Skip to main content
SpringerLink
Log in

Role of Melatonin Receptors in Hyperthermia-Induced Acute Seizure Model of Rats

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Melatonin is a neurohormone that has anticonvulsant activity in different experimental seizure models including hyperthermic febrile seizure. However, the mechanisms of this effect are not clear at the receptor level. The aim of the study was to determine which melatonin receptors involve in the hyperthermic febrile seizure model. 22–30 days Wistar male rats were used, and in children, it corresponds to 1.5–2 years. Groups were performed as (1) control, (2) ethanol/saline, (3) DMSO, (4) melatonin (MT), (5) MT + luzindole (LUZ), (6) MT + K-185, (7) MT + prazosin (PRZ), (8) MT + LUZ + K-185, (9) MT + LUZ + PRZ, (10) MT + K-185 + PRZ, and (11) MT + LUZ + PRZ + K-185. The hyperthermic febrile seizure pattern was established by keeping the rats in 45 °C hot water, and the latency, duration, and severity of seizures were determined in all groups. MT, LUZ, K-185, and PRZ were given 15, 45, 15, and 30 min before the induction of seizure, respectively. It was observed that melatonin shortened the duration of seizure, reduced the severity, and did not affect latency and that these effects were not completely blocked by receptor antagonists when compared with control, ethanol/saline, and DMSO groups. In conclusion, the fact that the anticonvulsant effect of melatonin is not completely blocked by all melatonin receptor antagonists. We can conclude that a multimodal mechanism may be responsible for the effect of melatonin receptors alone on the anticonvulsant effect of melatonin. It will be useful to design new pharmacological studies to make the subject clear.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Acuña Castroviejo D, Rosenstein RE, Romeo HE, Cardinali DP (1986) Changes in gamma-aminobutyric acid high affinity binding to cerebral cortex membranes after pinealectomy or melatonin administration to rats. Neuroendocrinology 43:24–31

    Article  Google Scholar 

  • Acuña-Castroviejo D, Escames G, Macías M, Muñóz Hoyos A, Molina Carballo A, Arauzo M, Montes R (1995) Cell protective role of melatonin in the brain. J Pineal Res 19:57–63

    Article  Google Scholar 

  • Arreola-Espino R, Urquiza-Marín H, Ambriz-Tututi M, Araiza-Saldaña CI, Caram-Salas NL, Rocha-González HI, Mixcoatl-Zecuatl T, Granados-Soto V (2007) Melatonin reduces formalin-induced nociception and tactile allodynia in diabeticrats. Eur J Pharmacol 577:203–210

    Article  CAS  Google Scholar 

  • Aydin L, Gundogan NU, Yazici C (2015) Anticonvulsant efficacy of melatonin in an experimental model of hyperthermic febrile seizures. Epilepsy Res 118:49–54

    Article  CAS  Google Scholar 

  • Aydin L, Yurtcu E, Korkmaz Y, Sezer T, Ogus E (2017) Effect of melatonin on cytokine levels in a hyperthermia-induced febrile seizure model. Cell Mol Biol (Noisy-le-grand) 63:11–16

    Article  Google Scholar 

  • Aygun H, Aydın D, Inanır S, Ekici F, Ayyıldız M, Agar A (2015) The effects of agomelatine and melatonin on ECoG activity of absence epilepsy model in WAG/Rij rats. Turk J Biol 39:904–910

    Article  CAS  Google Scholar 

  • Bikjdaouene L, Escames G, León J, Ferrer JM, Khaldy H, Vives F, Acuña-Castroviejo D (2003) Changes in brain amino acids and nitric oxide after melatonin administration in rats with pentylenetetrazole-induced seizures. J Pineal Res 35:54–60

    Article  CAS  Google Scholar 

  • Borowicz KK, Kamiñski R, G1sior 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

    Article  CAS  Google Scholar 

  • Cheng XP, Sun H, Ye ZY, Zhou JN (2012) Melatonin modulates the GABAergic response in cultured rat hippocampal neurons. J Pharmacol Sci 119:177–185

    Article  CAS  Google Scholar 

  • Costa-Lotufo LV, de Fonteles MM, Lim 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 131:521–529

    Google Scholar 

  • Dabak O, Altun D, Arslan M, Yaman H, Vurucu S, Yesilkaya E, Unay B (2016) Evaluation of plasma melatonin levels in children with afebrile and febrile Seizures. Pediatr Neurol 57:51–55

    Article  Google Scholar 

  • Dubé CM, Ravizza T, Hamamura M, Zha Q, Keebaugh A, Fok K, Andres AL, Nalcioglu O, Obenaus A, Vezzani A, Baram TZ (2010) Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers. J Neurosci 30:7484–7494

    Article  Google Scholar 

  • Fenoglio-Simeone K, Mazarati A, Sefidvash-Hockley S, Shin D, Wilke J, Milligan H, Sankar R, Rho JM, Maganti R (2009) Anticonvulsant effects of the selective melatonin receptor agonist ramelteon. Epilepsy Behav 16:52–57

    Article  Google Scholar 

  • Forcelli PA, Soper C, Duckles A, Gale K, Kondratyev A (2013) Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats. Epilepsy Res 107:217–223

    Article  CAS  Google Scholar 

  • Golombek DA, Fernández Duque D, De Brito Sánchez MG, Burin L, Cardinali DP (1992) Time-dependent anticonvulsant activity of melatonin in hamsters. Eur J Pharmacol 210:253–258

    Article  CAS  Google Scholar 

  • Inui Y, Hazeki O (2010) Acute effects of melatonin and its time of administration on core body temperature and heart rate in cynomolgus monkeys. J Toxicol Sci 35:383–391

    Article  CAS  Google Scholar 

  • Łotowska MES, Joanna M, Łotowska JM (2011) The neuroprotective effect of topiramate on the ultrastructure of pyramidal neurons of the hippocampal CA1 and CA3 sectors in an experimental model of febrile seizures in rats. Folia Neuropathol 49:230–236

    PubMed  Google Scholar 

  • Manev H, Uz T, Kharlamov A, Joo JY (1996) Increased brain damage after stroke or excitotoxic seizures in melatonin-deficient rats. FASEB J 10:1546–1551

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • Molina-Carballo A, Acuña-Castroviejo D, Rodriguez-Cabezas T, Muñoz-Hoyos A (1994) Effects of febrile and epileptic convulsions on daily variations in plasma melatonin concentration in children. J Pineal Res 16:1–9

    Article  CAS  Google Scholar 

  • Molina-Carballo A, Muñoz-Hoyos A, Sánchez-Forte M, Uberos-Fernández J, Moreno-Madrid F, Acuña-Castroviejo D (2007) Melatonin increases following convulsive seizures may be related to its anticonvulsant properties at physiological concentrations. Neuropediatrics 38:122–125

    Article  CAS  Google Scholar 

  • Mosińska P, Socała K, Nieoczym D, Laudon M, Storr M, Fichna J, Wlaź P (2016) Anticonvulsant activity of melatonin, but not melatonin receptor agonists Neu-P11 and Neu-P67, in mice. Behav Brain Res 307:199–207

    Article  Google Scholar 

  • Natsume J, Bernasconi N, Miyauchi M, Naiki M, Yokotsuka T, Sofue A, Bernasconi A (2007) Hippocampal volumes and diffusion-weighted image findings in children with prolonged febrile seizures. Acta Neurol Scand 115(Suppl 186):25–28

    Article  CAS  Google Scholar 

  • Niles LP, Smith LJ, Tenn CC (1997) Modulation of c-fos expression in the rat striatum by diazepam. Neurosci Lett 236:5–8

    Article  CAS  Google Scholar 

  • Peled N, Shorer Z, Peled E, Pillar G (2001) Melatonin effect on seizures in children with severe neurologic deficit disorders. Epilepsia 42:1208–1210

    Article  CAS  Google Scholar 

  • Ray M, Mediratta PK, Reeta K, Mahajan P, Sharma KK (2004) Receptor mechanisms involved in the anticonvulsant effect of melatonin in maximal electroshock seizures. Methods Find Exp Clin Pharmacol 26:177–181

    Article  CAS  Google Scholar 

  • Solmaz I, Gurkanlar D, Gokcil Z, Cuneyt G, Ozkan M, Erdogan E (2009) Antiepileptic activity of melatonin in Guinea pigs with pentylenetetrazol-induced seizures. Neurol Res 2009(31):989–985

    Article  Google Scholar 

  • Srinivasan V, Zakaria R, Jeet Singh H, Acuna-Castroviejo D (2012) Melatonin and its agonists in pain modulation and its clinical application. Arch Ital Biol 150:274–289

    PubMed  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Wellman P, Ho D, Cepeda-Benito A, Bellinger L, Nation J (2002) Cocaine-induced hypophagia and hyperlocomotion in rats are attenuated by prazosin. Eur J Pharmacol 455:117–126

    Article  CAS  Google Scholar 

  • Yahyavi-Firouz-Abadi N, Tahsili-Fahadan P, Riazi K, Ghahremani MH, Dehpour AR (2007) Melatonin enhances the anticonvulsant and proconvulsant effects of morphine in mice: role for nitric oxide signaling pathway. Epilepsy Res 75:138–144

    Article  CAS  Google Scholar 

  • Yamaguchi H, Nagase H, Ishida Y, Toyoshima D, Maruyama A, Tomioka K, Tanaka T, Nishiyama M, Fujita K, Mariko TI, Nozu K, Morioka I, Nishimura N, Kurosawa H, Takada S, Uetani Y, Iijima K (2018) Diurnal occurrence of complex febrile seizure and their severity in pediatric patients needing hospitalization. Epilepsy Behav 80:280–284

    Article  Google Scholar 

  • Yildirim M, Marangoz C (2006) Anticonvulsant effects of melatonin on penicillin-induced epileptiform activity in rats. Brain Res 1099:183–188

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by a grant from the Selcuk University, Scientific Research Council (grant number is 16401130). Authors would like to thank Begüm Aydin Gazi University Faculty of Medicine helps during experiments.

Author information

Authors and Affiliations

  1. Medical Faculty, Department of Physiology, Selcuk University, Konya, Turkey

    Rasim Mogulkoc & Abdülkerim Kasim Baltaci

  2. Department of Physiology, Meram Medical School, Necmettin Erbakan University, Konya, Turkey

    Leyla Aydin

Authors
  1. Rasim Mogulkoc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdülkerim Kasim Baltaci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leyla Aydin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rasim Mogulkoc.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mogulkoc, R., Baltaci, A.K. & Aydin, L. Role of Melatonin Receptors in Hyperthermia-Induced Acute Seizure Model of Rats. J Mol Neurosci 69, 636–642 (2019). https://doi.org/10.1007/s12031-019-01392-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-019-01392-y

Keywords

Search

Navigation