Differential enhancement of dialysate serotonin levels in distinct brain regions of the awake rat by modafinil: possible relevance for wakefulness and depression.

The present in vivo microdialysis study evaluates the possible existence of a differential regulation of serotonergic transmission by the antinarcoleptic drug modafinil [(diphenyl-methyl)-sulfinyl-2-acetamide; Modiodal] among various brain regions of the awake rat. The results show that, in the cerebral cortex, the central amygdala, and the dorsal raphe nucleus, modafinil in the dose range of 10-100 mg/kg i.p. dose-dependently increases dialysate serotonin (5-HT) levels. In other brain areas, such as the medial preoptic area and the posterior hypothalamus, the modafinil-induced increase in dialysate 5-HT levels is observed only at tenfold higher doses (100 mg/kg), 10-30 mg/kg being ineffective. Together these data suggest that, in the frontal cortex, the amygdala, and the dorsal raphe, modafinil is more potent in enhancing extracellular 5-HT levels and presumably 5-HT transmission than in the medial preoptic area and the posterior hypothalamus. In view of the role of ascending 5-HT pathways in arousal and depression, it seems likely that the antinarcoleptic drug modafinil may also have an antidepressant potential in addition to its wakefulness-promoting action, both actions involving enhancement of 5-HT neurotransmission. Copyright 2002 Wiley-Liss, Inc.