Ayahuasca blocks the reinstatement of methylphenidate-induced conditioned place preference in mice: behavioral and brain
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ORIGINAL INVESTIGATION
Ayahuasca blocks the reinstatement of methylphenidate-induced conditioned place preference in mice: behavioral and brain Fos expression evaluations Henrique S. Reis 1 & Isa R. S. Rodrigues 1 & Alexia Anjos-Santos 1 & Matheus Libarino-Santos 1 & Yasmim A. Serra 1 & Elisângela G. Cata-Preta 1 & Daniella Oliveira-Campos 1 & Natali D. Kisaki 1 & Thaísa Barros-Santos 1 & Thais S. Yokoyama 2 & Fabio C. Cruz 2 & Alexandre J. Oliveira-Lima 1 & Paulo C. R. Barbosa 1 & Lais F. Berro 1,3 & Eduardo A. V. Marinho 1 Received: 4 February 2020 / Accepted: 9 July 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale Accumulating 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. Objectives The aim of the present study was to investigate the effects of treatment with ayahuasca on the rewarding properties of the psychostimulant methylphenidate. Methods The 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. Results Both 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. Conclusions Our 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. Keywords Ayahuasca . Conditioned place preference . Fos . Methylphenidate . Mice
Introduction * Lais F. Berro [email protected] * Eduardo A. V. Marinho [email protected] 1
Department of Health Sciences, Universidade Estadual de Santa Cruz, Rod. Ilhéus/Itabuna, Km 16, Ilhéus, BA 45662-0, Brazil
2
Department of Pharmacology, Universidade Federal de São Paulo, Leal Prado Building, Botucatu 862 Street, 04024-002, Vila Clementino, São Paulo, SP, Brazil
3
Department of Psychiatry and Human Behavior, Un
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