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-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). 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. 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.
- MeSH
- antagonisté serotoninu farmakologie MeSH
- estrální cyklus fyziologie MeSH
- halucinogeny aplikace a dávkování farmakologie MeSH
- krysa rodu rattus MeSH
- lokomoce účinky léků MeSH
- potkani Wistar MeSH
- psilocybin aplikace a dávkování analogy a deriváty farmakologie MeSH
- receptory serotoninové účinky léků metabolismus MeSH
- serotonin metabolismus MeSH
- sexuální faktory MeSH
- úleková reakce účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- MeSH
- anestetika * farmakologie terapeutické užití MeSH
- antidepresiva * farmakokinetika terapeutické užití MeSH
- deprese farmakoterapie MeSH
- ketamin * dějiny farmakologie škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- poruchy spojené s užíváním psychoaktivních látek MeSH
- psychotropní léky * škodlivé účinky MeSH
- receptory N-methyl-D-aspartátu agonisté terapeutické užití MeSH
- schizofrenie MeSH
- výzkum MeSH
- Check Tag
- lidé MeSH
