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-aminobutyric 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 [H-3]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.