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Mann H, Ladenheim B, Hirata H, Moran TH, Cadet JL.
“Differential toxic effects of methamphetamine (METH) and methylenedioxymethamphetamine (MDMA) in multidrug-resistant (mdr1a) knockout mice”.
Brain Res. 1997 Sep 26;769(2):340-6.
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Abstract
The toxic effects of methamphetamine METH 2.5, 5.0 and 10.0 mg r kg and methylenedioxymethamphetamine MDMA 5.0, 10.0 and 20.0 mg / kg on dopaminergic systems were assessed in the striatum and of the nucleus accumbens in mdr1a wild-type and knockout
mice. METH caused significant dose-dependent decreases of dopamine DA and DA transporters DAT in the striatum and the nucleus
accumbens NAc of both wild-type and knockout mice. The lowest doses of METH 2.5 mg r kg caused only small changes in the wild-type, but marked decreases in the mdr1a knockout mice. The two higher doses 5 mg r kg and 10 mg r kg caused similar changes in both strains of mice. In contrast to METH, MDMA caused greater percentage decreases in DAT in the wild-type mice. For example, the lowest dose 5 mg / kg caused significant decreases in DAT in the NAc of wild-type but not of mdr1a knockout mice. The highest dose 20 mg / kg caused similar changes in both the strains. These results suggest that METH and MDMA interact differentially with P-glycoproteins. These observations document, for the first time, a role for these proteins in the entry of METH and MDMA into the brain via the blood–brain barrier, with P-glycoprotein possibly facilitating the entry of MDMA but interfering with that of METH into the brain.
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