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Modafinil prevents glutamate cytotoxicity in cultured cortical neurons

Antonelli, Tiziana1; Ferraro, Luca1; Hillion, Joelle2; Tomasini, Maria Cristina1; Rambert, Francis A.3; Fuxe, Kjell1,4


THE ability of modafinil (Modiodal®) to protect cortical neurons from glutamate-induced degeneration was evaluated by measuring electrically evoked [3H]GABA release and [3H]GABA uptake in primary cerebral cortical cultures In normal cells, electrical stimulation (10 Hz, 2 min) increased [3H]GABA release (FR-NER St1 = 0.77 ± 0.14; St2/St1 ratio = 0.94 ± 0.02). The exposure of sister cells to glutamate, reduced electrically evoked [3H]GABA release (FR-NER St1 = 0.40 ± 0.05; St2/St1 ratio = 0.60 ± 0.08). Modafinil (0.3–1 μM) prevented the glutamate-induced reduction of the St2/St1 ratio (0.85 ± 0.11; 0.88 ± 0.05, respectively). A similar protective effect was observed for [3H]GABA uptake. These findings suggest that modafinil may be neuroprotective in that it attenuates glutamate-induced excitotoxicity in cortical neurons

1Department of Experimental and Clinical Medicine, Pharmacology Section, University of Ferrara, Ferrara, Italy

2Department of Neuroscience, Division of Cellular and Molecular Neurochemistry, Karolinska Institutet, S-171 77, Stockholm, Sweden

3Neuropsychopharmacologie, Centre de Recherches, Laboratoire L. Lafon, Maisons-Alfort, France

4Corresponding Author: Kjell Fuxe

ACKNOWLEDGEMENTS: This work has been supported by grants from Laboratoire L. Lafon, Maisons-Alfort, France and Italian MURST (60%).

Received 9 September 1998; accepted 9 October 1998

© 1998 Lippincott Williams & Wilkins, Inc.