Sleep disruption increases seizure susceptibility: Behavioral and EEG evaluation of an experimental model of sleep apnea Dragan Hrnčić a , Željko Grubač a , Aleksandra Rašić-Marković a , Nikola Šutulović a , Veselinka Šušić b , Jelica Bjekić-Macut c , Olivera Stanojlović a, ⁎ a Laboratory of Neurophysiology, Institute of Medical Physiology “Richard Burian”, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia b Serbian Academy of Sciences and Arts, 11000 Belgrade, Serbia c CHC Bežanijska Kosa, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia HIGHLIGHTS • We investigated the effects of sleep disruption on seizure susceptibility of rats. • We used experimental model of lindane-induced refractory seizures. • Sleep disruption frequency resembled that in patients with severe sleep apnea. • Sleep disruption potentiated both behavioral and EEG epileptic activity in rat. • This could explain the occurrence of epileptic symptoms in sleep apnea patients. abstract article info Article history: Received 11 June 2015 Received in revised form 14 December 2015 Accepted 15 December 2015 Available online 17 December 2015 Sleep disruption accompanies sleep apnea as one of its major symptoms. Obstructive sleep apnea is particularly common in patients with refractory epilepsy, but causing factors underlying this are far from being resolved. Therefore, translational studies regarding this issue are important. Our aim was to investigate the effects of sleep disruption on seizure susceptibility of rats using experimental model of lindane-induced refractory seizures. Sleep disruption in male Wistar rats with implanted EEG electrodes was achieved by treadmill method (belt speed set on 0.02 m/s for working and 0.00 m/s for stop mode, respectively). Animals were assigned to experi- mental conditions lasting 6 h: 1) sleep disruption (sleep interrupted, SI; 30 s working and 90 s stop mode every 2 min; 180 cycles in total); 2) activity control (AC, 10 min working and 30 min stop mode, 9 cycles in total); 3) treadmill chamber control (TC, only stop mode). Afterwards, the animals were intraperitoneally treated with lindane (L, 4 mg/kg, SI + L, AC + L and TC + L groups) or dimethylsulfoxide (DMSO, SIc, ACc and TCc groups). Convulsive behavior was assessed by seizure incidence, latency time to first seizure, and its severity dur- ing 30 min after drug administration. Number and duration of ictal periods were determined in recorded EEGs. Incidence and severity of lindane-induced seizures were significantly increased, latency time significantly de- creased in animals undergoing sleep disruption (SI + L group) compared with the animals from TC + L. Seizure latency was also significantly decreased in SI + L compared to AC + L groups. Number of ictal periods were in- creased and duration of it presented tendency to increase in SI + L comparing to AC + L. No convulsive signs were observed in TCc, ACc and SIc groups, as well as no ictal periods in EEG. These results indicate sleep disruption facilitates induction of epileptic activity in rodent model of lindane- epilepsy enabling translational research of this phenomenon. © 2015 Elsevier Inc. All rights reserved. Keywords: Sleep disruption Epilepsy Convulsive behavior EEG Rats 1. Introduction Sleep is a vital, natural, periodic and reversible physiological state of decreased vigilance. Therefore, changes in sleep duration and architec- ture are associated with different diseases, including cardiovascular dis- eases, neurological disorders, psychosis, bipolar disorder, as well as epilepsy [1]. Sleep deprivation has been identified as one of the leading Physiology & Behavior 155 (2016) 188–194 ⁎ Corresponding author at: Institute of Medical Physiology “Richard Burian”, Belgrade University Faculty of Medicine, Višegradska 26/II, 11000 Belgrade, Serbia. E-mail address: solja@afrodita.rcub.bg.ac.rs (O. Stanojlović). http://dx.doi.org/10.1016/j.physbeh.2015.12.016 0031-9384/© 2015 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Physiology & Behavior journal homepage: www.elsevier.com/locate/phb