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

Xi Ling Jiang, Hong Wu Shen, Aiming Yu

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 (15 mg/kg, ip) alone caused an early-phase (0-45 min) hypoactivity in mice that was fully attenuated by 5-HT1A receptor antagonist WAY-100635, whereas a late-phase (45-180 min) hyperactivity that was reduced by 5-HT2A receptor antagonist MDL-100907. 5-MeO-DMT (10 and 20 mg/kg, ip) alone induced biphasic effects, an early-phase (0-45 min) hypoactivity that was completely attenuated by WAY-100635, and a late-phase (45-180 min) hyperactivity that was fully suppressed by MDL-100907. Interestingly, co-administration of MAOI harmaline (2-15 mg/kg) with a subthreshold dose of 5-MeO-DMT (2 mg/kg) induced excessive hyperactivities at late phase (45-180 min) 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.

Original languageEnglish (US)
Pages (from-to)608-615
Number of pages8
JournalPharmacological Reports
Volume68
Issue number3
DOIs
StatePublished - Jun 1 2016

Fingerprint

Methoxydimethyltryptamines
Harmaline
Monoamine Oxidase Inhibitors
Monoamine Oxidase
Receptor, Serotonin, 5-HT2A
Serotonin Receptors
Serotonin 5-HT1 Receptor Antagonists
Serotonin 5-HT2 Receptor Antagonists
Telemetry
Serotonin Antagonists
Receptor, Serotonin, 5-HT1A
Body Temperature Regulation
Pharmaceutical Preparations
Area Under Curve
Pharmacokinetics

Keywords

  • 5-HT receptor
  • 5-MeO-DMT
  • Activity
  • Harmaline
  • MAOI

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{a66feef0bac64b2d85779b65c719bfc0,
title = "Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms",
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 (15 mg/kg, ip) alone caused an early-phase (0-45 min) hypoactivity in mice that was fully attenuated by 5-HT1A receptor antagonist WAY-100635, whereas a late-phase (45-180 min) hyperactivity that was reduced by 5-HT2A receptor antagonist MDL-100907. 5-MeO-DMT (10 and 20 mg/kg, ip) alone induced biphasic effects, an early-phase (0-45 min) hypoactivity that was completely attenuated by WAY-100635, and a late-phase (45-180 min) hyperactivity that was fully suppressed by MDL-100907. Interestingly, co-administration of MAOI harmaline (2-15 mg/kg) with a subthreshold dose of 5-MeO-DMT (2 mg/kg) induced excessive hyperactivities at late phase (45-180 min) 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.",
keywords = "5-HT receptor, 5-MeO-DMT, Activity, Harmaline, MAOI",
author = "Jiang, {Xi Ling} and Shen, {Hong Wu} and Aiming Yu",
year = "2016",
month = "6",
day = "1",
doi = "10.1016/j.pharep.2016.01.008",
language = "English (US)",
volume = "68",
pages = "608--615",
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issn = "1734-1140",
publisher = "Polish Academy of Sciences Publishing House",
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}

TY - JOUR

T1 - Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms

AU - Jiang, Xi Ling

AU - Shen, Hong Wu

AU - Yu, Aiming

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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 (15 mg/kg, ip) alone caused an early-phase (0-45 min) hypoactivity in mice that was fully attenuated by 5-HT1A receptor antagonist WAY-100635, whereas a late-phase (45-180 min) hyperactivity that was reduced by 5-HT2A receptor antagonist MDL-100907. 5-MeO-DMT (10 and 20 mg/kg, ip) alone induced biphasic effects, an early-phase (0-45 min) hypoactivity that was completely attenuated by WAY-100635, and a late-phase (45-180 min) hyperactivity that was fully suppressed by MDL-100907. Interestingly, co-administration of MAOI harmaline (2-15 mg/kg) with a subthreshold dose of 5-MeO-DMT (2 mg/kg) induced excessive hyperactivities at late phase (45-180 min) 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.

AB - 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 (15 mg/kg, ip) alone caused an early-phase (0-45 min) hypoactivity in mice that was fully attenuated by 5-HT1A receptor antagonist WAY-100635, whereas a late-phase (45-180 min) hyperactivity that was reduced by 5-HT2A receptor antagonist MDL-100907. 5-MeO-DMT (10 and 20 mg/kg, ip) alone induced biphasic effects, an early-phase (0-45 min) hypoactivity that was completely attenuated by WAY-100635, and a late-phase (45-180 min) hyperactivity that was fully suppressed by MDL-100907. Interestingly, co-administration of MAOI harmaline (2-15 mg/kg) with a subthreshold dose of 5-MeO-DMT (2 mg/kg) induced excessive hyperactivities at late phase (45-180 min) 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.

KW - 5-HT receptor

KW - 5-MeO-DMT

KW - Activity

KW - Harmaline

KW - MAOI

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U2 - 10.1016/j.pharep.2016.01.008

DO - 10.1016/j.pharep.2016.01.008

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