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 gamma-aminobutyric acid (GABA) r elease in the medial preoptic area (MPA) and posterior hypothalamus (P H) and the role of local 5-HT3 receptors in this effect was investigat ed in the awake rat using in vivo microdialysis. Modafinil (30-100 mg/ kg i.p.) dose-dependently decreased GABA release from the MPA, while o nly the 100 mg/kg dose markedly reduced GABA release in the PH. The mo dafinil (100 mg/kg) induced inhibition of GABA release in the MPA and the PH was partially counteracted by the 5-HT3 receptor antagonist MDL 72222 (1 mu M) when perfused locally alone or together with the non-se lective 5-HT receptor antagonist methysergide (1 mu M). Thus, the redu ction 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 vi gilance promoting action. Copyright (C) 1996 Elsevier Science Ireland Ltd.