Intrahypothalamic administration of modafinil increases expression of MAP-kinase in hypothalamus and pons in rats

Modafinil (MOD) it has to be considered as a wake-inducing drug to treat sleep disorders such as excessive sleepiness in narcolepsy, shift-work disorder, and obstructive/sleep apnea syndrome. Current evidence suggests that MOD induces waking involving the dopamine D₁ receptor. However, little is known regarding the molecular elements linked in the wake-promoting actions of MOD. Since the D₁ receptor activates the mitogen-activated protein kinase (MAP-K) cascade, it raises the interesting possibility that effects of MOD would depend upon the activation of MAP-K. Here we tested the expression of MAP-K in hypothalamus as well as pons after the microinjection of MOD (10 or 20μg/1μL) in rats into anterior hypothalamus, a wake-inducing brain area. Intrahypothalamic injections of MOD promoted MAP-K phosphorylation in hypothalamus and pons. Taken together, these results suggest that the wake-inducing compound MOD promotes the MAP-K phosphorylation.