Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat
In the Flinders Sensitive Line rat model of depression, psilocin and psilocybin produced no antidepressant-like effects in the forced swim test and did not alter locomotor activity, despite FSL rats showing the expected increased immobility versus controls. The authors suggest the FSL model and FST may be inappropriate for translational studies of psilocybin’s antidepressant actions.
Abstract
Objective
Psilocybin is a serotonin receptor agonist with a therapeutic potential for treatment-resistant depression and other psychiatric illnesses. We investigated whether the administration of psilocybin had an antidepressant-like effect in a rat model of depression.
Methods
Using the Flinders Sensitive Line (FSL) rat model of depression, we assessed the antidepressant-like effect of psilocin and psilocybin, measured as a reduction in immobility time in the forced swim test (FST). We measured locomotor activity in an open field test (OFT) to control for stimulant properties of the drugs. We performed a set of experiments to test different doses, treatment paradigms, and timing of the tests in relation to the drug administration.
Results
Psilocin and psilocybin showed no effect on immobility, struggling, or swimming behaviour in the FST and no effect on locomotor activity in the OFT. FSL rats did show significantly more immobility than their control strain, the Flinders Resistant Line, as expected.
Conclusion
Psilocin and psilocybin showed no antidepressant-like effect in the FSL rats, despite a positive effect in humans. This suggests that other animal models of depression and other behavioural tests may be more appropriate for translational studies in the effects of psilocybin.
Research Summary of 'Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat'
Introduction
Depression is a major global health problem with substantial unmet needs: current pharmacological and psychological treatments leave a sizeable minority of patients non-responsive, have delayed onset for many, and carry high relapse rates. Re-purposing older compounds with novel mechanisms has therefore attracted interest. Psilocybin, a serotonergic psychedelic found in 'magic mushrooms', has shown promising, rapid and sustained antidepressant effects in small human trials when administered alongside psychological support, but its neurobiological mechanisms remain poorly understood and require translational animal work to explore causal pathways. Jefsen and colleagues set out to test whether psilocybin or its active metabolite psilocin produce antidepressant-like effects in an established rat model of depression, the Flinders Sensitive Line (FSL). Using immobility in the forced swim test (FST) as the primary behavioural readout and the Flinders Resistant Line (FRL) as a control strain, the investigators conducted a series of experiments varying dose, treatment paradigm and timing to assess whether psilocybin/psilocin reduce immobility consistent with an antidepressant-like effect. They hypothesised that drug treatment would lower immobility in FSL rats compared with saline-treated FSL controls.
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Study Details
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- APA Citation
Jefsen, O., Højgaard, K., Christiansen, S. L., Elfving, B., Nutt, D. J., Wegener, G., & Müller, H. K. (2019). Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat. Acta Neuropsychiatrica, 31(04), 213-219. https://doi.org/10.1017/neu.2019.15
References (13)
Papers cited by this study that are also in Blossom
Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A. et al. · Journal of Psychopharmacology (2015)
Buchborn, T., Schröder, H., Höllt, V. et al. · Journal of Psychopharmacology (2014)
Cameron, L. P., Benson, C. J., Dunlap, L. E. · ACS Chemical Neuroscience (2018)
Carhart-Harris, R. L., Bolstridge, M., Rucker, J. et al. · Lancet Psychiatry (2016)
Fond, G., Loundou, A., Macgregor, A. et al. · Psychopharmacology (2014)
Gonza ´lez-Maeso, J., Weisstaub, N. V., Zhou, M. et al. · Neuron (2007)
Horsley, R. R., Páleníček, T., Kolin, J. et al. · Behavioural Pharmacology (2018)
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P. et al. · Journal of Psychopharmacology (2014)
Preller, K. H., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)
Quednow, B. B., Kometer, M., Geyer, M. A. et al. · Neuropsychopharmacology (2011)
Show all 13 referencesShow fewer
Ross, S., Bossis, A. P., Guss, J. et al. · Journal of Psychopharmacology (2016)
Tylš, F., Páleníček, T., Kadeřábek, L. et al. · Behavioural Pharmacology (2016)
Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F. I., Bäbler, A. et al. · NeuroReport (1998)
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