TY - JOUR
T1 - 4-Methylthioamphetamine Increases Dopamine in the Rat Striatum and has Rewarding Effects In Vivo
AU - Sotomayor-Zárate, Ramón
AU - Quiroz, Gabriel
AU - Araya, Katherine A.
AU - Abarca, Jorge
AU - Ibáñez, María R.
AU - Montecinos, Alejandro
AU - Guajardo, Carlos
AU - Núñez, Gabriel
AU - Fierro, Angélica
AU - Moya, Pablo R.
AU - Iturriaga-Vásquez, Patricio
AU - Gómez-Molina, Cristóbal
AU - Gysling, Katia
AU - Reyes-Parada, Miguel
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84869202147&partnerID=8YFLogxK
U2 - 10.1111/j.1742-7843.2012.00926.x
DO - 10.1111/j.1742-7843.2012.00926.x
M3 - Article
C2 - 22788961
AN - SCOPUS:84869202147
SN - 1742-7835
VL - 111
SP - 371
EP - 379
JO - Basic and Clinical Pharmacology and Toxicology
JF - Basic and Clinical Pharmacology and Toxicology
IS - 6
ER -