5-Methoxy-α-methyltryptamine (5-MeO-AMT), a tryptamine derivative, induces head-twitch responses in mice through the activation of serotonin receptor 2a in the prefrontal cortex.
Arvie Abiero, Chrislean Jun Botanas, Leandro Val Sayson, Raly James Custodio, June Bryan De la Peña, Mikyung Kim, Hyun Jun Lee, Joung-Wook Seo, In Soo Ryu, Cho Min Chang, Ji Seul Yang, Yong Sup Lee, Choon-Gon Jang, Hee Jin Kim, Jae Hoon Cheong
Behavioural Brain Research February 1, 2019 DOI: 10.1016/j.bbr.2018.07.020 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | 5-MeO-AMT |
| Dose | 0.3, 1, 3, 10 mg/kg |
| Duration | 7 days |
| Topics | 5-MeO-DMT Serotonin |
| Keywords | 5-methoxy-a-methyltryptamine Conditioned place preference Head-twitch response Self-administration Serotonin receptor 2a |
| Citations | 17 |
| Key findings | 5-MeO-AMT induces head-twitch response via 5-HTR2a activation in the prefrontal cortex and shows low abuse potential. |
Abstract
5-Methoxy-α-methyltryptamine (5-MeO-AMT) is a tryptamine derivative that is used recreationally because of its reported hallucinogenic and mood elevating effects. Studies suggest that the psychopharmacological effects of tryptamines involve serotonin receptor 2a (5-HTR2a) activation in the brain. The head-twitch response (HTR) is widely used as a behavioral correlate for assessing 5-HTR2a agonist activity of a drug. Thus, we investigated whether 5-MeO-AMT induces HTR in mice and explored its mechanism of action. 5-MeO-AMT (0.3, 1, 3, 10 mg/kg) was administered once a day for 7 days, and the HTR was measured after 1 day (acute) and 7 days (repeated) of administration. Another cohort of mice was treated with 5-HTR2a antagonist ketanserin (KS) before 5-MeO-AMT administration. We measured 5-HTR2a and 5-HTR2c mRNA levels in the prefrontal cortex of the mice treated acutely or repeatedly with 5-MeO-AMT. We performed western blotting to determine the effects of the drug on the expression of G protein (Gq/11), protein kinase C gamma (PKC-γ), and extracellular signal-regulated kinases 1/2 (ERK1/2), in addition to PKC-γ and ERK1/2 phosphorylation. Additionally, we evaluated potential rewarding and reinforcing effects of 5-MeO-AMT using locomotor sensitization, conditioned place preference (CPP), and self-administration (SA) paradigms. Acute 5-MeO-AMT administration elicited the HTR, while repeated administration resulted in tolerance. KS blocked the 5-MeO-AMT-induced HTR. 5-MeO-AMT increased 5-HTR2a mRNA levels and induced PKC-γ phosphorylation in the prefrontal cortex. 5-MeO-AMT did not induce locomotor sensitization, CPP, or SA. This study shows that 5-MeO-AMT induces HTR through 5-HTR2a activation in the prefrontal cortex, and may have low potential for abuse.
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 13
- Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology May 1, 2020
- NBOMes–Highly Potent and Toxic Alternatives of LSD Frontiers in Neuroscience February 26, 2020
- Two newly-emerging substituted phenethylamines MAL and BOD induce differential psychopharmacological effects in rodents Journal of Psychopharmacology July 10, 2020
- Understanding ayahuasca effects in major depressive disorder treatment through in vitro metabolomics and bioinformatics. Analytical and Bioanalytical Chemistry July 1, 2023
- Serotonin 2C receptors are also important in head-twitch responses in male mice. Psychopharmacology July 1, 2025
and 8 more in the library
Cites 25
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology May 20, 2016
- Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex Journal of Neuroscience October 1, 2003
- Clinical toxicology of newer recreational drugs Clinical Toxicology October 1, 2011
- The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. European Journal of Pharmacology March 22, 2007
and 20 more in the library