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Toxicity of ayahuasca after 28 days daily exposure and effects on monoamines and brain-derived neurotrophic factor (BDNF) in brain of Wistar rats.
Metabolic Brain Disease ( IF 3.6 ) Pub Date : 2020-02-27 , DOI: 10.1007/s11011-020-00547-w
Camila Schoueri Colaço 1 , Stefany Sousa Alves 1 , Luciana Marangni Nolli 1 , Willie Oliveira Pinheiro 2 , Danilo Gustavo Rodrigues de Oliveira 3 , Beatriz Werneck Lopes Santos 1 , Aline Pic-Taylor 2 , Márcia Renata Mortari 3 , Eloisa Dutra Caldas 1
Affiliation  

Ayahuasca is a hallucinogenic beverage that affects the serotonergic system and have therapeutic potential for many diseases and disorders, including depression and drug addiction. The objectives of this study were to evaluate the potential toxic effects of ayahuasca on rats after chronic exposure, and the levels of monoamines, their metabolites and the brain-derived neurotrophic factor (BDNF) in the brain. Female and male rats were treated orally for 28 days with H2O (control), fluoxetine (FLX), a selective serotonin reuptake inhibitor antidepressant, or ayahuasca (Aya) at doses of 0.5X, 1X and 2X the ritualistic dose (7 to 10 animals/group). Clinical, hematological and macroscopic results showed that ayahuasca was safe to the rats. Behavior tests conducted one hour after the last treatment showed that male rats from the Aya1 group explored the open field central area less than the control group, and the number of entries in the central area compared to total locomotion was also significantly lower in this group and in the FLX group. The hippocampus was removed for BDNF analysis and the remaining brain was used for monoamine analysis by HPLC-FL. Serotonin levels were significantly higher than control only in the Aya2 female group, while a significant reduction of its metabolite 5-HIAA was observed in the FLX group. Dopamine levels were similar among the experimental groups, but the levels of its metabolite DOPAC increased significantly in the Aya1 and Aya2 groups compared to controls, especially in females, and the DOPAC/dopamine turnover was significantly higher in Aya2 group. The levels of HVA, another dopamine metabolite, did not change with the treatments compared to controls, but HVA/DOPAC ratio was significantly lower in all ayahuasca male groups. Norepinephrine was not detected in any brain sample, and the levels of its metabolite MHPG did not change significantly among the groups. BDNF levels in the hippocampus were significantly higher in the FLX and Aya2 female groups compared to controls when expressed in relation to the total brain weight. The mechanisms involved in the increase in serotonin, dopamine turnover and BDNF levels observed in ayahuasca treated animals should be further investigated in specific brain areas.

中文翻译:

每天暴露 28 天后死藤水的毒性以及对 Wistar 大鼠脑中单胺和脑源性神经营养因子 (BDNF) 的影响。

Ayahuasca 是一种致幻饮料,会影响血清素系统,并具有治疗多种疾病和障碍的潜力,包括抑郁症和毒瘾。本研究的目的是评估死藤水对大鼠慢性暴露后的潜在毒性作用,以及大脑中单胺、其代谢物和脑源性神经营养因子 (BDNF) 的水平。雌性和雄性大鼠用 H2O(对照)、氟西汀 (FLX)、选择性血清素再摄取抑制剂抗抑郁药或死藤水 (Aya) 口服治疗 28 天,剂量为仪式剂量的 0.5 倍、1 倍和 2 倍(7 至 10 只动物) /团体)。临床、血液学和宏观结果表明死藤水对大鼠是安全的。在最后一次治疗后一小时进行的行为测试表明,Aya1 组雄性大鼠探索开阔场地中心区域的次数少于对照组,并且与总运动相比,该组的中心区域进入次数也显着减少,在 FLX 组。取出海马用于 BDNF 分析,剩余的大脑用于通过 HPLC-FL 进行单胺分析。仅在 Aya2 女性组中,血清素水平显着高于对照组,而在 FLX 组中观察到其代谢物 5-HIAA 显着减少。实验组之间的多巴胺水平相似,但与对照组相比,Aya1 和 Aya2 组其代谢物 DOPAC 的水平显着增加,尤其是在女性中,Aya2 组的 DOPAC/多巴胺周转率显着更高。与对照组相比,另一种多巴胺代谢物 HVA 的水平没有随着治疗而改变,但在所有死藤水男性组中,HVA/DOPAC 比率显着降低。在任何脑样本中均未检测到去甲肾上腺素,其代谢物 MHPG 的水平在各组之间没有显着变化。与对照组相比,FLX 和 Aya2 女性组海马中的 BDNF 水平在与总脑重量相关时显着更高。应在特定脑区进一步研究在死藤水治疗动物中观察到的血清素、多巴胺转换和 BDNF 水平增加的机制。但在所有死藤水男性组中,HVA/DOPAC 比率显着较低。在任何脑样本中均未检测到去甲肾上腺素,其代谢物 MHPG 的水平在各组之间没有显着变化。与对照组相比,FLX 和 Aya2 女性组海马中的 BDNF 水平在与总脑重量相关时显着更高。应在特定脑区进一步研究在死藤水治疗动物中观察到的血清素、多巴胺转换和 BDNF 水平增加的机制。但在所有死藤水男性组中,HVA/DOPAC 比率显着较低。在任何脑样本中均未检测到去甲肾上腺素,其代谢物 MHPG 的水平在各组之间没有显着变化。与对照组相比,FLX 和 Aya2 女性组海马中的 BDNF 水平在与总脑重量相关时显着更高。应在特定脑区进一步研究在死藤水治疗动物中观察到的血清素、多巴胺转换和 BDNF 水平增加的机制。与对照组相比,FLX 和 Aya2 女性组海马中的 BDNF 水平在与总脑重量相关时显着更高。应在特定脑区进一步研究在死藤水治疗动物中观察到的血清素、多巴胺转换和 BDNF 水平增加的机制。与对照组相比,FLX 和 Aya2 女性组海马中的 BDNF 水平在与总脑重量相关时显着更高。应在特定脑区进一步研究在死藤水治疗动物中观察到的血清素、多巴胺转换和 BDNF 水平增加的机制。
更新日期:2020-02-27
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