In mice lacking the enzyme monoamine oxidase B (MAO-B), the neurotoxin DSP-4 caused the same loss of norepinephrine in brain regions as it did in normal mice, indicating MAO-B is not involved in DSP-4 toxicity. For the neurotoxin MDMA (ecstasy), MAO-B deficiency prevented the serotonin depletion normally seen in wild-type mice but led to a more pronounced dopamine loss. These results suggest MAO-B plays opposite roles in MDMA-induced damage to dopamine and serotonin systems.
MDMA treatment activates caspase-3, an enzyme involved in cell death, in the amygdala and hippocampus of rodents, but not in the striatum or frontal cortex. This indicates that limbic brain structures are particularly sensitive to MDMA's potential to trigger apoptotic pathways, which may help explain memory loss and cognitive impairments observed in chronic MDMA users.