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Variations in extracellular monoamines in the prefrontal cortex and medial hypothalamus after modafinil administration: a microdialysis study in rats

Hilaire, Zara de SaintCA; Orosco, Martine1; Rouch, Claude1; Blanc, Gérard2; Nicolaidis, Stylianos1

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The role of brain amines in mediating the effects of the wake-promoting agent modafinil, used in the treatment of sleepiness associated with narcolepsy is still uncertain. Therefore we studied the effects of modafinil on extracellular serotonin (5-HT), dopamine (DA) and noradrenaline (NA), in rat prefrontal cortex and in the medial hypothalamus area. Modafinil (128 mg/kg i.p.) significantly increased waking in the first 4 h of EEG sleep recording. This cortical and behavioral activation was associated with an initial increase in extracellular 5-HT, DA and NA during the first 60 min following modafinil administration. In the prefrontal cortex, 5-HT release remained high for 3 h after modafinil administration. In contrast, in the hypothalamus, only NA release was enhanced while DA and 5-HT levels remained low. In a first step, modafinil may generate waking partly via cortical monoamine release, particularly DA and 5-HT, and also hypothalamic NA. In a second step, maintenance of waking might depend on hypothalamic NA.

Division of Adult Psychiatry, Sleep Laboratory, University Hospital of Geneva (HUG), 2 Chemin du Petit Bel Air, CH-1225 Chêne-Bourg, Switzerland; 1CNRS ESA 7059 University Paris 7; 2INSERM U114, Chaire de Neuropharmacologie, Collège de France, Paris, France

CACorresponding Author

Received 1 August 2001; accepted 3 September 2001

© 2001 Lippincott Williams & Wilkins, Inc.