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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. Since 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 of 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.
| Authors: | Ramón Sotomayor‐Zárate, Gabriel Quiroz, Katherine A. Araya, Jorge Abarca, María R. Ibáñez, Alejandro Montecinos, Carlos Guajardo, Gabriel Núñez, Angelica Fierro, Pablo R. Moya, Patricio Iturriaga‐Vásquez, Cristóbal Gómez‐Molina, Katia Gysling, Miguel Reyes‐Parada | |
| Journal: | Basic & Clinical Pharmacology & Toxicology | |
| Year: | 2012 | |
| Pages: | n/a | |
| DOI: | 10.1111/j.1742-7843.2012.00926.x | |
| Publication date: | 12-07-2012 |
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