The antinarcoleptic drug modafinil increases glutamate release in thalamic areas and hippocampus

Neuroreport. 1997 Sep 8;8(13):2883-7. doi: 10.1097/00001756-199709080-00016.


The antinarcoleptic drug modafinil [(diphenyl-methyl)-sulfinyl-2-acetamide; Modiodal] dose-dependently inhibits the activity of GABA neurons in the cerebral cortex and in the nucleus accumbens, as well as in sleep-related brain areas such as the medial preoptic area and the posterior hypothalamus. This study examined the effects of modafinil (30-300 mg/kg, i.p.) on dialysate glutamate and GABA levels in the ventromedial (VMT) and ventrolateral (VLT) thalamus and hippocampal formation (Hip) of the awake rat. The results show a maximal increase in glutamate release in these brain regions at the 100 mg/kg dose, associated with a lack of effect on GABA release. Thus modafinil may increase excitatory glutamatergic transmission in these regions, altering the balance between glutamate and GABA transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / pharmacology*
  • Central Nervous System Stimulants / pharmacology*
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / metabolism*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Male
  • Microdialysis
  • Modafinil
  • Rats
  • Rats, Sprague-Dawley
  • Sleep / drug effects
  • Thalamus / drug effects*
  • Thalamus / metabolism
  • gamma-Aminobutyric Acid / metabolism*


  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • Excitatory Amino Acid Antagonists
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Modafinil