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dc.contributor.authorErkizia Santamaría, Inés
dc.contributor.authorAllés Pascual, Roser
dc.contributor.authorHorrillo Furundarena, Igor ORCID
dc.contributor.authorMeana Martínez, José Javier ORCID
dc.contributor.authorOrtega Calvo, Jorge
dc.date.accessioned2022-11-22T17:56:02Z
dc.date.available2022-11-22T17:56:02Z
dc.date.issued2022-10
dc.identifier.citationBiomedicine & Pharmacotherapy 154 : (2022) // Article ID 113612es_ES
dc.identifier.issn0753-3322
dc.identifier.issn1950-6007
dc.identifier.urihttp://hdl.handle.net/10810/58494
dc.description.abstractThe psychedelic 5-HT2A receptor (5HT2AR) agonist psilocybin (or the active metabolite psilocin) has emerged as potential useful drug for various neuropsychiatric diseases, with a rapid onset of therapeutic activity. However, the mechanisms responsible for such effects remain incompletely characterized. We aimed to study in vitro pharmacological profile and in vivo acute mechanism of psilocin/psilocybin. Competition binding studies with psilocin were performed in brain and cell cultures. The role of 5HT2AR, 5-HT2C receptors (5HT2CR) and 5-HT1A receptors (5HT1AR) on the psychosis-like head-twitch response (HTR) and on body temperature in mice after psilocybin administration were evaluated. Psilocin showed similar affinities for 5HT2AR (Ki: 120-173 nM), 5HT2CR (Ki: 79-311 nM) and 5-HT1AR (Ki: 152-146 nM) in human and mice brain. Psilocybin induced a dosedependent HTR (maximal effect 17.07 +/- 1.31 at 1 mg/kg i.p.) that was completely suppressed by the 5HT2AR antagonist MDL11939 (1 mg/kg). Higher doses of psilocybin (3 mg/kg) induced lower HTR (9.00 +/- 0.53). The 5HT2CR antagonist SB242084 (0.1 mg/kg) increased HTR exerted by psilocybin (3 mg/kg). Psilocybin significantly raised core body temperature at low dose (0.125 mg/kg) (Emax=0.67 +/- 0.15 degrees C), whereas a significant decrease was induced by doses over 1 mg/kg (Emax = -1.31 +/- 0.16 degrees C). Pre-treatment with the 5HT1AR antagonist WAY100635 reversed the decrease of body temperature after psilocybin (1 mg/kg), causing hyperthermia (Emax = 0.94 +/- 0.26 degrees C). The present work provides key findings on the 5HT2AR, 5-HT2CR and 5HT1AR involvement in the acute central effects of psilocybin. The results may be relevant for understanding the mechanism of action underlying the therapeutic effects and side effects of this psychedelic drug.es_ES
dc.description.sponsorshipThis work was supported by Grant PID2021-123508OB-I00, funded by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe, by the Basque Government (IT-1211-19; IT-1512-22) , by CIBER-Consorcio Centro de Investigacion Biomedica en Red- (CB/07/09/0008) , Instituto de Salud Carlos III, and by Fundacion Vital Funda-zioa (VITAL21/17) . IE-S received a predoctoral fellowship from the UPV/EHU.es_ES
dc.language.isoenges_ES
dc.publisherElsevieres_ES
dc.relationinfo:eu-repo/grantAgreement/MICINN/PID2021-123508OB-I00es_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/*
dc.subjectpsilocybines_ES
dc.subject5-HT 1A receptorses_ES
dc.subject5-HT 2A receptorses_ES
dc.subject5-HT 2C receptorses_ES
dc.subjecthead -twitch responsees_ES
dc.subjectbody temperaturees_ES
dc.titleSerotonin 5-HT2A, 5-HT2c and 5-HT1A receptor involvement in the acute effects of psilocybin in mice. In vitro pharmacological profile and modulation of thermoregulation and head-twich responsees_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.holder© 2022 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).es_ES
dc.rights.holderAtribución-NoComercial-SinDerivadas 3.0 España*
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0753332222010010?via%3Dihubes_ES
dc.identifier.doi10.1016/j.biopha.2022.113612
dc.departamentoesFarmacologíaes_ES
dc.departamentoeuFarmakologiaes_ES


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© 2022 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as © 2022 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).