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Perez de la Mora, M; Ferraro, L; Antonelli, T; Tanganelli, S; OConnor, WT; Mendez-Franco, J; Rambert, FA; Fuxe, K (1999)

THE VIGILANCE PROMOTING DRUG MODAFINIL INCREASES EXTRACELLULAR GLUTAMATE LEVELS IN THE MEDIAL PREOPTIC AREA AND THE POSTERIOR HYPOTHALAMUS OF THE CONS

NEUROPSYCHOPHARMACOL 20(4):346-356
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The effects of modafinil on glutamatergic and GABAergic transmission in the rat medial preoptic area (MPA) and posterior hypothalamus (PH), are analysed. Modafinil (30-300 mg/kg) increased glutamate and decreased GABA levels in the MPA and PH. Local perfusion with the GABA(A) agonist muscimol (10 mu M), reduced, while that GABA(A) antagonist bicuculline (1 mu M and 10 mu M) increased glutamate levels. The modafinil (100 mg/kg)-induced increase of glutamate levels was antagonized by local perfusion with bicuculline (1 mu M). When glutamate levels were increased by the local perfusion with the glutamate uptake inhibitor L-trans-PDC (0.5 mM), modafinil produced an additional enhancement of glutamate levels. Modafinil (1-33 mu M) failed to affect [H-3]glutamate uptake in hypothalamic synaptosomes and slices. These findings show that modafinil increases glutamate and decreases GABA levels in MPA and PH. The evidence that bicuculline counteracts that modafinil-induced increase of glutamate levels strengthens the evidence for an inhibitory GABA/glutamate interaction in the above regions controlling the sleep-wakefulness cycle. [Neuropsychopharmacology 20:346-356, 1999] (C) American College of Neuropsychopharmacology Published by Elsevier Science Inc.