Sex differences and serotonergic mechanisms in the behavioural effects of psilocin

This rodent study examines the behavioral pharmacology of psilocybin (0.25, 1, 4 mg/kg) with respect to sex differences and the underlying receptor mechanisms. Psilocin produced dose-dependent inhibition of locomotor activity, social behaviors, and startle reflex, which was mediated by the 5-HT2A, 5-HT1A, and 5-HT2C/B receptors, and more pronounced in male compared to female rats.

Abstract

Introduction: 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.

Methods: 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-HT1A receptor antagonist (WAY100635 1 mg/kg), 5-HT2A receptor antagonist (MDL100907 0.5 mg/kg), 5-HT2B receptor antagonist (SB215505 1 mg/kg) and 5-HT2C receptor antagonist (SB242084 1 mg/kg).

Results: 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-HT1A and 5-HT2B/C antagonists; however, PPI was not affected significantly by these antagonists.

Results: Our findings highlight an important issue of sex-specific reactions to psilocin and that apart from 5-HT2A-mediated effects 5-HT1A and 5-HT2C/B receptors also play an important role. These findings have implications for recent clinical trials.

Authors: Filip Tylš, Tomáš Páleníček, Lukáš Kadeřábek, Michaela Lipski, Anna Kubešová & Jiří Horáček

Summary of Sex differences and serotonergic mechanisms in the behavioural effects of psilocin

Introduction

Psilocin is an active metabolite of the naturally occurring tryptamine hallucinogen psilocybin, and has been recently gained interest as a potential therapeutic agent for depression in terminal patients, obsessive – compulsive disorder, addictions and cluster headaches.

Psilocybin can cause profound changes in perception, altered self-perception, derealization and depersonalization, thought content disorder, and sometimes also anxiety. Preclinical experiments cannot detect these effects, but can reveal other effects, such as changes in arousal, exploration, anxiety, habituation, etc.

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Study details

Compounds studied
Psilocybin

Topics studied
Neuroscience

Study characteristics
Animal Study

Authors

Authors associated with this publication with profiles on Blossom

Tomáš Páleníček
Tomas Palinek is a researcher and psychiatrist in the Czech Republic where he studies a variety of psychedelics at the NIHM.

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