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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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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.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA

    Xi-Ling Jiang & Hong-Wu Shen

  2. Department of Biochemistry & Molecular Medicine, UC Davis School of Medicine, Sacramento, CA, USA

    Ai-Ming Yu

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  1. Xi-Ling Jiang
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Correspondence to Ai-Ming Yu.

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Jiang, XL., Shen, HW. & Yu, AM. Modification of 5-methoxy-N, N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms. Pharmacol. Rep 68, 608–615 (2016). https://doi.org/10.1016/j.pharep.2016.01.008

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  • DOI: https://doi.org/10.1016/j.pharep.2016.01.008

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