Validation of the forced swim test in Drosophila, and its use to demonstrate psilocybin has long-lasting antidepressant-like effects in flies.

Validation of the forced swim test in Drosophila, and its use to demonstrate psilocybin has long-lasting antidepressant-like effects in flies.
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DOI:
10.1038/s41598-022-14165-2
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发表时间:
2022-06-15
期刊:
影响因子:
4.6
通讯作者:
Nichols, C. D.
Nichols, C. D.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hibicke, M.;Nichols, C. D.

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裸盖菇素已被证明是一种强大的,持久的抗抑郁药在人类临床试验和啮齿动物模型。虽然啮齿类动物通常被用来模拟精神疾病,但果蝇具有与哺乳动物相似的神经递质系统,并且许多类似的大脑结构涉及类似的行为。强迫游泳试验(FST),这已被广泛用于评估化合物的抗抑郁疗效,最近已适用于果蝇。苍蝇FST有可能成为一个具有成本效益的,高通量的检测方法,用于评估潜在的抗抑郁药。在这项研究中,我们使用甲基苯丙胺、DL-α-甲基酪氨酸和抗抑郁药西酞普兰验证了果蝇FST。虽然甲基苯丙胺和DL-α-甲基酪氨酸改变了果蝇活动监测系统(DAMS)中的整体运动活动,但它们对FST中的不动性测量没有显著影响。相反,慢性西酞普兰降低了两种性别的FST中的不动性,而没有增加DAMS活性。我们使用经验证的FST来评估高(3.5 mM)和低(0.03 mM)剂量的裸盖菇素的抗抑郁样作用。这两种剂量的裸盖菇素显着降低措施的不动性在男性苍蝇,但不是女性。0.03 mM的效应量与慢性西酞普兰相当,3.5 mM的效应量约为慢性西酞普兰的两倍。
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.
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