Differential toxic effects of methamphetamine (METH) and methylenedioxymethamphetamine (MDMA) in multidrug-resistant (mdr1a) knockout mice
Brain Research September 1, 1997 Hema Mann, Bruce Ladenheim, Hiroshi Hirata et al. 50 citations
Methamphetamine (METH) and MDMA affect dopamine systems differently depending on the presence of P-glycoproteins, which regulate entry into the brain via the blood-brain barrier. In mice lacking the mdr1a gene (knockout), low doses of METH (2.5 mg/kg) caused marked decreases in dopamine and dopamine transporters in the striatum and nucleus accumbens, whereas wild-type mice showed only small changes. Higher METH doses produced similar effects in both strains. Conversely, MDMA caused greater percentage decreases in dopamine transporters in wild-type mice, with the lowest dose (5 mg/kg) significantly reducing transporters in the nucleus accumbens of wild-type but not knockout mice. These findings indicate that P-glycoproteins may facilitate MDMA entry into the brain but interfere with METH entry.