Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA, USA.
Sci Rep. 2022 Jun 15;12(1):10019. doi: 10.1038/s41598-022-14165-2.
Psilocybin has been shown to be a powerful, long-lasting antidepressant in human clinical trials and in rodent models. Although rodents have commonly been used to model psychiatric disorders, Drosophila have neurotransmitter systems similar to mammals and many comparable brain structures involved in similar behaviors. The forced swim test (FST), which has been used extensively to evaluate compounds for antidepressant efficacy, has recently been adapted for Drosophila. The fly FST has potential to be a cost-effective, high-throughput assay for evaluating potential antidepressants. For this study we pharmacologically validated the fly FST using methamphetamine, DL-α-methyltyrosine, and the antidepressant citalopram. While methamphetamine and DL-α-methyltyrosine altered overall locomotor activity in the Drosophila Activity Monitor System (DAMS), they had no significant impact on measures of immobility in the FST. Conversely, chronic citalopram decreased measures of immobility in the FST in both sexes without increasing DAMS activity. We used the validated FST to evaluate the antidepressant-like effects of high (3.5 mM) and low (0.03 mM) doses of psilocybin. Both doses of psilocybin significantly reduced measures of immobility in male flies, but not females. 0.03 mM had an effect size comparable to chronic citalopram, and 3.5 mM had an effect size approximately twice that of chronic citalopram.
裸盖菇素在人类临床试验和啮齿动物模型中已被证明是一种强大且持久的抗抑郁药。尽管啮齿动物通常被用于模拟精神疾病，但果蝇具有与哺乳动物相似的神经递质系统，并且许多相似的大脑结构参与相似的行为。强迫游泳测试（FST）已被广泛用于评估抗抑郁功效的化合物，最近已被改编为用于果蝇的测试。果蝇 FST 具有成为评估潜在抗抑郁药的成本效益高、高通量测定法的潜力。在这项研究中，我们使用安非他命、DL-α-甲基酪氨酸和抗抑郁药西酞普兰对果蝇 FST 进行了药理学验证。虽然安非他命和 DL-α-甲基酪氨酸改变了果蝇活动监测系统（DAMS）中整体运动活动，但它们对 FST 中不动性的测量没有显著影响。相反，西酞普兰慢性给药可降低两性果蝇 FST 中不动性的测量值，而不会增加 DAMS 活性。我们使用经过验证的 FST 来评估高（3.5 mM）和低（0.03 mM）剂量裸盖菇素的抗抑郁样作用。两种剂量的裸盖菇素均显著降低了雄性果蝇的不动性测量值，但对雌性果蝇没有影响。0.03 mM 的作用大小与慢性西酞普兰相当，而 3.5 mM 的作用大小约为慢性西酞普兰的两倍。
