松素-NMDAR调节剂的协同行为和神经可塑性影响的管理
Tom Ben-Tal1, Ilana Pogodin1, Alexander Botvinnik1
1Hadassah BrainLabs Center for Psychedelic Research, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.
Translational psychiatry
|June 13, 2025
概括
将psilocybin与N-甲基-D-酸盐受体调节剂D-或D-环素结合使用可能会增强神经精神疾病的治疗潜力. 这些组合减少了迷幻效应,并增加了小鼠的神经可塑性,这表明安全性和有效性得到了改善.
科学领域:
- 神经科学是一个神经科学.
- 心理药理学 心理药理学
- 神经生物学 神经生物学 神经生物学
背景情况:
- 血清色精神药物 (SP) 对神经精神疾病具有治疗前景,但具有剂量限制的不良影响.
- N-甲基-D-酸盐受体 (NMDAR) 调制剂可能提供增强SP有效性和安全性的补充机制.
研究的目的:
- 为了研究将psilocybin (PSIL) 与NMDAR调节剂D-serine (DSER) 和D-cycloserine (DCS) 结合在一起的协同效应.
- 评估这些组合对小鼠的幻觉类效应,抗精神病类效应和神经可塑性标记物的影响.
主要方法:
- 实验使用ICR雄性小鼠进行.
- 评估头部抽反应 (HTR) 作为幻觉效应的衡量标准.
- 评估了MK-801诱导的超位动,以模拟抗精神病作用.
- 在关键大脑区域分析了与神经可塑性相关的突触蛋白水平 (GAP43,PSD95).
主要成果:
- PSIL显著增加了HTR,通过同时服用DSER或DCS,剂量依赖地减少了HTR.
- 使用PSIL与DSER或DCS相结合,显著减轻了MK-801引起的过敏.
- 在海马体中,PSIL-DSER增强了GAP43和整体突触蛋白表达.
- 在多个大脑区域中,PSIL-DCS提高了PSD95水平,这表明了synaptogenic协同作用.
结论:
- 同时使用DSER或DCS与西可以减轻副作用并增强神经可塑性.
- 这些组合有可能优化色胺类精神药物的治疗应用.
- 需要进一步的研究来完善协议并评估临床可翻译性.
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