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Cited by 13Psychedelics and Drug StudiesNeurotransmitter Receptor Influence on BehaviorAlkaloids: synthesis and pharmacology

Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms

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Jiang, Xi-Ling, Shen, Hong-Wu, Yu, Ai-Ming·2016·Pharmacological Reports
DOI 10.1016/j.pharep.2016.01.008PMC PMC4848137
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Abstract

Background 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are indolealkylamine (IAA) drugs often abused together. Our recent studies have revealed the significant effects of co-administered harmaline, a monoamine oxidase inhibitor (MAOI), on 5-MeO-DMT pharmacokinetics and thermoregulation. This study was to delineate the impact of harmaline and 5-MeO-DMT on home-cage activity in mouse models, as well as the contribution of serotonin (5-HT) receptors. Methods Home-cage activities of individual animals were monitored automatically in the home cages following implantation of telemetry transmitters and administration of various doses of IAA drugs and 5-HT receptor antagonists. Area under the effect curve (AUEC) of mouse activity values were calculated by trapezoidal rule. Results High dose of harmaline (15mg/kg, ip) alone caused an early-phase (0-45min) hypoactivity in mice that was fully attenuated by 5-HT1A receptor antagonist WAY-100635, whereas a late-phase (45-180min) hyperactivity that was reduced by 5-HT2A receptor antagonist MDL-100907. 5-MeO-DMT (10 and 20mg/kg, ip) alone induced biphasic effects, an early-phase (0-45min) hypoactivity that was completely attenuated by WAY-100635, and a late-phase (45-180min) hyperactivity that was fully suppressed by MDL-100907. Interestingly, co-administration of MAOI harmaline (2-15mg/kg) with a subthreshold dose of 5-MeO-DMT (2mg/kg) induced excessive hyperactivities at late phase (45-180min) that could be abolished by either WAY-100635 or MDL-100907. Conclusions Co-administration of MAOI with 5-MeO-DMT provokes excessive late-phase hyperactivity, which involves the activation of both 5-HT1A and 5-HT2A receptors.

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  • Treatment of rats with harmaline (2-15 mg/kg, i.p.) greatly potentiated the behavioral effects of 5-MeO-DMT, causing hyperactivity at a subthreshold dose of the tryptamine compound (2 mg/kg, i.p.).

    “For example, treatment of rats with harmaline (46) (2–15 mg/kg, i.p.) greatly potentiated the behavioral effects of 5-MeO-DMT (15), causing hyperactivity at a subthreshold dose of the tryptamine compound (2 mg/kg, i.p.) [132].”

    From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [132]

    The Results section reports that harmaline (2–15 mg/kg) combined with a subthreshold 2 mg/kg dose of 5-MeO-DMT increased late-phase home-cage activity two- to threefold. The study tested mice, not rats, so the species attributed to the source is incorrect. Page numbers were not supplied in the copy. (LLM, conf=0.88)

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Authors
Jiang, X.-L., Shen, H.-W., & Yu, A.-M.
Affiliations
  • University at Buffalo, State University of New York (US)
  • University of California Davis Medical Center (US)
Corresponding author
Yu, Ai-Ming
ORCID
Yu, Ai-Ming
Venue
Pharmacological Reports
Publisher
Springer Science and Business Media LLC
Published
2016-06
Volume
68
Issue
3
Pages
608-615
ISSN
1734-1140 (ISSN-L)
DOI
10.1016/j.pharep.2016.01.008
PMC
PMC4848137
OpenAlex
W2278540383
Cited by
13
References
5
Citations by year
2026: 1 · 2025: 2 · 2022: 2 · 2021: 3 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 1
FWCI
2.23
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Pharmacological Reports (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
National Institutes of Health (NIH) (R01DA021172)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Alkaloids: synthesis and pharmacology
Keywords
harmaline, monoamine oxidase A inhibitors, home cage activity, hyperactivity, serotonin receptors, 5-HT1A receptor, 5-HT2A receptor, WAY-100635, biphasic effect, indolealkylamines, drug co-administration
MeSH terms
Animals, Dose-Response Relationship, Drug, Drug Synergism, Fluorobenzenes, Harmaline, Hyperkinesis, Male, Methoxydimethyltryptamines, Monoamine Oxidase Inhibitors, Motor Activity, Piperazines, Piperidines, Pyridines, Hypokinesia, Mice, Serotonin 5-HT1 Receptor Agonists, Serotonin 5-HT2 Receptor Agonists

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