Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice

Abstract

Background: Hallucinogenic drugs were used to treat alcoholic patients in the past, and recent developments in the study of hallucinogens led to a renewal of interest regarding the application of these drugs in the treatment of addiction. in this scenario, accumulating evidence suggests that the hallucinogenic brew ayahuasca (Aya) may have therapeutic effects on substance abuse problems.Methods: We investigated the effects of Aya on spontaneous locomotor activity and ethanol(Eth)-induced hyperlocomotion and subsequent locomotor sensitization by a two-injection protocol. Additionally, we tested the effect of Aya on an 8-day counter-sensitization protocol to modify sensitized responses induced by a repeated treatment with Eth (1.8 g/kg) for 8 alternate days.Results: Aya showed high sensitivity in preventing the development of Eth-induced behavioral sensitization, attenuating it at all doses (30, 100, 200, 300 or 500 mg/kg) without modifying spontaneous locomotor activity. At the highest doses (300 and 500 mg/kg), Aya also showed selectivity to both acute and sensitized Eth responses. Finally, a counter-sensitization strategy with 100 or 300 mg/kg of Aya for 8 consecutive days after the establishment of Eth-induced behavioral sensitization was effective in blocking its subsequent expression on an Eth challenge.Conclusions: We demonstrated that Aya not only inhibits early behaviors associated with the initiation and development of Eth addiction, but also showed effectiveness in reversing long-term drug effects expression, inhibiting the reinstatement of Eth-induced behavioral sensitization when administered in the Eth-associated environment. (C) 2015 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundo de Auxilio aos Docentes e Alunos (FADA/UNIFESP)Associacao Fundo de Incentivo Pesquisa (AFIP)Univ Estadual Santa Cruz, Dept Hlth Sci, BR-456620 Ilheus, BA, BrazilUniv Estadual Santa Cruz, Dept Biol Sci, BR-456620 Ilheus, BA, BrazilUniversidade Federal de São Paulo, Dept Physiol, BR-04023062 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, BR-04023062 São Paulo, SP, BrazilUniv Braz Cubes, Hlth Div, BR-1233 Mogi Dos Cruzes, SP, BrazilCriminalist Inst São Paulo, Forens Toxicol & Chem Lab, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Physiol, BR-04023062 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, BR-04023062 São Paulo, SP, BrazilWeb of Scienc