The effects of agomelatine and melatonin on ECoG activity of absenceepilepsy model in WAG/Rij rats

The aim of this study was to evaluate the effect of the melatonergic M1 and M2 receptor agonist and serotonergic 5-HT2C receptor antagonist agomelatine on the spike wave discharges (SWDs) seen in electrocorticographic (ECoG) recordings of WAG/Rij rats with absence epilepsy. Twenty-one WAG/Rij male rats were used in this study. Tripolar electrodes were placed on skulls and control ECoG activities were recorded. Experimental groups received normal saline (Group I: 1 mL, intraperitoneally (i.p)), agomelatine (Group II: 40 mg/kg, i.p), and melatonin (Group III: 40 mg/kg, i.p) injections for 7 days. Following this period, 2-h ECoG recordings were repeated. The number of SWDs and their durations were calculated. The total number and duration of SWDs decreased in both the agomelatine and melatonin groups. The systemic administration of agomelatine and melatonin attenuated the genetic absence epilepsy seizures in WAG/Rij rats. The repressive effect of agomelatine on the absence seizures was similar to that of the melatonin used in this study.

The effects of agomelatine and melatonin on ECoG activity of absenceepilepsy model in WAG/Rij rats

The aim of this study was to evaluate the effect of the melatonergic M1 and M2 receptor agonist and serotonergic 5-HT2C receptor antagonist agomelatine on the spike wave discharges (SWDs) seen in electrocorticographic (ECoG) recordings of WAG/Rij rats with absence epilepsy. Twenty-one WAG/Rij male rats were used in this study. Tripolar electrodes were placed on skulls and control ECoG activities were recorded. Experimental groups received normal saline (Group I: 1 mL, intraperitoneally (i.p)), agomelatine (Group II: 40 mg/kg, i.p), and melatonin (Group III: 40 mg/kg, i.p) injections for 7 days. Following this period, 2-h ECoG recordings were repeated. The number of SWDs and their durations were calculated. The total number and duration of SWDs decreased in both the agomelatine and melatonin groups. The systemic administration of agomelatine and melatonin attenuated the genetic absence epilepsy seizures in WAG/Rij rats. The repressive effect of agomelatine on the absence seizures was similar to that of the melatonin used in this study.

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  • Agar E (2015). The role of cannabinoids and leptin in neurological diseases. Acta Neurol Scand (in press).
  • Aguiar CC, Almeida AB, Araujo PV, Vasconcelos GS, Chaves EM, do Vale OC, Macedo DS, de Sousa FC, Viana GS, Vasconcelos SM (2012). Anticonvulsant effects of agomelatine in mice. Epilepsy Behav 24: 324–328.
  • Antón-Tay F (1974). Melatonin: effects on brain function. Adv Biochem Psychopharmacol 11: 315–324.
  • Arslan G, Alici SK, Ayyildiz M, Agar E (2013). The role of CB1- receptors in the proconvulsant effect of leptin on penicillininduced epileptiform activity in rats. CNS Neurosci Ther 19: 222–228.
  • Arslan G, Ayyildiz M, Agar E (2014). The interaction between ghrelin and cannabinoid systems in penicillin-induced epileptiform activity in rats. Neuropeptides 48: 345–352.
  • Aydın D, Yıldırım M, Ayyıldız M, Ağar E (2013). The effect of combined treatment of alpha-tocopherol, ascorbic acid and pyridoxine with NMDA blocker, memantine on penicillin induced epileptiform activity in rats. Turk J Med Sci 43: 245– 250.
  • Banach M, Gurdziel E, Jedrych M, Borowicz KK (2011). Melatonin in experimental seizures and epilepsy. Pharmacol Rep 63: 1–11.
  • Barylnik JB, Filippova NV, Trayber LV( 2014). Modern approaches to the synchronization of  circadian rhythms  in treatment of depression. Zh Nevrol Psikhiatr Im S S Korsakova 114: 124– 128.
  • Bazil CW (2003). Epilepsy and sleep disturbance. Epilepsy Behav 4: 39–45.
  • Bazil CW, Short D, Crispin D, Zheng W (2000). Patients with intractable epilepsy have low  melatonin, which increases following seizures. Neurology 55: 1746–1748.
  • Beck-Friis J (1985). Serum melatonin in relation to clinical variables in patients with major depressive disorder and a hypothesis of a low melatonin syndrome. Acta Psychiatr Scand 71: 319–330.
  • Bodinat CD, Lemaitre GB, Mocaer E, Renard P, Muñoz C, Millan MJ (2010). Agomelatine, the first melatonergic antidepressant: discovery, characterization and development. Nat Rev Drug Discov 9: 628–642.
  • Borowicz KK, Kaminski R, Gasior M, Kleinrok Z, Czuczwar SJ (1999). Influence of melatonin upon the protective action of conventional anti-epileptic drugs against maximal electroshock in mice. Eur Neuropsychopharmacol 9: 185–190.
  • Cakil D, Yildirim M, Ayyildiz M, Agar E (2011). The effect of coadministration of the NMDA blocker with agonist and antagonist of CB1-receptor on penicillin-induced epileptiform activity in rats. Epilepsy Res 93: 128–133.
  • Champney TH, Hanneman WH, Legare ME, Appel K (1996). Acute and chronic effects of melatonin as an anticonvulsant in male gerbils. J Pineal Res 20: 79–83.
  • Coenen AM, van Luijtelaar EL (1987). The WAG/Rij rat model for absence epilepsy: age and sex factors. Epilepsy Res 1: 297–301.
  • Costa-Lotufo LV, Fonteles MMF, Lima ISP, de Oliveira AA, Nascimento VS, de Bruin VM, Viana GS (2002). Attenuating effects of melatonin on pilocarpine-induced seizures in rats. Comp Biochem Physiol C Toxicol Pharmacol 131: 521–529.
  • Dailey JW, Naritoku DK (1996). Antidepressants and seizures: clinical anecdotes overshadow neuroscience. Biochem Pharmacol 52: 1323–1329.
  • D’Amore V, Santolini I, van Rijn CM, Biagioni F, Molinaro G, Prete A, Conn PJ, Lindsley CW, Zhou Y, Vinson PN  et al. (2013).
  • Potentiation of mGlu5 receptors with the novel enhancer, VU0360172, reduces spontaneous absence seizures inWAG/ Rij rats. Neuropharmacology 66: 330–338.
  • Dastgheib M, Moezi L (2014). Acute and chronic effects of  agomelatine  on intravenous penthylenetetrazol-induced seizure in mice and the probable role of nitric oxide. Eur J Pharmacol 736: 10–15.
  • Delagrange P, Boutin JA (2006). Therapeutic potential of melatonin ligands. Chronobiol Int 23: 413–418.
  • Demir Özkay Ü, Söztutar E, Can ÖD, Üçel Uİ, Öztürk Y, Ulupinar E (2015). Effects of long-term agomelatine treatment on the cognitive performance and hippocampal plasticity of adult rats. Behav Pharmacol 26: 469–480.
  • Demyttenaere K (2011). Agomelatine: a narrative review. Eur Neuropsychopharmacol 4: S703–S709.
  • Drinkenburg WH, Coenen AM, Vossen JM, van Luijtelaar E L (2001). Spike-wave discharges and sleep-wake states in rats with absence epilepsy. Epilepsy Res 2: 218–224.
  • Floreani M, Skaper SD, Facci L, Lipartiti M, Giusti P (1997). Melatonin  maintains glutathione homeostasis in kainic acidexposed rat brain tissues. FASEB J 11: 1309–1315.
  • Fuchs E, Simon M, Schmelting B (2006). Pharmacology of a new antidepressant: benefit of the implication of the melatonergic system. Int Clin Psychopharmacol 1: S17–S20.
  • Gupta M, Gupta YK, Agarwal S, Aneja S, Kalaivani M, Kohli K (2004). Effects of add-on melatonin administration on  antioxidant enzymes  in children with  epilepsy  taking carbamazepine monotherapy: a randomized,  double-blind, placebo-controlled trial. Epilepsia 45: 1636–1639.
  • Kovacs Z,  Kekesi KA,  Dobolyi A, Lakatos R, Juhasz G (2015). Absence epileptic activity changing effects of non-adenosine nucleoside inosine, guanosine and uridine in Wistar Albino Glaxo Rijswijk rats. Neuroscience 6: 593–608.
  • Kozan R, Ayyildiz M, Yildirim M, Agar E (2006). The effects of ethanol intake and withdrawal on penicillin-induced epileptiform activity in rats. Brain Res Bull 71: 111–115.
  • Leproult R, Van Onderbergen A, L’hermite-Baleriaux M, Van Cauter E, Copinschi G (2005). Phaseshifts of  24-h  rhythms  of hormonal release and  body temperature  following early evening administration of the melatonin agonist agomelatine in healthy older men. Clin Endocrinol 63: 298–304.
  • Lima E, Cabral FR, Cavalheiro EA, Naffah-Mazzacoratti MG, Amado D (2011). Melatonin administration after pilocarpine-induced status epilepticus: a new way to prevent or attenuate postlesion epilepsy? Epilepsy Behav 20: 607–612.
  • Manning JP, Richards DA, Bowery NG (2003). Pharmacology of absence epilepsy. Trends Pharmacol Sci 24: 542–549.
  • Moezi L, Shafaroodi H, Hojati A, Dehpour AR (2011). The interaction of melatonin and agmatine on pentylenetetrazole-induced seizure threshold in mice. Epilepsy Behav 22: 200–206.
  • Mula M, Schmitz B (2009). Depression in epilepsy: mechanisms and therapeutic approach. Ther Adv Neurol Dis 2: 337–344.
  • Munoz Hoyos A, Molina Carballo A, Macias M, Rodriguez Cabezas T, Martin Medina E, Narbona Lopez E, Valenzuela Ruiz A, Acuna Castroviejo D (1998). Comparison between tryptophan methoxyindole and kynurenine metabolic pathways in normal and preterm neonates and in neonates with acute fetal distress. Eur J Endocrinol 139: 89–95.
  • Musshoff U, Speckmann EJ (2003). Diurnal actions of melatonin on epileptic activity in hippocampal slices of rats. Life Sci 73: 2603–2610.
  • Nazıroğlu M, Yüksel M, Köse SA, Özkaya MO (2013). Recent reports of Wi-Fi and mobile phone-induced radiation on oxidative stress and reproductive signaling pathways in females and males. J Membr Biol 246: 869–875.
  • Ngomba RT,  Santolini I,  Biagioni F,  Molinaro G,  Simonyi A,  van Rijn CM,  D’Amore V,  Mastroiacovo F,  Olivieri G,  Gradini R  et al. (2011). Protective role for type-1 metabotropic  glutamate  receptors against spike and wave discharges in the  WAG/Rij rat  model of absence epilepsy. Neuropharmacology 60: 1281–1291.
  • Noe KH, Locke DEC, Sirven JI (2011). Treatment of depression in patients with epilepsy. Curr Treat Option N 13: 371–379. Paxinos G, Watson C (1998). The Rat Brain in Stereotaxic Coordinates. 4th ed. New York, NY, USA: Academic Press.
  • Reiter RJ, Tan DX, Manchester LC, Pilar Terron M, Flores LJ, Koppisepi S (2007). Medical implications of melatonin: receptor-mediated and receptor-independent actions. Adv Med Sci 52: 11–28.
  • Robillard R,  Naismith SL,  Rogers NL,  Scott EM,  Ip TK,  Hermens DF,  Hickie IB (2013). Sleep-wake cycle and  melatonin  rhythms  in adolescents and young adults with mood  disorders: comparison of unipolar and bipolar phenotypes. Eur Psychiatry 28: 412–416.
  • Rubin RT, Heist EK, McGeoy SS, Hanada K, Lesser IM (1992). Neuroendocrine aspects of primary endogenous depression. XI. Serum melatonin measures in patients and matched control subjects. Arch Gen Psychiatry 49: 558–567.
  • Sandyk R, Tsagas N, Anninos PA (1992). Melatonin as a proconvulsive hormone in humans. Int J Neurosci 63: 125–135.
  • Sarkisova KY, Kuznetsova GD, Kulikov MA, van Luijtelaar G (2010). Spike-wave discharges are necessary for the expression of behavioral depression-like symptoms. Epilepsia 51: 146–160.
  • Sarkisova K, van Luijtelaar G (2011). The WAG/Rij strain: a genetic animal model of absence epilepsy with comorbidity of depression. Prog Neuropsychopharmacol Biol Psychiatry 35: 854–876.
  • Srivastava AK, Gupta SK, Jain S, Gupta YK (2002). Effect of melatonin and phenytoin on an intracortical ferric chloride model of posttraumatic seizures in rats. Methods Find Exp Clin Pharmacol 24: 145–149.
  • Steriade M, McCormick DA, Sejnowski J (1993). Thalamocortical oscillations in the sleeping and aroused brain. Science 262: 679–685.
  • Stewart LS, Leung LS (2005). Hippocampal melatonin receptors modulate seizure threshold. Epilepsia 46: 473–480.
  • Sweis D (2005). The uses of melatonin. Arch Dis Child Educ Pract Ed 90: 74–77.
  • Tchekalarova J, Petkova Z, Pechlivanova D, Moyanova S, Kortenska L, Mitreva R, Lozanov V, Atanasova D, Lazarov N, Stoynev A (2013). Prophylactic treatment with melatonin after status epilepticus: effects on epileptogenesis, neuronal damage and behavioral changes in kainate model of temporal lobe epilepsy. Epilepsy Behav 27: 174–187.
  • Tolmacheva EA, van Luijtelaar G (2007). Absence seizures are reduced by the enhancement of GABA-ergic inhibition in the hippocampus in WAG/Rij rats. Neurosci Lett 416: 17–21.
  • Trinka E, Kienpointner G, Unterberger I, Luef G, Bauer G, Doering LB, Doering S (2006). Psychiatric comorbidity in juvenile myoclonic epilepsy. Epilepsia 47: 2086–2091.
  • Yalyn O, Arman F, Erdogan F, Kula M (2006). A comparison of the circadian rhythms and the levels of melatonin in patients with diurnal and nocturnal complex partial seizures. Epilepsy Behav 8: 542–546.
  • Yehuda S, Mostofsky DI (1993). Circadian effects of beta-endorphin, melatonin, DSIP, and amphetamine on pentylenetetrazoleinduced seizures. Peptides 14: 203–205.
  • Yildirim M, Aydin-Abidin S, Abidin I, Akca M, Canpolat S, Cansu A (2013). Evaluation of the role of chronic daily melatonin administration and pinealectomy on penicillin-induced focal epileptiform activity and spectral analysis of ECoG in rats: an in vivo electrophysiological study. Neurochem Res 38: 1672– 1685.
  • Yildirim M, Marangoz C (2006). Anticonvulsant effects of melatonin on penicillin-induced epileptiform activity in rats. Brain Res 1099: 183–188.
  • Yürüker V, Nazıroğlu M, Şenol N (2015). Reduction in traumatic brain injury-induced oxidative stress, apoptosis, and calcium entry in rat hippocampus by melatonin: possible involvement of TRPM2 channels. Metab Brain Dis 30: 223–231.
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