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, Ai-Ming Yu
Pharmacological Reports June 1, 2016 DOI: 10.1016/j.pharep.2016.01.008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | 5-MeO-DMT harmaline WAY-100635 MDL-100907 |
| Dose | 2, 10, 20 mg/kg 5-MeO-DMT; 2-15 mg/kg harmaline |
| Topics | 5-MeO-DMT DMT Serotonin |
| Keywords | 5-HT Receptor Harmaline Maoi 5-MEO-DMT Combination 5-MEO-DMT Synergy Compound interaction Drug combination Drug synergy Potentiation Hyperactivity: physical activity Motor activity Psychomotor stimulation Excessive movement Prolonged activity 5-ht1a 5-ht2a Receptor activation Neuropharmacology |
| Citations | 13 |
| Key findings | Co-administration of harmaline with a subthreshold dose of 5-MeO-DMT induces excessive late-phase hyperactivity that is abolished by blocking either 5-HT1A or 5-HT2A receptors. |
Abstract
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. 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. 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. 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.
Comparable studies
Other preclinical and animal studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Mice and rats | 2006 | Preclinical study | |
| Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Rats and transfected fibroblasts | 1998 | Experimental study | |
| Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat Intact rats and rats depleted of monoamines with reserpine | 1985 | Experimental study |
Citations in the library
Cited by 8
- The epidemiology of 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption. Journal of Psychopharmacology July 1, 2018
- A narrative synthesis of research with 5-MeO-DMT. Journal of Psychopharmacology March 1, 2022
- Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans Molecules April 22, 2021
- Behavioral Changes Over Time Following Ayahuasca Exposure in Zebrafish Frontiers in Behavioral Neuroscience July 28, 2017
- Inhaled 5-methoxy-N,N-dimethyltryptamine: Supportive context associated with positive acute and enduring effects Journal of Psychedelic Studies December 27, 2019
and 3 more in the library
Cites 29
- Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges. Pharmacology & Therapeutics May 1, 2004
- The hallucinogenic world of tryptamines: an updated review. Archives of Toxicology August 1, 2015
- Clinical toxicology of newer recreational drugs Clinical Toxicology October 1, 2011
- Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice Journal of Psychopharmacology December 8, 2010
- Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Current Drug Metabolism October 1, 2010
and 24 more in the library