title: 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.
abstract: 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.
authors.affiliation: Institute of Pharmacology, University of Ferrara, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ferraro
authors.forename: S
authors.initials: S
authors.lastname: Tanganelli
authors.forename: W T
authors.initials: WT
authors.lastname: O'Connor
authors.forename: T
authors.initials: T
authors.lastname: Antonelli
authors.forename: F
authors.initials: F
authors.lastname: Rambert
authors.forename: K
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D007034:Hypothalamus, Posterior / Q000378:metabolism*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D000077408:Modafinil; D011301:Preoptic Area / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology; D014326:Tropanes / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000493:pharmacokinetics*
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D012702:Serotonin Antagonists; D014326:Tropanes; D005680:gamma-Aminobutyric Acid; C042253:bemesetron; D000077408:Modafinil; D008784:Methysergide