Modafinil and cortical gamma-aminobutyric acid outflow. Modulation by 5-hydroxytryptamine neurotoxins.
The acute or chronic administration of modafinil, (diphenyl-methyl-sulfinyl-2-acetamide, 30 mg/kg s.c.) decreased gamma-amino-butyric acid (GABA) outflow from the cerebral cortex of freely moving guinea pigs and rats. In 5,7-dihydroxytryptamine intracerebroventricularly pretreated guinea pigs, the effect of modafinil on GABA outflow was reversed and the noradrenaline cortical levels increased. Prazosin (35.8 ng/kg i.p.) blocked the drug-induced increase in GABA efflux. In vitro experiments, performed in rat cortical slices, showed that modafinil failed to affect [3H]GABA release and uptake as well as glutamic acid decarboxylase activity. In conclusion, our results suggest that the balance between central noradrenaline and 5-hydroxytryptamine transmission is important for the regulation by modafinil of the GABAergic release in the cerebral cortex.
Tanganelli
S
S
Department of Pharmacology, University of Ferrara, Italy.
Pérez de la Mora
M
M
Ferraro
L
L
Méndez-Franco
J
J
Beani
L
L
Rambert
F A
FA
Fuxe
K
K
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001559:Benzhydryl Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D000077408:Modafinil; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis / Q000378:metabolism*
D001559:Benzhydryl Compounds; D002395:Catecholamines; D000697:Central Nervous System Stimulants; D018756:GABA Antagonists; D009498:Neurotoxins; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; D000077408:Modafinil