The vigilance promoting drug modafinil decreases GABA release in the medial preoptic area and in the posterior hypothalamus of the awake rat: possible involvement of the serotonergic 5-HT3 receptor

Neurosci Lett. 1996 Dec 6;220(1):5-8. doi: 10.1016/s0304-3940(96)13212-2.


The effect of modafinil on endogenous gamma-aminobutyric acid (GABA) release in the medial preoptic area (MPA) and posterior hypothalamus (PH) and the role of local 5-HT3 receptors in this effect was investigated in the awake rat using in vivo microdialysis. Modafinil (30-100 mg/kg i.p.) dose-dependently decreased GABA release from the MPA, while only the 100 mg/kg dose markedly reduced GABA release in the PH. The modafinil (100 mg/kg) induced inhibition of GABA release in the MPA and the PH was partially counteracted by the 5-HT3 receptor antagonist MDL72222 (1 microM) when perfused locally alone or together with the non-selective 5-HT receptor antagonist methysergide (1 microM). Thus, the reduction of GABA transmission induced by modafinil in the MPA and in the PH, at least in part, involves local 5-HT3 receptors. The GABA release inhibition by modafinil in the above areas may be relevant for its vigilance promoting action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arousal / drug effects*
  • Benzhydryl Compounds / pharmacology*
  • Central Nervous System Stimulants / pharmacology*
  • Hypothalamus, Posterior / metabolism*
  • Male
  • Methysergide / pharmacology
  • Modafinil
  • Preoptic Area / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Antagonists / pharmacology
  • Tropanes / pharmacology
  • gamma-Aminobutyric Acid / pharmacokinetics*


  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • Serotonin Antagonists
  • Tropanes
  • gamma-Aminobutyric Acid
  • bemesetron
  • Modafinil
  • Methysergide