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The vigilance promoting drug modafinil
decreases GABA release in the medial preoptic area and in the posterior
hypothalamus of the awake rat: possible involvement of the serotonergic 5-HT3
receptor.
Ferraro L, Tanganelli S, O'Connor WT,
Antonelli T, Rambert F, Fuxe K.
Institute of Pharmacology,
University of Ferrara, Italy
Neurosci Lett 1996 Dec 6;220(1):5-8
Abstract:
The effect of modafinil on endogenous gamma-aminobutyric acid (GABA)
release in the medial preoptic area (MPA) and posterior hypothalamus (PH) and
the role of local 5-HT3 receptors in this effect was investigated in the awake
rat using in vivo microdialysis. Modafinil (30-100 mg/kg i.p.)
dose-dependently decreased GABA release from the MPA, while only the 100 mg/kg
dose markedly reduced GABA release in the PH. The modafinil (100 mg/kg)
induced inhibition of GABA release in the MPA and the PH was partially
counteracted by the 5-HT3 receptor antagonist MDL72222 (1 microM) when
perfused locally alone or together with the non-selective 5-HT receptor
antagonist methysergide (1 microM). Thus, the reduction of GABA transmission
induced by modafinil in the MPA and in the PH, at least in part, involves
local 5-HT3 receptors. The GABA release inhibition by modafinil in the above
areas may be relevant for its vigilance promoting action.
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