Neuropharmacology and Neurotoxicity of 3,4-Methylenedioxymethamphetamine - Drugs of Abuse: Neurological Reviews and Protocols - page 62

Fig. 2. Treatment of rats and recordings are the same as described in the legend for
Fig. 1. The duration of time spent in wakefulness, slow-wave sleep (SWS), and REM
sleep (REM) is plotted as a percentage of values obtained prior to drug treatment.
MDMA may induce long-term alterations in behavior that are unrelated to the
long-term depletion of brain 5-HT.
Treatment of adult or neonatal rats with MDMA also results in impairments
in learning and memory, and these effects also may be unrelated to long-term
defi cits in brain 5-HT. In adult rats, MDMA treatment results in defi cits in
object recognition (96) . The administration of MDMA on postnatal d 11-20
results in defi cits in tests of sequential learning and spatial learning and memory
when rats are tested as adults, and these defi cits are evident in the absence of
signifi cant depletions in brain 5-HT (99) .
8. Summary
The existing data indicate that MDMA produces long-term deficits in
markers of 5-HT axon terminals in the rodent brain. Increased cleavage of
the cytoskeletal protein tau, impairment of axonal transport, and functional
consequences associated with a 5-HT depleting regimen of MDMA support the
view that MDMA induces structural brain damage, that is, axonal degeneration.
A confl uence of oxidative stress and bioenergetic stress induced by MDMA
is hypothesized to underlie the process of MDMA neurotoxicity ( Fig. 3 ). The
actions of MDMA on the 5-HT transporter to promote free radical formation
and/or intracellular calcium may synergize with MDMA-induced disturbances
in cellular energetics and hyperthermia to effect selective toxicity to 5-HT
axon terminals.