4-Methylthioamphetamine increases dopamine in the rat striatum and has rewarding effects in vivo.
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.
Millennium Science Nucleus in Stress and Addiction and Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
Ramón
R
Sotomayor-Zárate
Gabriel
G
Quiroz
Katherine A
KA
Araya
Jorge
J
Abarca
María R
MR
Ibáñez
Alejandro
A
Montecinos
Carlos
C
Guajardo
Gabriel
G
Núñez
Angélica
A
Fierro
Pablo R
PR
Moya
Patricio
P
Iturriaga-Vásquez
Cristóbal
C
Gómez-Molina
Katia
K
Gysling
Miguel
M
Reyes-Parada
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000662:Amphetamines; D050483:Dopamine Plasma Membrane Transport Proteins; C078956:4-methylthioamphetamine; D004298:Dopamine