THE EFFECTS OF MODAFINIL ON STRIATAL, PALLIDAL AND NIGRAL GABA AND GLUTAMATE RELEASE IN THE CONSCIOUS RAT - EVIDENCE FOR A PREFERENTIAL INHIBITION OF STRIATOPALLIDAL 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 (10 0 mg/kg) inhibited striatal (85 +/- 4% of basal values) and pallidal ( 85 +/- 2%) GABA release without influencing local glutamate release. A t 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. O n the contrary, in the substantia nigra modafinil reduced GABA release only at the 300 mg/kg dose (59 +/- 5%) without affecting glutamate re lease. 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 Elsev ier Science Ireland Ltd. All rights reserved.