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.
Department of Clinical and Experimental Medicine, University of Ferrara, Italy.
L
L
Ferraro
T
T
Antonelli
W T
WT
O'Connor
S
S
Tanganelli
F A
FA
Rambert
K
K
Fuxe
D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis / Q000379:methods; D000077408:Modafinil; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D014851:Wakefulness; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000502:physiology
D001559:Benzhydryl Compounds; D018756:GABA Antagonists; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000077408:Modafinil