Validation of the forced swim test in Drosophila, and its use to demonstrate psilocybin has long-lasting antidepressant-like effects in flies
Meghan Hibicke, Charles D. Nichols
Scientific Reports June 15, 2022 DOI: 10.1038/s41598-022-14165-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical pharmacological validation and behavioral study Peer reviewed |
|---|---|
| Population | Drosophila melanogaster (fruit flies) |
| Interventions | Psilocybin Methamphetamine DL-α-methyltyrosine Citalopram |
| Dose | 3.5 mM, 0.03 mM |
| Duration | Chronic (for citalopram; duration not specified for psilocybin) |
| Topics | Psilocybin |
| Keywords | Antidepressant Behavioural despair test Drosophila subgenus Drosophila melanogaster Test biology Pharmacology |
| Citations | 25 |
| Key points | Both high and low doses of psilocybin significantly reduced immobility measures in male fruit flies in the forced swim test, with the high dose showing an effect size twice that of chronic citalopram, but no significant effect in females. |
Abstract
Abstract 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.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 11
- The evolution and ecology of psilocybin in nature. Fungal Genetics and Biology June 1, 2023
- A Single Administration of Psilocybin Persistently Rescues Cognitive Deficits Caused by Adolescent Chronic Restraint Stress Without Long-Term Changes in Synaptic Protein Gene Expression in a Rat Experimental System with Translational Relevance to Depression. Psychedelic Medicine March 1, 2023
- Unraveling psilocybin's therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression. Psychopharmacology July 4, 2024
- Probing the antidepressant potential of psilocybin: integrating insight from human research and animal models towards an understanding of neural circuit mechanisms. Psychopharmacology 2023
- Effect of psilocybin on decision-making and motivation in the healthy rat. Behavioural Brain Research February 25, 2023
and 6 more in the library
Cites 7
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
- Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression ACS Chemical Neuroscience March 5, 2020
and 2 more in the library