The vigilance promoting drug modafinil increases extracellular glutamate levels in the medial preoptic area and the posterior hypothalamus of the conscious rat: Prevention by local GABA(A) receptor blockade
L. Ferraro et al., The vigilance promoting drug modafinil increases extracellular glutamate levels in the medial preoptic area and the posterior hypothalamus of the conscious rat: Prevention by local GABA(A) receptor blockade, NEUROPSYCH, 20(4), 1999, pp. 346-356
The effects of modafinil on glutamatergic and GABAergic transmission in the
rat medial preoptic area (MPA) and posterior hypothalamus (PH), are analys
ed. Modafinil (30-300 mg/kg) increased glutamate and decreased GABA levels
in the MPA and PH. Local perfusion with the GABA(A) agonist muscimol (10 mu
M), reduced, while that GABA(A) antagonist bicuculline (1 mu M and 10 mu M
) increased glutamate levels. The modafinil (100 mg/kg)-induced increase of
glutamate levels was antagonized by local perfusion with bicuculline (1 mu
M). When glutamate levels were increased by the local perfusion with the g
lutamate uptake inhibitor L-trans-PDC (0.5 mM), modafinil produced an addit
ional enhancement of glutamate levels. Modafinil (1-33 mu M) failed to affe
ct [H-3]glutamate uptake in hypothalamic synaptosomes and slices. These fin
dings show that modafinil increases glutamate and decreases GABA levels in
MPA and PH. The evidence that bicuculline counteracts that modafinil-induce
d increase of glutamate levels strengthens the evidence for an inhibitory G
ABA/glutamate interaction in the above regions controlling the sleep-wakefu
lness cycle. [Neuropsychopharmacology 20:346-356, 1999] (C) American Colleg
e of Neuropsychopharmacology Published by Elsevier Science Inc.