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CuZn-superoxide dismutase (CuZnSOD) transgenic mice show resistance to the lethal effects of methylenedioxyamphetamine (MDA) and of methylenedioxymethamphetamine (MDMA).

J L Cadet, Bruce Ladenheim, I Baum, Elaine Carlson, Charles B. Epstein

Brain Research August 1, 1994 DOI: 10.1016/0006-8993(94)91624-1 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Animal experiment Peer reviewed
Population Female and male transgenic and non-transgenic mice
Interventions Methylenedioxyamphetamine (MDA) Methylenedioxymethamphetamine (MDMA)
Topics MDMA
Keywords Animals Mice, transgenic Humans Superoxides N-methyl-3,4-methylenedioxyamphetamine Superoxide dismutase Injections, intraperitoneal Oxygen consumption Sex characteristics Female
Key findings Transgenic mice carrying the human CuZn superoxide dismutase gene, especially homozygotes, were more resistant to the lethal effects of MDA and MDMA than non-transgenic mice, and females were somewhat more resistant than males. The authors suggest these acute lethal effects may involve intracellular superoxide overproduction secondary to hypoxic injury, with hormonal-free radical scavenger interactions possibly offering females better protection.

Abstract

We have used female and male transgenic (Tg) mice that carry the complete sequence of the human copper-zinc (CuZn) superoxide dismutase (SOD) gene in order to assess the lethal effects of methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA). In contrast to non-Tg mice, both heterozygous and homozygous SOD-Tg mice showed resistance to the lethal effects of both drugs. Females of both SOD-Tg and non-Tg strains were somewhat more resistant to the effects of these drugs in comparison to males. In general, homozygous animals show greater resistance to the effects of the two drugs. These results suggest that the acute lethal effects of amphetamine-substituted analogs might involve the intracellular overproduction of the superoxide radicals secondary to hypoxic injury. The gender differences suggest that there might be hormonal-free radical scavenger interactions that offer better protection to female mice. This might be related both to the lifespan of and to the lower prevalence of Parkinson's disease in women. Future studies will need to address these issues further.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study Year Design Participants
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats 1998 Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA 1999 Observational cohort

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