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Issue 1025 coverCurrent Status of Drug Dependence/Abuse Studies: Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity Volume 1025 published November 2004
Ann. N.Y. Acad. Sci. 1025: 181–188 (2004). doi: 10.1196/annals.1316.023
Copyright © 2004 by the New York Academy of Sciences
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Effects of Repeated Low Doses of MDMA on EEG Activity and Fluoro-Jade B Histochemistry

F FORNAIa,b, M GESIa, P LENZIa, M FERRUCCIa, G LAZZERIa, C PIZZANELLIa, A PELLEGRINIa, G BATTAGLIAb, S RUGGIERIb AND A PAPARELLIa

aDepartment of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy
bIstituto di Ricovero e Cura a Carattere Scientifco, Istituto Neuromed Mediterraneo, Neuromed Pozzilli (IS), Italy

Address for correspondence: Francesco Fornai, M.D., Department of Human Morphology and Applied Biology, University of Pisa, Via Roma, 55, 56126 Pisa, Italy. Voice: +39-050-2218611; fax: +39-050-2218606. f.fornai{at}med.unipi.it
Ann. N.Y. Acad. Sci. 1025: 181-188 (2004).

The psychostimulant 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is an amphetamine derivative that is widely abused. In previous studies, depending on the animal species, neurotoxicity has been demonstrated for either serotonin (5-HT) or/and dopamine (DA) nerve endings. These studies focused on the basal ganglia circuitry; however, in humans chronic abuse of MDMA often results in neurological symptoms that last after MDMA withdrawal and are not related to the extrapyramidal system such as electroencephalographic (EEG) abnormalities and cognitive impairment. These alterations might be due to the concomitant intake of other illicit compounds, the consequence of MDMA-induced hyperthermia, or to a primary neurotoxicity directed to extrastriatal regions. These observations call for a more in-depth analysis on the potential involvement of brain areas outside the basal ganglia in the toxic effects induced primarily by MDMA. In the present study, we treated C57Black mice chronically (25 days) with daily injections of MDMA (2.5 mg/kg). During treatments, mice were monitored in order to detect behavioral modifications, and epidural electrodes were installed to perform EEG recording. Behavioral data showed a sensitization as measured by locomotor activity, which related to progressive and long-lasting EEG changes and neuronal degeneration within the hippocampus.

Key Words: neurotoxicity • 3,4-methylenedioxymethamphetamine (MDMA) • ecstasy • limbic system • hippocampus • EEG






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