Effects of Ayahuasca on Ethanol-Conditioned Place Preference and ΔFosB Expression in the Nucleus Accumbens in Mice
bioRxiv Preprint Server May 7, 2024 Victor Distefano Wiltenburg, Gabriela Morales-Lima, Aline Valéria Sousa Santos et al. preprint
Oral lyophilized ayahuasca, at doses equivalent to those used in traditional ceremonies, blocked the conditioned place preference (CPP) that mice normally develop for ethanol. In a CPP paradigm, mice pretreated with ayahuasca showed no preference for the ethanol-paired compartment (time difference within ±7 seconds), while controls showed a moderate preference (about +60 seconds). The effect was significant at all tested doses, and no differences were observed among ayahuasca groups. Ayahuasca was well tolerated at ceremony-equivalent doses, though the highest dose (5000 mg/kg) produced transient serotonergic-syndrome-like signs and locomotor deficits. ΔFosB expression in the nucleus accumbens did not differ among groups 24 hours after the post-test. The findings suggest ayahuasca may blunt ethanol-context preference, warranting replication with stronger reward baselines and additional molecular markers.