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 Peer reviewed DOI: 10.1016/j.bbr.2018.07.020 via PubMed
Summary
5-Methoxy-α-methyltryptamine (5-MeO-AMT) induces a head-twitch response (HTR) in mice, indicating activation of serotonin receptor 2a. While acute administration led to HTR, tolerance developed with repeated doses. The antagonist ketanserin blocked this response. However, 5-MeO-AMT did not produce locomotor sensitization, conditioned place preference, or self-administration behaviors, suggesting it may have low potential for abuse.
Study at a glance
| Population | mice |
|---|---|
| Key finding | 5-MeO-AMT induces head-twitch response through serotonin receptor 2a activation but has low potential for abuse. |
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.