CUZN SUPEROXIDE-DISMUTASE (CUZNSOD) TRANSGENIC MICE SHOW RESISTANCE TO THE LETHAL EFFECTS OF METHYLENEDIOXYAMPHETAMINE (MDA) AND OF METHYLENEDIOXYMETHAMPHETAMINE (MDMA)

We have used female and male transgenic (Tg) mice that carry the compl ete sequence of the human copper-zinc (CuZn) superoxide dismutase (SOD ) gene in order to assess the lethal effects of methylenedioxyamphetam ine (MDA) and methylenedioxymethamphetamine (MDMA). In contrast to non -Tg mice, both heterozygous and homozygous SOD-Tg mice showed resistan ce 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 r esistance to the effects of the two drugs. These results suggest that the acute lethal effects of amphetamine-substituted analogs might invo lve the intracellular overproduction of the superoxide radicals second ary to hypoxic injury. The gender differences suggest that there might be hormonal-free radical scavenger interactions that offer better pro tection to female mice. This might be related both to the lifespan of and to the lower prevalence of Parkinson's disease in women. Future st udies will need to address these issues further.