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

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dc.contributor.authorAbiero, Arvie
dc.contributor.authorBotanas, Chrislean Jun
dc.contributor.authorSayson, Leandro Val
dc.contributor.authorCustodio, Raly James
dc.contributor.authorde la Peña, June Bryan
dc.contributor.authorKim, Mikyung
dc.contributor.authorLee, Hyun Jun
dc.contributor.authorSeo, Joung-Wook
dc.contributor.authorRyu, In Soo
dc.contributor.authorChang, Cho Min
dc.contributor.authorYang, Ji Seul
dc.contributor.authorLee, Yong Sup
dc.contributor.authorJang, Choon-Gon
dc.contributor.authorKim, Hee Jin
dc.contributor.authorCheong, Jae Hoon
dc.contributor.utdAuthorde la Peña, June Bryan
dc.date.accessioned2020-09-16T19:44:04Z
dc.date.available2020-09-16T19:44:04Z
dc.date.issued2018-07-24
dc.descriptionDue to copyright restrictions and/or publisher's policy full text access from Treasures at UT Dallas is limited to current UTD affiliates (use the provided Link to Article).
dc.description.abstract5-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 (G_{q/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.
dc.description.departmentSchool of Natural Sciences and Mathematics
dc.description.sponsorshipMinistry of Food and Drug Safety (MFDS) of Korea (14182MFDS979) and the National Research Foundation of Korea (NRF-2017R1D1A1A02018695)
dc.identifier.bibliographicCitationAbiero, Arvie, Chrislean Jun Botanas, Leandro Val Sayson, Raly James Custodio, et al. 2019. "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." Behavioural Brain Research 359: 828-835, doi: 10.1016/j.bbr.2018.07.020
dc.identifier.issn0166-4328
dc.identifier.urihttps://dx.doi.org/10.1016/j.bbr.2018.07.020
dc.identifier.urihttps://hdl.handle.net/10735.1/8898
dc.identifier.volume359
dc.language.isoen
dc.publisherElsevier Science Bv
dc.rights©2018 Elsevier B.V. All rights reserved.
dc.source.journalBehavioural Brain Research
dc.subject5-methoxy-α-methyltryptamine
dc.subjectHallucinogenic drugs
dc.subjectPsilocybin
dc.subject.meshReceptor, Serotonin, 5-HT2A
dc.subject.meshSelf Administration
dc.subject.meshSerotonin 5-HT2 Receptor Agonists
dc.title5-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
dc.type.genrearticle

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