Systemic Injections of Primidone Cause Wake-Inducing Effects in Rats

Abstract

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. 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. Our findings demonstrate that primidone, a drug that is used to control ET, provokes wake-inducing effects in rats.