Variations in extracellular monoamines in the prefrontal cortex and medial hypothalamus after modafinil administration: a microdialysis study in rats.
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.
de Saint Hilaire
Z
Z
Division of Adult Psychiatry, Sleep Laboratory, University Hospital of Geneva (HUG), 2 Chemin du Petit Bel Air, CH-1225 Chêne-Bourg, Switzerland.
Orosco
M
M
Rouch
C
C
Blanc
G
G
Nicolaidis
S
S
D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D015306:Biogenic Monoamines / Q000096:biosynthesis*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism; D007033:Hypothalamus, Middle / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis / Q000379:methods; D000077408:Modafinil; D009638:Norepinephrine / Q000096:biosynthesis / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000096:biosynthesis / Q000378:metabolism
D001559:Benzhydryl Compounds; D015306:Biogenic Monoamines; D000697:Central Nervous System Stimulants; D012701:Serotonin; D000077408:Modafinil; D004298:Dopamine; D009638:Norepinephrine