The antinarcoleptic drug modafinil increases glutamate release in thalamic areas and hippocampus.
The antinarcoleptic drug modafinil [(diphenyl-methyl)-sulfinyl-2-acetamide; Modiodal] dose-dependently inhibits the activity of GABA neurons in the cerebral cortex and in the nucleus accumbens, as well as in sleep-related brain areas such as the medial preoptic area and the posterior hypothalamus. This study examined the effects of modafinil (30-300 mg/kg, i.p.) on dialysate glutamate and GABA levels in the ventromedial (VMT) and ventrolateral (VLT) thalamus and hippocampal formation (Hip) of the awake rat. The results show a maximal increase in glutamate release in these brain regions at the 100 mg/kg dose, associated with a lack of effect on GABA release. Thus modafinil may increase excitatory glutamatergic transmission in these regions, altering the balance between glutamate and GABA transmission.
Ferraro
L
L
Department of Experimental and Clinical Medicine, University of Ferrara, Italy.
Antonelli
T
T
O'Connor
W T
WT
Tanganelli
S
S
Rambert
F
F
Fuxe
K
K
D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D000077408:Modafinil; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects; D013788:Thalamus / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000077408:Modafinil