Search

Background:Essential Tremor (ET) is a disease present in neurodegenerative disorders, such as Parkinson´s disease. Besides the motor dysfunction, ET also causes sleep problems, including excessive daytime sleepiness. To manage ET, several compounds are prescripted, such as primidone. However, no evidence is available regarding the effects of primidone on sleep. Objective: We analyzed the effects of systemic injections of primidone on sleep in rats. Method: Rats with sleep electrodes received different doses of primidone (0, 5, 10 or 50mg/Kg, i.p.) at the beginning of the lights-on period. Next, the effects of primidone on the states of vigilance were characterized.Results:At the highest dose of primidone (50mg/Kg), animals displayed an increase in Wakefulness (W) whereas Slow Wave Sleep (SWS) and Rapid Eye Movement Sleep (REMS) were decreased. In addition, sleep parameters such as the number of bouts, mean duration and latency were affected in primidone-treated animals. In this regard, the drug caused an enhancement in the number of bouts of W and SWS while the number of events of REMS showed a diminution. Regarding the mean duration, we found that SWS was decreased after primidone treatments whereas W and REMS remained with no statistical changes. Lastly, the latency of SWS was enhanced in primidone-treated animals while no statistical changes were found in REMS.Conclusion:Our findings demonstrate that primidone, a drug that is used to control ET, provokes wake-inducing effects 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 20 μg/1 μL) 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.

Regulation of the sleep-waking cycle is complex and involves diverse brain circuits and molecules. On one hand, an interplay among many neuroanatomical and neurochemical systems including acetylcholine, dopamine, noradrenaline, serotonin, histamine, and hypocretin has been shown to control the waking state. On the other hand the sleep-onset is governed by the activity of sleep-promoting neurons placed in the anterior hypothalamus that utilize GABA to inhibit wake-promoting regions. Moreover, brainstem regions inhibited during wakefulness (W) and slow wave sleeps (SWS) become active during rapid eye movement (REM) sleep. Further complexity has been introduced by the recognition of sleep-promoting molecules that accumulate in the brain in prolonged W as well as the physiological role of gene expression during sleep. The sleep-wake cycle is currently undergoing intense research with many new findings leading to new paradigms concerning sleep regulation, brain organization and sleep function. This review provides a broader understanding of our present knowledge in the field of sleep research.