Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), Rua Botucatu, 862, Vila Clementino, São Paulo 04023062, Brazil; Centre for Applied Research in Mental Health and Addiction, Faculty of Health Sciences, Simon Fraser University, 515 W, Hastings Street, Vancouver, BC V6B 5K3, Canada; Interdisciplinary Cooperation for Ayahuasca Research and Outreach (ICARO), School of Medical Sciences, University of Campinas (UNICAMP), R. Tessália Vieira de Camargo, 126, Cidade Universitária, Campinas, São Paulo 13083-887, Brazil.
Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), Rua Botucatu, 862, Vila Clementino, São Paulo 04023062, Brazil.
Behav Brain Res. 2022 Jun 3;427:113878. doi: 10.1016/j.bbr.2022.113878. Epub 2022 Apr 1.
Considering the long-lasting effects of ayahuasca on the brain and emotional processing, the objective of this study was to evaluate the behavioural and neurobiological effects of repeated ayahuasca administration in an animal model of exploratory behaviour related to novel-environment anxiety. Male Wistar rats received water, 120, 240, 480 or 3600 mg/kg of resuspended freeze-dried ayahuasca by gavage once a day for 30 days; there was also a non-manipulated homecage group. One hour after the last administration, animals were placed individually in the open field for 20 min. We analysed the weight gain, the behavioural response through a stochastic analysis, and c-Fos immunoreactive levels in the hippocampus, amygdala, pre-frontal and barrel field cortex. Ayahuasca at 120 mg/kg increased ambulation, and at 3600 mg/kg decreased vertical exploration and reduced weight gain. Aya3600 had higher c-Fos expression in regions of the hippocampus and infralimbic cortex than homecage, water or aya120 groups. Water-receiving animals had less c-Fos expression in the anterior basolateral amygdala than others groups. Our results show different behavioural effects of ayahuasca: a stimulant-like effect in small doses, and decreased activity in extreme high-dose, probably due to adverse effects. Higher activation of areas involved in emotional processing and the serotonergic pathway adds to the neurobiological literature on repeated/chronic ingestion of ayahuasca. Our data do not support an anxiolytic effect of repeated ayahuasca related to exploring new anxiogenic-environment but suggest that low ayahuasca doses should be further studied. The absence of severe impairment and behavioural syntax alteration reinforce ayahuasca safety.
考虑到安非他命对大脑和情绪处理的持久影响，本研究的目的是在与新奇环境焦虑相关的探索行为的动物模型中评估重复给予安非他命的行为和神经生物学效应。雄性 Wistar 大鼠通过灌胃每天接受一次水、重新悬浮的冻干安非他命 120、240、480 或 3600mg/kg，还有一个非操作的家庭笼组。最后一次给药后 1 小时，将动物单独放置在开放场中 20 分钟。我们分析了体重增加、通过随机分析的行为反应以及海马、杏仁核、前额叶和桶状皮层中的 c-Fos 免疫反应性水平。安非他命 120mg/kg 增加了运动，而 3600mg/kg 减少了垂直探索并减少了体重增加。Aya3600 在海马体和下边缘皮质区域的 c-Fos 表达高于家庭笼、水或 aya120 组。接受水的动物前外侧杏仁核的 c-Fos 表达低于其他组。我们的结果显示了安非他命不同的行为效应：小剂量具有兴奋剂样作用，高剂量则活性降低，可能是由于不良反应。参与情感处理和 5-羟色胺能途径的区域的更高激活增加了关于重复/慢性摄入安非他命的神经生物学文献。我们的数据不支持重复安非他命与探索新的焦虑环境有关的抗焦虑作用，但表明应进一步研究低剂量的安非他命。没有严重的损伤和行为语法改变，这加强了安非他命的安全性。
