The unfinished journey with modafinil and discovery of a novel population of modafinil-immunoreactive neurons.

Modafinil, a wake-promoting compound now used worldwide in sleep medicine, was initially regarded as a sedative compound because mice were so quiet with respect to locomotion after receiving it that this behavioral state was qualified as sedation. In the early 1980's when modafinil was first assessed by polysomnography in a cat in our laboratory, surprisingly, the cat spent the whole night awake without even one minute of sleep! This initial observation resulted subsequently in a series of basic and clinical studies in order to define the pharmacological profile of modafinil and its mode of action and, notably, to identify the brain targets by which modafinil acts to promote wakefulness. These studies were undertaken using pharmacologic approach coupled with the Cerveau isolé (brain transection) preparation, c-fos labelling and knockout mouse models.