Cited by 215Psychedelics and Drug StudiesNeurotransmitter Receptor Influence on BehaviorHallucinations in medical conditions

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Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice

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Halberstadt, Adam L, Koedood, Liselore, Powell, Susan B, Geyer, Mark A·2011·Journal of Psychopharmacology

DOI 10.1177/0269881110388326PMC PMC3531560

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Abstract

Psilocin (4-hydroxy- N, N-dimethyltryptamine) is a hallucinogen that acts as an agonist at 5-HT 1A , 5-HT 2A , and 5-HT 2C receptors. Psilocin is the active metabolite of psilocybin, a hallucinogen that is currently being investigated clinically as a potential therapeutic agent. In the present investigation, we used a combination of genetic and pharmacological approaches to identify the serotonin (5-HT) receptor subtypes responsible for mediating the effects of psilocin on head twitch response (HTR) and the behavioral pattern monitor (BPM) in C57BL/6J mice. We also compared the effects of psilocin with those of the putative 5-HT 2C receptor-selective agonist 1-methylpsilocin and the hallucinogen and non-selective serotonin receptor agonist 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT). Psilocin, 1-methylpsilocin, and 5-MeO-DMT induced the HTR, effects that were absent in mice lacking the 5-HT 2A receptor gene. When tested in the BPM, psilocin decreased locomotor activity, holepoking, and time spent in the center of the chamber, effects that were blocked by the selective 5-HT 1A antagonist WAY-100635 but were not altered by the selective 5-HT 2C antagonist SB 242,084 or by 5-HT 2A receptor gene deletion. 5-MeO-DMT produced similar effects when tested in the BPM, and the action of 5-MeO-DMT was significantly attenuated by WAY-100635. Psilocin and 5-MeO-DMT also decreased the linearity of locomotor paths, effects that were mediated by 5-HT 2C and 5-HT 1A receptors, respectively. In contrast to psilocin and 5-MeO-DMT, 1-methylpsilocin (0.6–9.6 mg/kg) was completely inactive in the BPM. These findings confirm that psilocin acts as an agonist at 5-HT 1A , 5-HT 2A , and 5-HT 2C receptors in mice, whereas the behavioral effects of 1-methylpsilocin indicate that this compound is acting at 5-HT 2A sites but is inactive at the 5-HT 1A receptor. The fact that 1-methylpsilocin displays greater pharmacological selectivity than psilocin indicates that 1-methylpsilocin represents a potentially useful alternative to psilocybin for development as a potential therapeutic agent.

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Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance
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Authors: Halberstadt, A. L., Koedood, L., Powell, S. B., & Geyer, M. A.
Affiliations: Department of Psychiatry, University of California, La Jolla, CA, USA.
Corresponding author: Geyer, Mark A
ORCID: Halberstadt, Adam L
Powell, Susan B
Geyer, Mark A
Venue: Journal of Psychopharmacology
Publisher: SAGE Publications
Published: 2010-12-08
Volume: 25
Issue: 11
Pages: 1548-1561
ISSN: 0269-8811 (ISSN-L)
1461-7285
DOI: 10.1177/0269881110388326
PMC: PMC3531560
OpenAlex: W2107441654
Cited by: 213
References: 65
Citations by year: 2026: 24 · 2025: 32 · 2024: 31 · 2023: 20 · 2022: 18 · 2021: 8 · 2020: 11 · 2019: 9 · 2018: 13 · 2017: 5 · 2016: 10 · 2015: 8 · 2014: 7 · 2013: 8 · 2012: 4
FWCI: 5.96
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: University of California, San Diego
National Institute of Mental Health
National Institute on Drug Abuse (F32DA025412, R01DA002925)
Topics: Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
Keywords: psilocin, psilocybin, 5-MeO-DMT, serotonin receptors, 5-HT1A receptor, 5-HT2A receptor, 5-HT2C receptor, head-twitch response, locomotor activity, WAY-100635, SB242084, receptor selectivity, hallucinogens
MeSH terms: Animals, Behavior, Hallucinogens, Male, Methoxydimethyltryptamines, Mice, Inbred C57BL, Motor Activity, Piperazines, Psilocybin, Pyridines, Receptors, Serotonin, Serotonin Antagonists, Mice, Knockout, Mice

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Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice

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