Provigil is an increasingly popular wake-promoting drug used for the treatment of narcolepsy, but its precise mechanism of action is unknown. To determine potential pathways via which Provigil acts, we administered a range of doses of Provigil to rats, recorded sleep/wake activity, and studied the pattern of neuronal activation using Fos immunohistochemistry.
To contrast Provigil-induced wakefulness with spontaneous wakefulness, we administered Provigil at midnight, during the normal waking period of rats. To determine the influence of circadian phase or ambient light, we also injected Provigil at noon on a normal light/dark cycle or in constant darkness. We found that 75 mg/kg Provigil increased Fos immunoreactivity in the tuberomammillary nucleus (TMN) and in orexin (hypocretin) neurons of the perifornical area, two cell groups implicated in the regulation of wakefulness. This low dose of Provigil also increased the number of Fos-immunoreactive (Fos-IR) neurons in the lateral subdivision of the central nucleus of the amygdala.