO mice (p