|
KMID : 0606920200280010083
|
|
Biomolecules & Therapeutics
2020 Volume.28 No. 1 p.83 ~ p.91
|
|
|
Four Novel Synthetic Tryptamine Analogs Induce Head-Twitch Responses and Increase 5-HTR2a in the Prefrontal Cortex in Mice
|
|
Abiero Arvie
Ryu In-Soo
Botanas Chrislean Jun
Custodio Raly James Perez
Sayson Leandro Val
Kim Mi-Kyung
Lee Hyun-Jun
Kim Hee-JIn
Seo Joung-Wook
Cho Min-Chang
Lee Kun-Won
Yoo Sung-Yeun
Jang Choon-Gon
Lee Yong-Sup
Cheong Jae-Hoon
|
|
|
Abstract
|
|
|
|
Tryptamines are monoamine alkaloids with hallucinogenic properties and are widely abused worldwide. To hasten the regulations of novel substances and predict their abuse potential, we designed and synthesized four novel synthetic tryptamine analogs: Pyrrolidino tryptamine hydrochloride (PYT HCl), Piperidino tryptamine hydrochloride (PIT HCl), N,N-dibutyl tryptamine hydrochloride (DBT HCl), and 2-Methyl tryptamine hydrochloride (2-MT HCl). Then, we evaluated their rewarding and reinforcing effects using the conditioned place preference (CPP) and self-administration (SA) paradigms. We conducted an open field test (OFT) to determine the effects of the novel compounds on locomotor activity. A head-twitch response (HTR) was also performed to characterize their hallucinogenic properties. Lastly, we examined the effects of the compounds on 5-HTR1a and 5-HTR2a in the prefrontal cortex using a quantitative real-time polymerase chain reaction (qRT-PCR) assay. None of the compounds induced CPP in mice or initiated SA in rats. PYT HCl and PIT HCl reduced the locomotor activity and elevated the 5-HTR1a mRNA levels in mice. Acute and repeated treatment with the novel tryptamines elicited HTR in mice. Furthermore, a drug challenge involving a 7-day abstinence from drug use produced higher HTR than acute and repeated treatments. Both the acute treatment and drug challenge increased the 5-HTR2a mRNA levels. Ketanserin blocked the induced HTR. Taken together, the findings suggest that PYT HCl, PIT HCl, DBT HCl, and 2-MT HCl produce hallucinogenic effects via 5-HTR2a stimulation, but may have low abuse potential.
|
|
|
KEYWORD
|
|
|
Novel synthetic tryptamine analogs, Abuse potential, Conditioned place preference, Self-administration, Head-twitch response, 5-HT2 receptors
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
  
|
|