Previous exposure to (±) 3,4-methylenedioxymethamphetamine produces long-lasting alteration in limbic brain excitability measured by electroencephalogram spectrum analysis, brain metabolism and seizure susceptibility

Seizures represent the most common neurological emergency in ecstasy abusers; however, no study addressed whether (±) 3,4- methylenedioxymethamphetamine ("ecstasy") per se might produce long-lasting alterations in brain excitability related to a pro-convulsant effect. C57Black mice were treated with three regimens of (±) 3,4-methylenedioxymethamphetamine (5mg/kg×2 for 1, 2 or three consecutive days). Following the last dose of (±) 3,4-methylenedioxymethamphetamine, during a time interval of 8 weeks, the following procedures were carried out: 1) cortical electroencephalographic recordings, including power-spectrum analysis; 2) administration of sub-threshold doses of kainate; 3) measurement of regional [¹⁴C]2-deoxyglucose uptake; 4) monoamine assay. We demonstrate that all mice pre-treated with (±) 3,4-methylenedioxymethamphetamine showed long-lasting encephalographic changes with frequencies peaking at 3-4.5Hz at the power-spectrum analysis. This is concomitant with latent brain hyperexcitability within selected limbic brain regions, as shown by seizure facilitation and long-lasting latent metabolic hyperactivity which can be unraveled by phasic glutamate stimulation. This study sheds new light into the brain targets of (±) 3,4-methylenedioxymethamphetamine and discloses the occurrence of (±) 3,4-methylenedioxymethamphetamine-induced latent hyperexcitability within limbic areas, while it might provide a model to study in controlled experimental conditions limbic seizures and status epilepticus in C57Black mice. Persistent changes produced by (±) 3,4- methylenedioxymethamphetamine in limbic brain excitability might be responsible for seizures and limbic-related disorders in chronic (±) 3,4-methylenedioxymethamphetamine abusers.