Alcohol use disorder needs more effective treatments because relapse rates remain high. Psychedelics, such as ayahuasca, have been used to treat substance use disorders. Our study aimed to evaluate the effects of ayahuasca on ethanol-induced behavioral sensitization (EIBS). Swiss mice received 2.2 g/kg ethanol or saline IP injections every other day across nine days (D1, D3, D5, D7, and D9), and locomotor activity was evaluated 10 min after each injection. Then, animals were treated daily with ayahuasca (corresponding to 1.76 mg/kg of N,N-dimethyltryptamine, DMT) or water by oral gavage for eight consecutive days. On the seventh day, mice were evaluated in the elevated plus maze. Then, mice were challenged with a single dose of ethanol to measure their locomotor activity. Dopamine receptors, serotonin receptors, dynorphin, and prodynorphin levels were quantified in the striatum and hippocampus by blot analysis. Repeated ethanol administration resulted in EIBS. However, those animals treated with ayahuasca had an attenuated EIBS. Moreover, ayahuasca reduced the anxiogenic response to ethanol withdrawal and prevented the ethanol-induced changes on 5-HT1a receptor and prodynorphin levels in the hippocampus and reduced ethanol effects in the dynorphin/prodynorphin ratio levels in the striatum. These results suggest a potential application of ayahuasca to modulate the neuroplastic changes induced by ethanol.

酒精使用障碍需要更有效的治疗，因为复发率仍然很高。迷幻药，如死藤水，已被用于治疗物质使用障碍。我们的研究旨在评估死藤水对乙醇诱导的行为致敏 (EIBS) 的影响。瑞士小鼠在 9 天内（D1、D3、D5、D7 和 D9）每隔一天接受 2.2 g/kg 乙醇或盐水腹腔注射，每次注射后 10 分钟评估运动活动。然后，通过连续八天的口服管饲法，每天用死藤水（相当于 1.76 mg/kg 的 N,N-二甲基色胺，DMT）或水对动物进行治疗。第 7 天，小鼠在高架十字迷宫中进行评估。然后，用单剂量的乙醇对小鼠进行挑战，以测量它们的运动活动。多巴胺受体、血清素受体、强啡肽、通过印迹分析定量纹状体和海马中的强啡肽原水平。重复乙醇给药导致EIBS。然而，那些用死藤水处理的动物的 EIBS 减弱了。此外，死藤水降低了对乙醇戒断的焦虑反应，并防止了乙醇诱导的海马 5-HT1a 受体和强啡肽原水平的变化，并降低了乙醇对纹状体中强啡肽/强啡肽原比例水平的影响。这些结果表明死藤水在调节乙醇诱导的神经可塑性变化方面的潜在应用。ayahuasca 降低了对乙醇戒断的焦虑反应，并防止了乙醇诱导的海马 5-HT1a 受体和强啡肽水平的变化，并降低了乙醇对纹状体中强啡肽/强啡肽比例水平的影响。这些结果表明死藤水在调节乙醇诱导的神经可塑性变化方面的潜在应用。ayahuasca 降低了对乙醇戒断的焦虑反应，并防止了乙醇诱导的海马 5-HT1a 受体和强啡肽水平的变化，并降低了乙醇对纹状体中强啡肽/强啡肽比例水平的影响。这些结果表明死藤水在调节乙醇诱导的神经可塑性变化方面的潜在应用。