Volume 22, Issue 5 (Dec - Jan 2018)                   J Qazvin Univ Med Sci 2018, 22(5): 4-13 | Back to browse issues page

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Esmaili Z, Heydari A. Involvement of nitric oxide in the effect of caffeine on the pentylenetetrazole-induced seizure threshold in mice . J Qazvin Univ Med Sci. 2018; 22 (5) :4-13
URL: http://journal.qums.ac.ir/article-1-2728-en.html
1- Student Research Committee, Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran
2- Student Research Committee, Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran , heydariazh@gmail.com
Abstract:   (2340 Views)

Background: Effect of caffeine on seizure is controversial in animal models of epilepsy. Caffeine is non-selective antagonist of A1 and A2A adenosine receptors. Meanwhile, nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) pathway is partly involved in the central effects of caffeine.
Objective: The aim of this study was to investigate the effect of acute caffeine administration on seizure threshold and levels of nitric oxide metabolites in pentylenetetrazole (PTZ) model in mice.
Methods: In this study, 35 NMRI mice (25-30 g) were divided into 5 groups (7 animals in each group). Clonic seizure threshold induced by PTZ was assessed in intact control group or 30 min after acute intraperitoneal administration of caffeine (5, 100, and 150 mg/kg) or saline. Nitric oxide metabolites (NOx) were measured in the brain tissues of all groups at the end of experiments. Data were analyzed by ANOVA and followed Tukey test for multiple comparisons.
Findings: Acute administration of 5 mg/kg of caffeine significantly decreased seizure threshold compared to saline (P<0.01). While 100 and 150 mg/kg of caffeine did not change seizure threshold. NOx levels significantly decreased following acute administration of caffeine (100 and 150 mg/kg) compared to saline (P<0.05).
Conclusion: The results of study showed that different doses of caffeine had different effects. It seems that effect of higher doses of caffeine is partly mediated through modulation of nitric oxide pathway.

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Type of Study: Research | Subject: Physiology

1. Forsgren L, Beghi E, Oun A, Sillanpaa M. The epidemiology of epilepsy in Europe- a systematic review. Eur J Neurol 2005; 12(4): 245-53. [DOI] [PubMed]
2. Scott RA, Lhatoo SD, Sander JW. The treatment of epilepsy in developing countries: where do we go from here? Bull World Health Organ 2001; 79(4): 344-51. [PubMed]
3. Butt MS, Sultan MT. Coffee and its consumption: benefits and risks. Crit Rev Food Sci Nutr 2011; 51(4): 363-73. [DOI] [PubMed]
4. Gonzalez de Mejia E, Ramirez-Mares MV. Impact of caffeine and coffee on our health. Trends Endocrinol Metab 2014; 25(10): 489-92. [DOI] [PubMed]
5. Wei CJ, Li W, Chen JF. Normal and abnormal functions of adenosine receptors in the central nervous system revealed by genetic knockout studies. Biochim Biophys Acta 2011; 1808(5): 1358-79. [DOI] [PubMed]
6. El Yacoubi M, Ledent C, Parmentier M, Bertorelli R, Ongini E, Costentin J, et al. Adenosine A2A receptor antagonists are potential antidepressants: evidence based on pharmacology and A2A receptor knockout mice. Br J Pharmacol 2001; 134(1): 68-77. [DOI] [PubMed]
7. Bonilha L, Li LM. Heavy coffee drinking and epilepsy. Seizure 2004; 13(4): 284-5. [DOI] [PubMed]
8. Loscher W. Preclinical assessment of proconvulsant drug activity and its relevance for predicting adverse events in humans. Eur J Pharmacol 2009; 610(1-3): 1-11. [DOI] [PubMed]
9. Iyadurai SJ, Chung SS. New-onset seizures in adults: possible association with consumption of popular energy drinks. Epilepsy Behav 2007; 10(3): 504-8. [DOI] [PubMed]
10. Luszczki JJ, Zuchora M, Sawicka KM, Kozinska J, Czuczwar SJ. Acute exposure to caffeine decreases the anticonvulsant action of ethosuximide, but not that of clonazepam, phenobarbital and valproate against pentetrazole-induced seizures in mice. Pharmacol Rep 2006; 58(5): 652-9. [PubMed]
11. Dworetzky BA, Bromfield EB, Townsend MK, Kang JH. A prospective study of smoking, caffeine, and alcohol as risk factors for seizures or epilepsy in young adult women: data from the Nurses' Health Study II. Epilepsia 2010; 51(2): 198-205. [DOI] [PubMed]
12. El Yacoubi M, Ledent C, Parmentier M, Costentin J, Vaugeois JM. Evidence for the involvement of the adenosine A(2A) receptor in the lowered susceptibility to pentylenetetrazol-induced seizures produced in mice by long-term treatment with caffeine. Neuropharmacology 2008; 55(1): 35-40. [DOI] [PubMed]
13. Svenningsson P, Nomikos GG, Fredholm BB. The stimulatory action and the development of tolerance to caffeine is associated with alterations in gene expression in specific brain regions. J Neurosci 1999; 19(10): 4011-22. [DOI] [PubMed]
14. Germe K, Faure JB, Koning E, Nehlig A. Effect of caffeine and adenosine receptor ligands on the expression of spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Epilepsy Res 2015; 110: 105-14. [DOI] [PubMed]
15. Klinger M, Freissmuth M, Nanoff C. Adenosine receptors: G protein-mediated signalling and the role of accessory proteins. Cell Signal 2002; 14(2): 99-108. doi: 10.1016 /S0898-6568(01)00235-2. [PubMed]
16. Carmeli E, Beiker R, Morad M. Nitric oxide and interlukin-6 levels in intellectual disability adults with epilepsy. Res Dev Disabil 2009; 30(3): 567-71. doi: 10.1016/j. ridd.2008.08.004. [PubMed]
17. Akula KK, Dhir A, Kulkarni SK. Nitric oxide signaling pathway in the anti-convulsant effect of adenosine against pentylenetetrazol-induced seizure threshold in mice. Eur J Pharmacol 2008; 587(1-3): 129-34. [DOI] [PubMed]
18. Bruce C, Yates DH, Thomas PS. Caffeine decreases exhaled nitric oxide. Thorax 2002; 57(4): 361-3. [DOI] [PubMed]
19. Jargiello-Baszak M, Chroscinska- Krawczyk M, Andres-Mach M, Luszczki JJ, Czuczwar SJ. Influence of caffeine on the protective activity of gabapentin and topiramate in a mouse model of generalized tonic-clonic seizures. Pharmacol Rep 2016; 68(4): 680-5. doi: 10.1016/j.pharep.2016.03.011. [PubMed]
20. Miranda KM, Espey 20. MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 2001; 5(1): 62-71. [DOI] [PubMed]
21. Heydari A, Davoudi S. The effect of sertraline and 8-OH-DPAT on the PTZ_induced seizure threshold: Role of the nitrergic system. Seizure 2017; 45: 119-24. [DOI] [PubMed]
22. Esmaili Z, Heydari A. Effect of acute caffeine administration on PTZ-induced seizure threshold in mice: Involvement of adenosine receptors and NO-cGMP signaling pathway. Epilepsy Res 2019;149:1-8. [DOI] [PubMed]
23. Bankstahl M, Bankstahl JP, Bloms-Funke P, Loscher W. Striking differences in proconvulsant-induced alterations of seizure threshold in two rat models. Neurotoxicology 2012; 33(1): 127-37. [DOI] [PubMed]
24. De Sarro A, Grasso S, Zappala M, Nava F, De Sarro G. Convulsant effects of some xanthine derivatives in genetically epilepsy-prone rats. Naunyn Schmiedebergs Arch Pharmacol 1997; 356(1): 48-55. [DOI] [PubMed]
25. Marangos PJ, Martino AM, Paul SM, Skolnick P. The benzodiazepines and inosine antagonize caffeine-induced seizures. Psychopharmacology (Berl) 1981; 72(3): 269-73. [DOI] [PubMed]
26. Ongini E, Fredholm BB. Pharmacology of adenosine A2A receptors. Trends Pharmacol Sci 1996; 17(10): 364-72. [DOI] [PubMed]
27. Jacobson KA. Introduction to adenosine receptors as therapeutic targets. Handb Exp Pharmacol 2009(193): 1-24. [DOI] [PubMed]
28. Fedele DE, Li T, Lan JQ, Fredholm BB, Boison D. Adenosine A1 receptors are crucial in keeping an epileptic focus localized. Exp Neurol 2006; 200(1): 184-90. [DOI] [PubMed]
29. Gouder N, Fritschy JM, Boison D. Seizure suppression by adenosine A1 receptor activation in a mouse model of pharmacoresistant epilepsy. Epilepsia 2003; 44(7): 877-85. [DOI] [PubMed]
30. Chroscinska-Krawczyk M, Jargiello-Baszak M, Walek M, Tylus B, Czuczwar SJ. Caffeine and the anticonvulsant potency of antiepileptic drugs: experimental and clinical data. Pharmacological Rep 2011; 63(1): 12-8. [DOI] [PubMed]
31. Borowicz KK, Luszczki J, Czuczwar SJ. 2-Chloroadenosine, a preferential agonist of adenosine A1 receptors, enhances the anticonvulsant activity of carbamazepine and clonazepam in mice. Eur Neuropsychopharmacol 2002; 12(2): 173-9. [DOI] [PubMed]
32. Riazi K, Roshanpour M, Rafiei-Tabatabaei N, Homayoun H, Ebrahimi F, Dehpour AR. The proconvulsant effect of sildenafil in mice: role of nitric oxide-cGMP pathway. Br J Pharmacol 2006; 147(8): 935-43. [DOI] [PubMed]
33. Weber M, Lauer N, Mülsch A, Kojda G. The effect of peroxynitrite on the catalytic activity of soluble guanylyl cyclase. Free Radic Biol Med 2001; 31(11): 1360-67. [DOI] [PubMed]
34. Samsonsen C, Brathen G, Reimers A, Helde G, Brodtkorb E. Is dietary caffeine involved in seizure precipitation? Epilepsy Behav 2013; 28(2): 147-50. [DOI] [PubMed]
35. Boison D. Methylxanthines, seizures, and excitotoxicity. Handb Exp Pharmacol 2011(200): 251-66. doi: 10.1007/978-3-642-13443-2_9. [PubMed]

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