Effects of Ayahuasca on Ethanol-Conditioned Place Preference and ΔFosB Expression in the Nucleus Accumbens in Mice

Abstract Background Ayahuasca, a psychoactive Amazonian preparation, is increasingly studied for substance-use disorders. Objectives Investigate whether oral lyophilised-ayahuasca attenuates ethanol-induced conditioned place preference (CPP) in mice and alters ΔFosB expression in nucleus accumbens (NAc). Methods Male Swiss mice received water or ayahuasca (130-1950 mg/kg, p.o.) 30 min before each of eight ethanol pairings (2g/kg i.p.) in a CPP paradigm. A separate cohort underwent acute toxicology (650–5000mg/kg) with behavioural-observation and rotarod. Alkaloids were quantified by LC-MS/MS. ΔFosB-immunoreactive nuclei were counted in NAc 24h after the CPP post-test. Results Alkaloids levels were within traditional ranges. High-dose ayahuasca(5000 mg/kg) produced transient-serotonergic-syndrome-like signs and rotarod locomotor-deficit; lower doses did not express toxicity. Ethanol produced a moderate-CPP in controls(ΔTime≈+60s), whereas ayahuasca-pretreatment abolished preference at all doses(ΔTime within±7s). One-way ANOVA on ΔTime showed a robust-Treatment effect(F(3,36)=8.83, p=0.00016); Tukey tests: control differed from each ayahuasca group (all p<0.05), with no differences among ayahuasca doses. ΔFosB density did not differ among groups(p>0.05). Conclusions Ayahuasca was well tolerated at ceremonies-equivalent doses and blocked ethanol-induced-CPP across all doses, while ΔFosB levels in NAc were unchanged at 24h. Limitations on the CPP baseline and ΔFosB results may limit sensitivity, generalisability and interpretation. Findings provide preliminary evidence that ayahuasca-pretreatment may blunt ethanol-context preference, reinforcing the need of replication with stronger reward baselines, naïve controls and complementary molecular markers.