Abstract
Ibogaine is a psychedelic extracted from the plant Tabernanthe iboga Baill. (Apocynaceae), 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 per se.
Highlights
Alcohol use disorder (AUD) is a global public health problem and a leading cause of absenteeism and death worldwide (SAMHSA, 2018; SAMHSA, 2019; Global Status Report on Alcohol and Health, 2018)
Conditioned Place Preference Score Two-way repeated measures (RM) analysis of variance (ANOVA) showed a significant interaction between treatment and time for conditioned place preference (CPP) score [F (3,28) 6.564; p 0.0017] (Figure 2)
Bonferroni post-hoc test showed that animals conditioned with ethanol showed a significant increase in CPP score compared to the same group during the pre-conditioning test (p 0.0061) and to the SAL group in the post-conditioning test (p 0.0009)
Summary
Alcohol (ethanol) use disorder (AUD) is a global public health problem and a leading cause of absenteeism and death worldwide (SAMHSA, 2018; SAMHSA, 2019; Global Status Report on Alcohol and Health, 2018). Psychedelics have long been proposed as a treatment for drug abuse, including AUD (Bogenschutz and Johnson, 2016). A metaanalysis of randomized controlled trials administering a single high-dose of lysergic acid diethylamide (LSD) for the treatment of AUD showed that 59% of LSD patients improved at initial followup compared to 38% of control patients (Krebs and Johansen, 2012). In a study investigating psychedelic-assisted treatment for AUD, acute treatment with psilocybin significantly decreased drinking days and heavy drinking days for 32 weeks compared to baseline (Bogenschutz et al, 2015). Studies from our research group have shown that ayahuasca, a hallucinogenic substance, blocks the development and expression of ethanol-induced behavioral sensitization (Oliveira-Lima et al, 2015) and the expression of conditioned place preference (CPP) to ethanol (Cata-Preta et al, 2018) in mice
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
