6-hydroxy-dopamine treatment counteracts the reduction of cortical GABA release produced by the vigilance promoting drug modafinil in the awake freely moving guinea-pig.

The effects of acute and repeated treatments with modafinil (30 mg/kg, s.c.) alone or after i.c.v. 6-hydroxy-dopamine injection were studied on cortical GABA release as well as on cortical/striatal catecholamine levels in awake freely moving guinea pig. The results show that repeated daily modafinil treatment produces a similar but short-lasting reduction of GABA outflow compared with acute administration. A significant reduction of cortical basal GABA outflow was observed in animals treated with 6-hydroxy-dopamine, which was maintained also after modafinil treatments. Furthermore, after the 6-hydroxy-dopamine treatment, modafinil fails to inhibit cortical GABA release. The depleting action of the toxin, 17% reduction of neostriatal dopamine levels and 35% of noradrenaline levels in the parietal cortex, was not influenced by repeated modafinil treatment. The catecholaminergic telencephalic networks therefore seem essential for the elicitation of the inhibitory effects of modafinil on GABA release.