The amphetamine analog MDA, which has hallucinogenic effects, causes long-lasting reductions in serotonin levels, serotonin uptake sites, and a serotonin metabolite in rat brains. Morphological evidence suggests these changes result from degeneration of serotonin nerve terminals. These findings indicate MDA is toxic to serotonin neurons in rats and raise concerns about whether MDA and similar hallucinogenic amphetamines could cause serotonin neurotoxicity in humans.
Small changes in ambient temperature alter core body temperature in rats given MDMA, and those temperature shifts influence the drug's neurotoxicity. Rats treated with MDMA at 20 or 22°C showed a drop in core temperature and no detectable damage to serotonin nerve endings in brain regions examined. At 26–30°C, core temperature rose and neurotoxicity appeared in the frontal cortex, somatosensory cortex, hippocampus, and striatum, with damage severity linked to core temperature. Saline-treated rats showed no temperature changes across the same ambient conditions. These findings suggest ambient temperature strongly affects MDMA's toxicity and thermoregulation, with implications for human use where fatal hyperthermia occurs.