Abiero, ArvieBotanas, Chrislean JunSayson, Leandro ValCustodio, Raly Jamesde la Peña, June BryanKim, MikyungLee, Hyun JunSeo, Joung-WookRyu, In SooChang, Cho MinYang, Ji SeulLee, Yong SupJang, Choon-GonKim, Hee JinCheong, Jae Hoon2020-09-162020-09-162018-07-240166-4328https://dx.doi.org/10.1016/j.bbr.2018.07.020https://hdl.handle.net/10735.1/8898Due 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).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 (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.en©2018 Elsevier B.V. All rights reserved.5-methoxy-α-methyltryptamineHallucinogenic drugsPsilocybinReceptor, Serotonin, 5-HT2ASelf AdministrationSerotonin 5-HT2 Receptor AgonistsarticleAbiero, 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.2018.07.020359