4-Methylthioamphetamine Increases Dopamine in the Rat Striatum and has Rewarding Effects In Vivo

Ramón Sotomayor-Zárate, Gabriel Quiroz, Katherine A. Araya, Jorge Abarca, María R. Ibáñez, Alejandro Montecinos, Carlos Guajardo, Gabriel Núñez, Angélica Fierro, Pablo R. Moya, Patricio Iturriaga-Vásquez, Cristóbal Gómez-Molina, Katia Gysling, Miguel Reyes-Parada*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

4-Methylthioamphetamine (MTA) is a phenylisopropylamine derivative whose use has been associated with severe intoxications. MTA is usually regarded as a selective serotonin-releasing agent. Nevertheless, previous data have suggested that its mechanism of action probably involves a catecholaminergic component. As little is known about dopaminergic effects of this drug, in this work the actions of MTA upon the dopamine (DA) transporter (DAT) were studied in vitro, in vivo and in silico. Also, the possible abuse liability of MTA was behaviourally assessed. MTA exhibited an in vitro affinity for the rat DAT in the low micromolar range (6.01 μM) and induced a significant, dose-dependent increase in striatal DA. MTA significantly increased c-Fos-positive cells in striatum and nucleus accumbens, induced conditioned place preference and increased locomotor activity. Docking experiments were performed in a homology model of the DAT. In conclusion, our results show that MTA is able to increase extracellular striatal DA levels and that its administration has rewarding properties. These effects were observed at concentrations or doses that can be relevant to its use in human beings.

Original languageEnglish
Pages (from-to)371-379
Number of pages9
JournalBasic and Clinical Pharmacology and Toxicology
Volume111
Issue number6
DOIs
StatePublished - Dec 2012
Externally publishedYes

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