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Ayahuasca blocks the reinstatement of methylphenidate-induced conditioned place preference in mice: behavioral and brain Fos expression evaluations

Henrique Sousa Reis, Isa R. S. Rodrigues, Alexia Anjos-Santos, Matheus Libarino-Santos, Yasmim A. Serra, Elisangela Gouveia Cata-Preta, Daniella Oliveira-Campos, Natali D. Kisaki, Thaísa Barros-Santos, Thaís S. Yokoyama, Fábio Cardoso Cruz, Alexandre J. Oliveira-Lima, Paulo César Ribeiro Barbosa, Laís F. Berro, E.a.v. Marinho

Psychopharmacology July 16, 2020 DOI: 10.1007/s00213-020-05609-6 via OpenAlex

Summary

AI-generated from the abstract

Ayahuasca, a hallucinogenic beverage used in traditional Amazonian rituals, blocked the reinstatement of methylphenidate-induced conditioned place preference in mice, indicating reduced drug-seeking behavior. Both ayahuasca (100 mg/kg, orally) and methylphenidate (10 mg/kg, i.p.) separately induced conditioned place preference. However, methylphenidate altered Fos expression in several limbic brain regions associated with drug abuse, while ayahuasca had limited effects on Fos expression. Treatment with ayahuasca after conditioning with methylphenidate prevented reinstatement of the conditioned place preference and generally blocked the changes in Fos expression induced by methylphenidate conditioning or reexposure. These findings suggest ayahuasca restored normal brain function in areas linked to long-term drug wanting or seeking.

Study at a glance

Characteristics Experimental study Peer reviewed
Population Mice
Interventions Ayahuasca Methylphenidate
Dose 100 mg/kg ayahuasca orally; 10 mg/kg methylphenidate i.p.
Topics Ayahuasca
Keywords Methylphenidate Infralimbic cortex Ventral tegmental area Conditioned place preference
Citations 21
Key finding Ayahuasca treatment after conditioning with methylphenidate blocked the reinstatement of methylphenidate-induced conditioned place preference and generally reversed methylphenidate-induced changes in Fos expression in limbic brain regions.

Abstract

RationaleAccumulating evidence suggests that ayahuasca, a hallucinogenic beverage used in traditional Amazonian communities for ritualistic and curative purposes, has been associated with reduced rates of substance use disorders. However, the brain mechanisms underlying the therapeutic effects of ayahuasca have not yet been fully elucidated.ObjectivesThe aim of the present study was to investigate the effects of treatment with ayahuasca on the rewarding properties of the psychostimulant methylphenidate.MethodsThe rewarding properties of ayahuasca (100 mg/kg, orally) and methylphenidate (10 mg/kg, i.p.) were investigated using the conditioned place preference (CPP) model. Furthermore, we evaluated the effects of repeated treatment with ayahuasca on the reinstatement of methylphenidate-induced CPP. Fos expression was evaluated in different limbic structures (cingulate cortex-area 1, prelimbic cortex, infralimbic cortex, orbitofrontal cortex-lateral orbital area, nucleus accumbens core and shell, ventral tegmental area, dorsal striatum, and basolateral amygdala) upon each experimental phase.ResultsBoth ayahuasca and methylphenidate induced CPP in mice. However, ayahuasca had limited effects on Fos expression, while methylphenidate altered Fos expression in several brain regions associated with the behavioral effects of drugs of abuse. Treatment with ayahuasca after conditioning with methylphenidate blocked the reinstatement of methylphenidate-induced CPP. Those behavioral effects were accompanied by changes in Fos expression patterns, with ayahuasca generally blocking the changes in Fos expression induced by conditioning with methylphenidate and/or reexposure to methylphenidate.ConclusionsOur findings suggest that ayahuasca restored normal brain function in areas associated with the long-term expression of drug wanting/seeking in animals conditioned to methylphenidate.

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