Previous exposure to (+/-) 3,4-methylenedioxymethamphetamine produces long-lasting alteration in limbic brain excitability measured by electroencephalogram spectrum analysis, brain metabolism and seizure susceptibility
Giorgi FS, Pizzanelli C, Ferrucci M, Lazzeri G, Faetti M,
Giusiani M, Pontarelli F, Busceti CL, Murri L, Fornai F.
Department of Human Morphology and Applied Biology,
University of Pisa, Via Roma 55, 56126 Pisa, Italy;
Department of Neurosciences,
Section of Neurology,
University of Pisa, Pisa, Italy.
ABSTRACTSeizures 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/kgx2 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 [(14)C]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.Club drugs
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