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

The effect of modafinil on endogenous γ-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 μM) when perfused locally alone or together with the non-selective 5-HT receptor antagonist methysergide (1 μM). 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.