Effect Of Ayahuasca on Experimental Models of Ethanol Addiction and Immunohistochemistry Analysis in Rodents

Abstract

BackgroundAyahuasca, a psychoactive Amazonian preparation, is increasingly studied for substance-use disorders. ObjectivesInvestigate whether oral lyophilised-ayahuasca attenuates ethanol-induced conditioned place preference (CPP) in mice and alters {Delta}FosB expression in nucleus accumbens (NAc). MethodsMale 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. {Delta}FosB-immunoreactive nuclei were counted in NAc 24h after the CPP post-test. ResultsAlkaloids 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({Delta}Time{approx}+60s), whereas ayahuasca-pretreatment abolished preference at all doses({Delta}Time within{+/-}7s). One-way ANOVA on {Delta}Time 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. {Delta}FosB density did not differ among groups(p>0.05). ConclusionsAyahuasca was well tolerated at ceremonies-equivalent doses and blocked ethanol-induced-CPP across all doses, while {Delta}FosB levels in NAc were unchanged at 24h. Limitations on the CPP baseline and {Delta}FosB 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, naive controls and complementary molecular markers.