A microdialysis and behavioural investigation of modafinil in freely moving rats

Modafinil (Provigil®) is an unusual stimulant that is widely used to treat narcolepsy in USA and Europe. It has an enigmatic mechanism of action (see reviews by Minzenberg & Carter, 2008; Heal et al, 2012). Modafinil has stimulant-like effects in humans and animals, but its pharmacology is different from the catecholaminergic stimulants d-amfetamine and methylphenidate. Although modafinil has low micromolar affinity for DAT (Zolkowska et al., 2009; Madras et al., 2006) and no affinity for NET or SERT (Madras et al, 2006; Minzenberg & Carter, 2008), positron emission tomography (PET) experiments have paradoxically revealed that therapeutic doses of modafinil occupy a substantial proportion of striatal DAT sites in the brains of humans (Volkow et al, 2009). Modafinil also decreased [11C]raclopride binding (Volkow et al, 2009), indicating occupancy of DAT sites resulted in increased synaptic concentrations of dopamine.