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:: Volume 22, Issue 4 (Bimonthly 2018) ::
Feyz 2018, 22(4): 339-345 Back to browse issues page
The effect of chronic caffeine intake on pentylenetetrazole (PTZ)-induced seizure threshold and nitric oxide metabolites in mice
Zahra Esmaili , Azhdar Heydari *
Physiology Research Center, Kashan University of Medical Sciences, Kashan, I. R. Iran. , heydariazh@gmail.com
Abstract:   (222 Views)
Background: Long-term caffeine intake decreases seizure susceptibility and has protective effect. This protective effect of caffeine may be due to the blockade of A2A adenosine receptors. Considering that activation of adenosine A2A receptors elevates nitric oxide production, the aim of the present study was to investigate the effect of chronic caffeine intake on the pentylenetetrazole (PTZ)-induced seizure threshold and measurement of nitric oxide metabolites levels in mice.
Materials and Methods: In this study, NMRI male mice (weighing 25-30 g) were divided into 3 groups including one control and two experimental groups (n=9 in each group). PTZ- induced clonic seizure was measured following oral intake of caffeine in experimental groups (100 and 300 mg/L in the drinking water) or only tap water in the control group for 90 days. Measurement of nitric oxide metabolites in the brain tissues was done at the end of the experiments using the Greiss method.
Results: The chronic caffeine intake at concentrations of 100 and 300 mg/L in the drinking water for 90 days did not change the seizure threshold. On the other hand, both concentrations of caffeine significantly decreased nitric oxide metabolites levels compared to the control group (P<0.05).
Conclusion: The results of this study confirmed and extended previous studies that chronic caffeine intake has no effect on seizure. Reduced levels of nitric oxide metabolites and resultant decreased neuronal excitability may be the main protective mechanism of the chronic caffeine intake. Blockade of the A2A adenosine receptors following the chronic caffeine intake may be involved in decreased levels of nitric oxide metabolites.
Keywords: Caffeine, Seizure, Pentylenetetrazole, Nitric oxide, Adenosine receptor
Full-Text [PDF 253 kb]   (20 Downloads)    
Type of Study: Research | Subject: General
Received: 2018/05/28 | Accepted: 2018/06/24 | Published: 2018/10/6
1. Györffy B, Kovács Z, Gulyássy P, Simor A, Völgyi K, Orbán G, et al. Brain protein expression changes in WAG/Rij rats, a genetic rat model of absence epilepsy after peripheral lipopolysaccharide treatment. Brain Behav Immun 2014; 35: 86-95.
2. Bernstein GA, Carroll ME, Thuras PD, Cosgrove KP, Roth ME. Caffeine dependence in teenagers. Drug Alcohol Depend 2002; 66(1): 1-6.
3. 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.
4. Luszczki JJ, Zuchora M, Sawicka KM, Kozi‌ńska 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.
5. Bonilha L, Li LM. Heavy coffee drinking and epilepsy. Seizure 2004; 13(4): 284-5.
6. Löscher 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.
7. Chrościńska-Krawczyk M, Jargiełło-Baszak M, Wałek M, Tylus B, Czuczwar SJ. Caffeine and the anticonvulsant potency of antiepileptic drugs: experimental and clinical data. Pharmacol Rep 2011; 63(1): 12-8.
8. Calabrò RS, Italiano D, Gervasi G, Bramanti P. Single tonic–clonic seizure after energy drink ab‌use. Epilepsy Behav 2012; 23(3): 384-5.
9. Bankstahl M, Bankstahl JP, Bloms-Funke P, Löscher W. Striking differences in proconvulsant-induced alterations of seizure threshold in two rat models. Neurotoxicology 2012; 33(1): 127-37.
10. Fredholm BB. Adenosine receptors as drug targets. Exp Cell Res 2010; 316(8): 1284-8.
11. 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.
12. Boison D. Methylxanthines, seizures, and excito‌toxicity. Handb Exp Pharmacol 2011; (200): 251-66.
13. Etherington AV, Frenguelli BG. Endogenous adenosine modulates epileptiform activity in rat hippocampus in a receptor subtype-dependent man‌ner. Eur J Neurosci 2004; 19(9): 2539-50.
14. Zandieh A, Maleki F, Hajimirzabeigi A, Zan‌dieh B, Khalilzadeh O, Dehpour AR. Anti‌con‌vulsant effect of celecoxib on pentylenetetrazole-induced convulsion: Modulation by NO pathway. Acta Neurobiol Exp 2010; 70(4): 390-7.
15. Akula KK, Dhir A, Kulkarni S. 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.
16. Bruce C, Yates DH, Thomas PS. Caffeine decre‌ases exhaled nitric oxide. Thorax 2002; 57(4): 361-3.
17. Ardais A, Borges MF, Rocha AS, Sallaberry C, Cunha R, Porciúncula L. Caffeine triggers behav‌ioral and neurochemical alterations in adolescent rats. Neuroscience 2014; 270: 27-39.
18. 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.
19. Huang RQ, Bell-Horner CL, Dibas MI, Covey DF, Drewe JA, Dillon GH. Pentylenetetrazole-induced inhibition of recombinant gamma-amino‌butyric acid type A (GABA(A)) receptors: mecha‌nism and site of action. J Pharmacol Exp Ther 2001; 298(3): 986-95.
20. Porciúncula LO, Sallaberry C, Mioranzza S, Botton PH, Rosemberg DB. The Janus face of caffeine. Neurochem Int 2013; 63(6): 594-609.
21. Chrościńska-Krawczyk M, Jargiełło-Baszak M, Andres-Mach M, Łuszczki 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.
22. Germé 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.
23. Matovu D, Alele PE. Seizure vulnerability and anxiety responses following chronic co-admini‌st‌ration and acute withdrawal of caffeine and ethanol in a rat model. J Basic Clin Physiol Pharmacol 2018; 26; 29(1): 1-10.
24. Mareš P. A1 not A2A adenosine receptors play a role in cortical epileptic afterdischarges in imma‌ture rats. J Neural Transm 2014; 121(11): 1329-36.
25. Cunha RA, Agostinho PM. Chronic caffeine cons‌u‌mption prevents memory disturbance in different animal models of memory decline. J Alzheimers Dis 2010; 20(1): S95-116.
26. Tavares C, Sakata RK. Caffeine in the treat‌ment of pain. Rev Bras Anestesiol 2012; 62(3): 387-401.
27. Rigoulot MA, Leroy C, Koning E, Ferrandon A, Nehlig A. Prolonged low-dose caffeine exposure protects against hippocampal damage but not against the occurrence of epilepsy in the lithium-pilocarpine model in the rat. Epilepsia 2003; 44(4): 529-35.
28. 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.
29. Vincent SR. Nitric oxide neurons and neurotra‌nsmission. Prog Neurobiol 2010; 90(2): 246-55.
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Esmaili Z, Heydari A. The effect of chronic caffeine intake on pentylenetetrazole (PTZ)-induced seizure threshold and nitric oxide metabolites in mice. Feyz. 2018; 22 (4) :339-345
URL: http://feyz.kaums.ac.ir/article-1-3617-en.html

Volume 22, Issue 4 (Bimonthly 2018) Back to browse issues page
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