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

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Autor Sotomayor-Zarate R.
Autor Quiroz G.
Autor Araya K.A.
Autor Abarca J.
Autor Ibanez M.R.
Autor Montecinos A.
Autor Guajardo C.
Autor Nunez G.
Autor Fierro A.
Autor Moya P.R.
Autor Iturriaga-Vasquez P.
Autor Gomez-Molina C.
Autor Gysling K.
Autor Reyes-Parada M.
Fecha Ingreso 2014-04-05T00:18:44Z
Fecha Disponible 2014-04-05T00:18:44Z
Fecha en Repositorio 2014-04-04
dc.identifier 10.1111/j.1742-7843.2012.00926.x
dc.description.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. © 2012 Nordic Pharmacological Society. en_US
dc.source Basic and Clinical Pharmacology and Toxicology
Link Descarga dc.source.uri
Title dc.title 4-Methylthioamphetamine Increases Dopamine in the Rat Striatum and has Rewarding Effects In Vivo en_US
Tipo dc.type Article
dc.description.keywords 4 methylthioamphetamine; amphetamine derivative; dopamine; dopamine transporter; protein c fos; unclassified drug; animal experiment; animal tissue; article; controlled study; corpus striatum; dopamine brain level; dose response; drug protein binding; extracellular space; in vitro study; in vivo study; locomotion; male; molecular docking; nonhuman; nucleus accumbens; place preference; priority journal; radioassay; rat; reward; structural homology; Amphetamines; Animals; Chromatography, High Pressure Liquid; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Male; Motor Activity; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Rattus en_US

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