Henriques Gabrielle M, Anjos-Santos Alexia, Rodrigues Isa R S, Nascimento-Rocha Victor, Reis Henrique S, Libarino-Santos Matheus, Barros-Santos Thaísa, Yokoyama Thais S, Bertagna Natalia B, Favoretto Cristiane A, Moraes Célia R G, Cruz Fábio C, Barbosa Paulo C R, Marinho Eduardo A V, Oliveira-Lima Alexandre J, Berro Laís F
Department of Health Sciences, Universidade Estadual De Santa Cruz, Ilhéus, Brazil.
Department of Pharmacology, Universidade Federal De São Paulo, São Paulo, Brazil.
Front Pharmacol. 2021 Sep 21;12:739012. doi: 10.3389/fphar.2021.739012. eCollection 2021.
Ibogaine is a psychedelic extracted from the plant , natural from Africa, and has been proposed as a potential treatment for substance use disorders. In animal models, ibogaine reduces ethanol self-administration. However, no study to date has investigated the effects of ibogaine on ethanol-induced conditioned place preference (CPP). The present study aimed to investigate the effects of repeated treatment with ibogaine on the reinstatement of CPP to ethanol in male mice. The rewarding effects of ethanol (1.8 g/kg, i. p.) or ibogaine (10 or 30 mg/kg, p. o.) were investigated using the CPP model. Furthermore, we evaluated the effects of repeated treatment with ibogaine (10 or 30 mg/kg, p. o.) on the reinstatement of ethanol-induced CPP. Reinstatement was evaluated under two conditions: 1) during a priming injection re-exposure test in which animals received a priming injection of ethanol and had free access to the CPP apparatus; 2) during a drug-free test conducted 24 h after a context-paired re-exposure, in which subjects received an injection of ethanol and were confined to the compartment previously conditioned to ethanol. Our results show that ethanol, but not ibogaine, induced CPP in mice. Treatment with ibogaine after conditioning with ethanol blocked the reinstatement of ethanol-induced CPP, both during a drug priming reinstatement test and during a drug-free test conducted after re-exposure to ethanol in the ethanol-paired compartment. Our findings add to the literature suggesting that psychedelics, in particular ibogaine, may have therapeutic properties for the treatment of alcohol use disorder at doses that do not have rewarding effects .
伊博格碱是一种从植物中提取的迷幻剂,原产于非洲,已被提议作为治疗物质使用障碍的一种潜在药物。在动物模型中,伊博格碱可减少乙醇的自我给药。然而,迄今为止尚无研究调查伊博格碱对乙醇诱导的条件性位置偏爱(CPP)的影响。本研究旨在探讨重复给予伊博格碱对雄性小鼠乙醇诱导的CPP恢复的影响。使用CPP模型研究了乙醇(1.8 g/kg,腹腔注射)或伊博格碱(10或30 mg/kg,口服)的奖赏效应。此外,我们评估了重复给予伊博格碱(10或30 mg/kg,口服)对乙醇诱导的CPP恢复的影响。在两种条件下评估恢复情况:1)在一次启动注射再暴露试验中,动物接受乙醇启动注射并可自由进入CPP装置;2)在与环境配对的再暴露后24小时进行的无药试验中,受试动物接受乙醇注射并被限制在先前与乙醇配对的隔室内。我们的结果表明,乙醇而非伊博格碱可在小鼠中诱导CPP。在用乙醇进行条件化后给予伊博格碱治疗,在药物启动恢复试验期间以及在与乙醇配对的隔室内再次暴露于乙醇后进行的无药试验期间,均阻断了乙醇诱导的CPP的恢复。我们的研究结果进一步表明,迷幻剂,尤其是伊博格碱,在不产生奖赏效应的剂量下可能具有治疗酒精使用障碍的特性。