Ayahuasca prevents the reinstatement of cocaine-induced rewarding effects in C57Bl/6 mice.

Abstract

<h4>Rationale</h4>Ayahuasca is a brew containing the psychedelic compound N,N-dimethyltryptamine (DMT) and β-carbolines, traditionally consumed in indigenous rituals. Recent studies suggest its potential to reduce depression and anxiety and as an alternative for treating ethanol and tobacco use disorders. However, research on its impact on cocaine use disorder remains limited.<h4>Objective</h4>To analyze the rewarding effects of ayahuasca and to evaluate its therapeutic application on the reinstatement of cocaine-induced conditioned place preference (CPP) in C57Bl/6 mice.<h4>Methods</h4>First, we examined if ayahuasca (2.5, 7.5, 12.5 and 15 mg DMT/kg, gavage) could induce CPP. Next, using a choice-based CPP paradigm, we compared the rewarding effects of cocaine (10 mg/kg, i.p.) with a previously established rewarding dose of ayahuasca (15 mg DMT/kg). Finally, we employed a cocaine-induced reinstatement protocol to assess whether ayahuasca could prevent the reactivation of cocaine-associated contextual preference. Therefore, mice were conditioned with cocaine and subsequently treated with water or ayahuasca (12.5 or 15 mg DMT/kg). Following a cocaine challenge, reinstatement of cocaine-induced CPP was evaluated.<h4>Results</h4>Our findings showed that while ayahuasca induced rewarding effects with the higher dose tested, these were less pronounced than those of cocaine. Moreover, ayahuasca treatment effectively prevented the cocaine-induced CPP reinstatement.<h4>Conclusion</h4>These findings support the therapeutic potential of ayahuasca in the context of cocaine use disorder.

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