title: Previous exposure to (+/-) 3,4-methylenedioxymethamphetamine produces long-lasting alteration in limbic brain excitability measured by electroencephalogram spectrum analysis, brain metabolism and seizure susceptibility.
abstract: 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. C57 Black mice were treated with three regimens of (+/-) 3,4-methylenedioxymethamphetamine (5mg/kg x 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 [(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 3-4.5 Hz 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 C57 Black 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.
authors.affiliation: Department of Human Morphology and Applied Biology, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
authors.forename: F S
authors.initials: FS
authors.lastname: Giorgi
authors.forename: C
authors.initials: C
authors.lastname: Pizzanelli
authors.forename: M
authors.initials: M
authors.lastname: Ferrucci
authors.forename: G
authors.initials: G
authors.lastname: Lazzeri
authors.forename: M
authors.initials: M
authors.lastname: Faetti
authors.forename: M
authors.initials: M
authors.lastname: Giusiani
authors.forename: F
authors.initials: F
authors.lastname: Pontarelli
authors.forename: C L
authors.initials: CL
authors.lastname: Busceti
authors.forename: L
authors.initials: L
authors.lastname: Murri
authors.forename: F
authors.initials: F
authors.lastname: Fornai
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D004198:Disease Susceptibility; D004569:Electroencephalography; D005947:Glucose / Q000378:metabolism; D007608:Kainic Acid; D008032:Limbic System / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D015306:Biogenic Monoamines; D005947:Glucose; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D007608:Kainic Acid