Investigation of anti-epileptic mechanisms of 5HT1A receptor with pentylenetetrazole induced epilepsy model in rats

Bilal Şahin; Ercan Özdemir; Ahmet Şevki Taşkıran; Erkan Gümüş; Mustafa Ergül

doi:10.7197/cmj.vi.623515

EN

Investigation of anti-epileptic mechanisms of 5HT1A receptor with pentylenetetrazole induced epilepsy model in rats

Abstract

Objective: According to current neurophysiological evidence, the role of 5-hydroxytryptamine (5-HT) receptors in epileptic seizure formation is still not fully elucidated. The aim of this study was to investigate the effects of 5-HT_1A receptor on epileptic seizure with pentylenetetrazole induced epilepsy in rats.

Method: In this study, 28 male Wistar Albino rats weighing 240-260 g were used. Pentylenetetrazole (PTZ, 35 mg/kg, i.p.) was injected to the rats to induce epilepsy and seizure stages were determined according to the Racine scale. Electrodes were placed in the skulls of the animals under stereotaxis for ECoG recording. All the experimental animals were sacrificed by decapitation after ECoG and video recordings. GABA level was measured using the Elisa kit from brain tissues, and c-Fos expression was shown immunohistochemically.

Results: According to the results, it was shown that 8-OH-DPAT increased the time of initial myoclonic jerk (FMJ (p<0.05). However, the number of epileptic spikes was reduced by 8-OH-DPAT (p<0.05). GABA levels decreased in PTZ group (p<0.05). 8-OH-DPAT and WAY-100135 decreased c-Fos expression in all hippocampal areas (p<0.05).

Conclusions: In conclusion, 5-HT_1A receptor agonist 8-OH-DPAT, showed an anti-epileptic effect. The anti-epileptic effects of 5-HT_1Areceptor were found to be inconsistent with changes in GABA level. c-Fos expression is a marker of neuronal activation and may be related to the anti-convulsive effect of 5-HT_1A receptor.

Keywords

Epilepsy,pentylenetetrazole,serotonin,GABA,c-Fos,serotonin receptor agonist

Destekleyen Kurum

Sivas Cumhuriyet Üniversitesi

Proje Numarası

T-739

Kaynakça

1. Bora S, Yeni SN, Gurses C (2008). Epilepsi. 1. Basım, Nobel Tıp Kitabevleri, İstanbul, 707-734.
2. Biziere K, Chambon JP(1987). Animal models of epilepsy and experimental seizures. Rev Neurol. ; 143: 329-40.
3. Akdogan I, Yonguc NG (2011). Experimental epilepsy models and morphologic alterations of experimental epilepsy models in brain and hippocampus, underlying mechanisms of epilepsy. Croatia: InTech, 269-82. 4. Lucki I (1998). The spectrum of behaviors influenced by serotonin. Biol. Psychiatry, 44: 151–162.
5. Tork I (1990). Anatomy of the serotoninergic system. Annals of the New York Academy of Sciences, 600, 9–34.
6. PR Albert, QY Zhou, HH Van Tol (1990). Cloning, functional expression, and mRNA tissue distribution of the rat 5-hydroxytryptamine1A receptor gene, J. Biol. Chem. 265:5825-5832.
7. M Pompeiano, JM Palacios, G Mengod (1992). Distribution and cellular localization of mRNA coding for 5-HT1A receptor in the rat brain: correlation with receptor binding, J. Neurosci. 12: 440-453.
8. AL Garcia-Garcia, A Newman-Tancredi, ED Leonardo (2014). 5-HT(1A) receptors in mood and anxiety: recent insights into autoreceptor versus heteroreceptor function, Psychopharmacology 231, 623-636.
9. PR Albert (2012). Transcriptional regulation of the 5-HT1A receptor: implications for mental illness, Philos. Trans. R. Soc. Lond. B Biol. Sci. 367:2402-2415.

10. KB Fink, M Gothert (2007). 5-HT receptor regulation of neurotransmitter release,Pharmacol. Rev. 59: 360-417.
11. SC Altieri, AL Garcia-Garcia, ED Leonardo, AM Andrews (2013). Rethinking 5-HT(1a) receptors: emerging modes of inhibitory feedback of relevance to emotion-related behavior, ACS Chem. Neurosci. 4: 72-83.
12. Wada Y, Hasegawa H, Nakamura M, Yamaguchi N (1992a). Behavioral and electroencephalographic effects of a serotonin receptor agonist (5-methoxy-N, N-dimethyltryptamine) in a feline model of photosensitive epilepsy. Neurosci Lett., 138(1):115–118.
13. Wada Y, Nakamura M, Hasegawa H, Yamaguchi N (1993). Intra-hippocampal injection of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) inhibits partial and generalized seizures induced by kindling stimulation in cats. Neurosci Lett., 159(1–2):179–182.
14. Andrade R, Malenka RC, Nicoll RA (1986). A G protein couples serotonin and GABAB receptors to the same channels in hippocampus. Science, 234(4781):1261–1265.
15. RJ Racine (1972).Modification of seizure activity by electrical stimulation: II. Motor seizure Electroencephalogr Clin Neurophysiol, 32, 281-294.
16. Bonsi P, Cuomo D (2007). Endogenous serotonin excites striatal cholinergic interneurons via the activation of 5-HT2C,5-HT6, and 5-HT7 serotonin receptors: implications for extrapyramidal side effects of serotonin reuptake inhibitors. N.pharmacol.32:1840-5.
17. Hedges D, Jeppson K, Whitehead P (2003). Antipsychotic medication and seizures: a review. Drugs Today (Barc), 39(7):551–557.
18. Bahremand A, Payandemehr B (2011). The role of 5-HT(3) receptors in the additive anticonvulsant effects of citalopram and morphine on pentylenetetrazole-induced clonic seizures in mice. Epilepsy Behav., 21(2):122–127. epilepsy. J Neurochem., 100(4):857–873. 20. Goodman LS, Gilman A, Brunton LL, Lazo JS, Parker KL (2006). Goodman and Gilman’s the pharmacological basis of therapeutics 11th edn. McGraw-Hill, New York. 3(19):501-527.
21. Gerber K, Filakovszky J, Halasz P, Bagdy G (1998). The 5-HT1A agonist 8-OH-DPAT increases the number of spike-wave discharges in a genetic rat model of absence epilepsy. Brain Res., 807(1–2):243–245.
22. Graf M, Jakus R, Kantor S, Levay G, Bagdy G (2004). Selective 5-HT1A and 5-HT7 antagonists decrease epileptic activity in the WAG/Rij rat model of absence epilepsy. Neurosci Lett., 359(1–2):45–48.
23. Filakovszky J, Kantor S, Halasz P, Bagdy G (2001). 8-OH-DPAT and MK-801 affect epileptic activity independently of vigilance. Neurochem Int., 38(7):551–556. 24. Jakus R, Graf M (2004). Effect of two noncompetitive AMPA receptor antagonists GYKI 52466 and GYKI 53405 on vigilance, behavior and spike-wave discharges in a genetic rat model of absence epilepsy. Brain Res., 2:236–244.
25. Ohno Y, Sofue N (2010). Serotonergic modulation of absence-like seizures in groggy rats: a novel rat model of absence epilepsy. J Pharmacol Sci., 114(1):99–105.
26. Wada Y, Shiraishi J, Nakamura M, Koshino Y (1997b). Role of serotonin receptor subtypes in the development of amygdaloid kindling in rats. Brain Res., 747(2):338–342. 27. Wesolowska A, Nikiforuk A, Chojnacka-Wojcik E (2006). Anticonvulsant effect of the selective 5-HT1B receptor agonist CP 94253 in mice. Eur J Pharmacol, 541(1–2):57–63.
28. Lopez-Meraz ML, Gonzalez-Trujano ME, Neri-Bazan L, Hong E, Rocha LL (2005). 5-HT1A receptor agonists modify epileptic seizures in three experimental models in rats. Neuropharmacology, 49(3):367–375.
29. Heydari A, Davoudi S (2017). The effect of sertraline and 8-OH-DPAT on the PTZ induced seizure threshold: Role of the nitrergic system. Seizure, 45:119-124.
30. Salgado-Commissariat D, Alkadhi KA (1997). Serotonin inhibits epileptiform discharge by activation of 5-HT1A receptors in CA1 pyramidal neurons. Neuropharmacology, 36(11–12):1705–1712.
31. Yi Yang, Yi Guo (2014). Serotonin 1A receptor inhibits the status epilepticus induced by lithium-pilocarpine in rats. Neurosci Bull, 30(3): 401–408.
32. Sarnyai Z, Sibille EL, Pavlides C, Fenster RJ, McEwen BS, Toth M (2000). Impaired hippocampal-dependent learning and functional abnormalities in the hippocampus in mice lacking serotonin(1A) receptors. Proc Natl Acad Sci USA 97, (26):14731–14736.
33. Lin X, Itoga CA, Taha S (2018). c-Fos mapping of brain regions activated by multi-modal and electric foot shock stress. Neurobiol Stress, 8:92–102.
34. Marques-Carneiro JE, Nehlig A, Cassel JC (2017). Neurochemical changes and c-Fos mapping in the brain after carisbamate treatment of rats subjected to lithium-pilocarpine-induced status epilepticus. Pharmaceuticals (Basel), 10(4):1–14.
35. Samokhina E, Samokhin A (2018). Neuropathological profile of the pentylenetetrazol (PTZ) kindling model. Int J Neurosci., 1–11.

Ayrıntılar

Birincil Dil

İngilizce

Konular

Sağlık Kurumları Yönetimi

Bölüm

Araştırma Makalesi

Yazarlar

Bilal Şahin ^*
0000-0002-4419-1385
Türkiye

Ercan Özdemir
0000-0001-8231-1053

Ahmet Şevki Taşkıran
0000-0002-5810-8415

Erkan Gümüş
0000-0001-6432-7457

Mustafa Ergül
0000-0003-4303-2996

Yayımlanma Tarihi

30 Eylül 2019

Gönderilme Tarihi

23 Eylül 2019

Kabul Tarihi

26 Eylül 2019

Yayımlandığı Sayı

Yıl 2019 Cilt: 41 Sayı: 3

DOI

https://doi.org/10.7197/cmj.vi.623515

IZ

https://izlik.org/JA52LU97HU

Kaynak Göster

RIS / Bibtex

AMA

1.Şahin B, Özdemir E, Taşkıran AŞ, Gümüş E, Ergül M. Investigation of anti-epileptic mechanisms of 5HT1A receptor with pentylenetetrazole induced epilepsy model in rats. CMJ. 2019;41(3):490-499. doi:10.7197/cmj.vi.623515