Differential toxic effects of methamphetamine (METH) and methylenedioxymethamphetamine (MDMA) in multidrug-resistant (mdr1a) knockout mice
Hema Mann, Bruce Ladenheim, Hiroshi Hirata, Timothy H. Moran, Jean Lud Cadet
Brain Research September 1, 1997 DOI: 10.1016/s0006-8993(97)00754-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mdr1a wild-type and knockout mice |
| Interventions | Methamphetamine Methylenedioxymethamphetamine |
| Dose | 2.5, 5.0 and 10.0 mg/kg METH; 5.0, 10.0 and 20.0 mg/kg MDMA |
| Topics | MDMA |
| Keywords | Methamphetamine Meth- Nucleus accumbens Pharmacology Knockout mouse Striatum Dopaminergic |
| Citations | 50 |
| Key findings | METH and MDMA interact differentially with P-glycoproteins, which may facilitate MDMA entry into the brain but interfere with METH entry. |
Abstract
The toxic effects of methamphetamine (METH) (2.5, 5.0 and 10.0 mg/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/kg) caused only small changes in the wild-type, but marked. decreases in the mdr1a knockout mice. The two higher doses (5 mg/kg and 10 mg/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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 8
- Dopamine D2-receptor knockout mice are protected against dopaminergic neurotoxicity induced by methamphetamine or MDMA Neurobiology of Disease March 22, 2021
- A comparative study on the acute and long‐term effects of MDMA and 3,4‐dihydroxymethamphetamine (HHMA) on brain monoamine levels after i.p. or striatal administration in mice British Journal of Pharmacology 2005
- ( )-3,4-Methylenedioxymethamphetamine and Metabolite Disposition in Plasma and Striatum of Wild-Type and Multidrug Resistance Protein 1a Knock-Out Mice Journal of Analytical Toxicology September 1, 2011
- Of mice and men on MDMA: a translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy'). Brain Research November 14, 2019
- Mice in ecstasy: advanced animal models in the study of MDMA. Current Pharmaceutical Biotechnology August 1, 2010
and 3 more in the library
Cites 3
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- Superoxide radicals mediate the biochemical effects of methylenedioxymethamphetamine (MDMA): Evidence from using CuZn‐superoxide dismutase transgenic mice Synapse October 1, 1995
- Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain. Journal of Pharmacology and Experimental Therapeutics April 1, 1987