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

Neuroreport. 2001 Nov 16;12(16):3533-7. doi: 10.1097/00001756-200111160-00032.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / administration & dosage*
  • Biogenic Monoamines / biosynthesis*
  • Central Nervous System Stimulants / administration & dosage*
  • Dopamine / biosynthesis
  • Dopamine / metabolism
  • Extracellular Space / drug effects*
  • Extracellular Space / metabolism
  • Hypothalamus, Middle / drug effects*
  • Hypothalamus, Middle / metabolism
  • Injections, Intraperitoneal
  • Male
  • Microdialysis* / methods
  • Modafinil
  • Norepinephrine / biosynthesis
  • Norepinephrine / metabolism
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism
  • Rats
  • Rats, Wistar
  • Serotonin / biosynthesis
  • Serotonin / metabolism


  • Benzhydryl Compounds
  • Biogenic Monoamines
  • Central Nervous System Stimulants
  • Serotonin
  • Modafinil
  • Dopamine
  • Norepinephrine