The effects of modafinil on striatal, pallidal and nigral GABA and glutamate release in the conscious rat: evidence for a preferential inhibition of striato-pallidal GABA transmission

The effects of the anti-narcoleptic drug modafinil (30-300 mg/kg i.p.) on GABA and glutamate release were evaluated in the basal ganglia of the conscious rat, by using the microdialysis technique. Modafinil (100 mg/kg) inhibited striatal (85 +/- 4% of basal values) and pallidal (85 +/- 2%) GABA release without influencing local glutamate release. At the highest dose (300 mg/kg), modafinil induced a further reduction of pallidal (75 +/- 2%) but not striatal (82 +/- 7%) GABA release and increased striatal (134 +/- 11%) but not pallidal glutamate release. On the contrary, in the substantia nigra modafinil reduced GABA release only at the 300 mg/kg dose (59 +/- 5%) without affecting glutamate release. The preferential reduction in striato-pallidal GABA release at the 100 mg/kg dose of modafinil suggests that modafinil may be useful in the treatment of Parkinsonian diseases. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved.