Systemic Injections of Primidone Cause Wake-Inducing Effects in Rats

Author(s): Mireille Salas-Crisóstomo, María J. Franco-Tormo, Niurka Trujillo-Paredes, Gloria Arankowsky-Sandoval, Óscar Arias-Carrión, Sérgio Machado, Eric Murillo-Rodríguez*.

Journal Name: Current Psychopharmacology

Volume 8 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

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.

Keywords: Alertness, drug, essential tremor, Parkinson´s disease, stimulant, slow wave sleep.

[1]
Charles SK, Geiger DW, et al. Toward quantitative characterization of essential tremor for future tremor suppression. IEEE Int Conf Rehabil Robot 2017; 175-80.
[2]
Algarni M, Fasano A. The overlap between essential tremor and Parkinson disease. Parkinsonism Relat Disord 2018; 46(Suppl. 1): S101-4.
[3]
Louis ED. The evolving definition of essential tremor: What are we dealing with? Parkinsonism Relat Disord 2018; 46(Suppl. 1): S87-91.
[4]
Dyke JP, Cameron E, Hernandez N, Dydak U, Louis ED. Gray matter density loss in essential tremor: A lobule by lobule analysis of the cerebellum. Cerebellum Ataxias 2017; 4: 10.
[5]
Zesiewicz TA, Kuo SH. Essential tremor. BMJ Clin Evid 2015; 2015: 1206.
[6]
Barut BO, Tascilar N, Varo A. Sleep disturbances in essential tremor and Parkinson disease: A polysomnographic study. J Clin Sleep Med 2015; 11(6): 655-62.
[7]
Sengul Y, Sengul HS, Yucekaya SK, et al. Cognitive functions, fatigue, depression, anxiety, and sleep disturbances: assessment of nonmotor features in young patients with essential tremor. Acta Neurol Belg 2015; 115(3): 281-17.
[8]
Rohl B, Collins K, Morgan S, et al. Daytime sleepiness and nighttime sleep quality across the full spectrum of cognitive presentations in essential tremor. J Neurol Sci 2016; 371: 24-31.
[9]
Wasielewska A, Rudzińska M, Tomaszewski T, et al. Tremor in neuropathies of different origin. Neurol Neurochir Pol 2013; 47(6): 525-33.
[10]
Schmouth JF, Dion PA, Rouleau GA. Genetics of essential tremor: from phenotype to genes, insights from both human and mouse studies. Prog Neurobiol 2014; 119-20: 1-19.
[11]
Davidson AD, Charles SK. Fundamental principles of tremor propagation in the upper limb. Ann Biomed Eng 2017; 45(4): 1133-47.
[12]
Wharen RE Jr, Okun MS, Guthrie BL, et al. Thalamic DBS with a constant-current device in essential tremor: A controlled clinical trial. Parkinsonism Relat Disord 2017; 40: 18-26.
[13]
Fenoy AJ, Schiess MC. Deep brain stimulation of the dentato-rubro-thalamic tract: Outcomes of direct targeting for tremor. Neuromodulation 2017; 20(5): 429-36.
[14]
Elias WJ, Lipsman N, Ondo WG, et al. A randomized trial of focused ultrasound thalamotomy for essential tremor. N Engl J Med 2016; 375(8): 730-9.
[15]
Schreglmann SR, Bauer R, Hägele-Link S, et al. Unilateral cerebellothalamic tract ablation in essential tremor by MRI-guided focused ultrasound. Neurol 2017; 88(14): 1329-33.
[16]
Ye Y, Liao S, Luo B, Ni L. Botulinum toxin treatment for essential palatal tremors presenting with nasal clicks instead of pulsatile tinnitus: a case report. Head Face Med 2016; 12(1): 33.
[17]
Bruno E, Nicoletti A, Quattrocchi G, et al. Pregabalin for essential tremor. Cochrane Database Syst Rev 2016; 10: CD009682.
[18]
Bruno E, Nicoletti A, Fillipini G, et al. Zonisamide for essential tremor. Cochrane Database Syst Rev 2017; 8: CD009684.
[19]
Ondo W. Essential Tremor: What we can learn from current pharmacotherapy. Tremor Other Hyperkinet Mov 2016; 6: 356.
[20]
Wisden W, Yu X, Franks NP. GABA receptors and the pharmacology of sleep. Handb Exp Pharmacol 2017. In Press.
[21]
Murillo-Rodríguez E, Di Marzo V, Machado S. Rocha, et al. Role of N-Arachidonoyl-Serotonin (AA-5-HT) in sleep-wake cycle architecture, sleep homeostasis, and neurotransmitters regulation. Front Mol Neurosci 2017; 30(10): 152.
[22]
Mijangos-Moreno S, Poot-Ake A, Guzmán K, et al. Sleep and neurochemical modulation by the nuclear peroxisome proliferator-activated receptor alpha (PPAR-alpha) in rat. Neurosci Res 2016; 105: 65-9.
[23]
Gironell A. The GABA hypothesis in essential tremor: Lights and shadows. Tremor Other Hyperkinet Mov (N Y) 2014; 4: 254.
[24]
DeWoskin D, Myung J, Belle MD, Piggins HD, Takumi T, Forger DB. Distinct roles for GABA across multiple timescales in mammalian circadian timekeeping. Proc Natl Acad Sci USA 2015; 112(29): E3911-9.
[25]
Krügel U, Straub I, Beckmann H, Schaefer M. Primidone inhibits TRPM3 and attenuates thermal nociception in vivo. Pain 2017; 158(5): 856-67.
[26]
Cull-Candy S, Kelly L, Farrant M. Regulation of Ca2+-permeable AMPA receptors: Synaptic plasticity and beyond. Curr Opin Neurobiol 2006; 16(3): 288-97.
[27]
Gees M, Colsoul B, Nilius B. The role of transient receptor potential cation channels in Ca2+ signaling. Cold Spring Harb Perspect Biol 2010; 2(10): a003962.
[28]
Léna I, Parrot S, Deschaux O, et al. Variations in extracellular levels of dopamine, noradrenaline, glutamate, and aspartate across the sleep-wake cycle in the medial prefrontal cortex and nucleus accumbens of freely moving rats. J Neurosci Res 2005; 81(6): 891-9.
[29]
Lau CG, Takeuchi K, Rodenas-Ruano A, et al. Regulation of NMDA receptor Ca2+ signalling and synaptic plasticity. Biochem Soc Trans 2009; 37(Pt 6): 1369-74.
[30]
Lin JS, Anaclet C, Sergeeva OA, Haas HL. The waking brain: An update. Cell Mol Life Sci 2011; 68(15): 2499-512.
[31]
Shepherd JD. Memory, plasticity and sleep - A role for calcium permeable AMPA receptors? Front Mol Neurosci 2012; 5: 49.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 8
ISSUE: 1
Year: 2019
Page: [72 - 78]
Pages: 7
DOI: 10.2174/2211556007666180425143506
Price: $58

Article Metrics

PDF: 50
HTML: 2