Modafinil enhances extracellular levels of dopamine in the nucleus accumbens and increases wakefulness in rats

Modafinil (MOD) is a wakefulness-promoting drug that improves the alertness levels in narcolepsy; however, the molecular mechanism of action remains to be elucidated. We found that after a single icy injection of MOD (10 mu g/5 mu l) the extracellular levels of dopamine (DA) and L-DOPA collected from the nucleus accumbens were increased and decreased, respectively. Separately, the icv administration of MOD (10 mu g/5 mu l) to rats enhanced wakefulness (W) whereas diminished sleep during 4 h. Lastly, the alertness induced by MOD was partially antagonized by the sleep-inducing endocannabinoid anandamide (ANA). We conclude that MOD enhances the extracellular levels of DA, promotes W and its effects on sleep are partially blocked by ANA. (c) 2006 Elsevier B.V. All rights reserved.