Sex differences and serotonergic mechanisms in the behavioural effects of psilocin
Filip Tylš, Tomáš Páleníček, Lukáš Kadeřábek, Michaela Lipski, Anna Kubešová, Jiřı́ Horáček
Behavioural Pharmacology October 13, 2015 DOI: 10.1097/fbp.0000000000000198 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male and female rats |
| Intervention | Psilocin |
| Dose | Psilocin 0.25, 1, 4 mg/kg; WAY100635 1 mg/kg; MDL100907 0.5 mg/kg; SB215505 1 mg/kg; SB242084 1 mg/kg |
| Measures | Open-field test, prepulse inhibition (PPI) of acoustic startle |
| Topics | Psilocybin Serotonin |
| Keywords | Prepulse inhibition Receptor antagonist Pharmacology Open field 5-HT Receptor Serotonin antagonists |
| Citations | 86 |
| Key findings | Psilocin induces dose-dependent inhibition of locomotion and suppression of normal behavior, with effects more pronounced in male rats; locomotion inhibition is normalized by 5-HT 1A and 5-HT 2B/C antagonists, but prepulse inhibition is not significantly affected by these antagonists. |
Abstract
Psilocybin has recently attracted a great deal of attention as a clinical research and therapeutic tool. The aim of this paper is to bridge two major knowledge gaps regarding its behavioural pharmacology – sex differences and the underlying receptor mechanisms. We used psilocin (0.25, 1 and 4 mg/kg), an active metabolite of psilocybin, in two behavioural paradigms – the open-field test and prepulse inhibition (PPI) of the acoustic startle reaction. Sex differences were evaluated with respect to the phase of the female cycle. The contribution of serotonin receptors in the behavioural action was tested in male rats with selective serotonin receptor antagonists: 5-HT 1A receptor antagonist (WAY100635 1 mg/kg), 5-HT 2A receptor antagonist (MDL100907 0.5 mg/kg), 5-HT 2B receptor antagonist (SB215505 1 mg/kg) and 5-HT 2C receptor antagonist (SB242084 1 mg/kg). Psilocin induced dose-dependent inhibition of locomotion and suppression of normal behaviour in rats (behavioural serotonin syndrome, impaired PPI). The effects were more pronounced in male rats than in females. The inhibition of locomotion was normalized by 5-HT 1A and 5-HT 2B/C antagonists; however, PPI was not affected significantly by these antagonists. Our findings highlight an important issue of sex-specific reactions to psilocin and that apart from 5-HT 2A -mediated effects 5-HT 1A and 5-HT 2C/B receptors also play an important role. These findings have implications for recent clinical trials.
Comparable studies
Other preclinical and animal studies on serotonin, 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 | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 75
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin Journal of Psychopharmacology November 4, 2020
- Structure–Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice ACS Pharmacology & Translational Science November 2, 2022
- Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat Acta Neuropsychiatrica May 20, 2019
- Rethinking Therapeutic Strategies for Anorexia Nervosa: Insights From Psychedelic Medicine and Animal Models Frontiers in Neuroscience February 4, 2020
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Cites 29
- Serotonin research: contributions to understanding psychoses TIPS - Trends in Pharmacological Sciences August 1, 2008
- Prediction of Psilocybin Response in Healthy Volunteers PLoS One February 17, 2012
- Psychedelics and the Human Receptorome PLoS One 2010
- Psilocybin – Summary of knowledge and new perspectives European Neuropsychopharmacology December 17, 2013
- Differential effects of 5-hydroxytryptamine1a selective drugs on the 5-HT behavioral syndrome. Pharmacology, Biochemistry, and Behavior June 1, 1986
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