Thu, Jan 2, 2025
[Archive]
Volume 26, Issue 118 (September & October 2018)
J Adv Med Biomed Res 2018, 26(118): 21-27 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Zareie P, Sadegh M, Moradi-Chameh H. 2-Arachidonoylglycerol enrichment Reduced Epileptiform Activity of the Rat Hippocampus induced with Pentylenetetrazol. J Adv Med Biomed Res 2018; 26 (118) :21-27
URL: http://journal.zums.ac.ir/article-1-4878-en.html
URL: http://journal.zums.ac.ir/article-1-4878-en.html
1- Dept of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
2- Dept. of Fundamental Neurobiology, Krembil Research Institute, Toronto, Ontario, Canada ,m.sadegh@arakmu.ac.ir
3- Dept. of Fundamental Neurobiology, Krembil Research Institute, Toronto, Ontario, Canada
2- Dept. of Fundamental Neurobiology, Krembil Research Institute, Toronto, Ontario, Canada ,
3- Dept. of Fundamental Neurobiology, Krembil Research Institute, Toronto, Ontario, Canada
Abstract: (145607 Views)
Background and Objective: 2-arachidonoylglycerol (2-AG) and anandamide (AEA) are two major endocannabinoids. Using inhibitors of the enzymatic pathways involved in the elimination of 2-AG and AEA as well as synthetic 2-AG, we examined the effectiveness of these endocannabinoids on epileptiform activity induced in Wistar rats by pentylenetetrazol (PTZ).
Material and Methods: Adult male Wistar rats were used in this study. Epileptiform activity was induced in dult male Wistar rats by PTZ injection (20 mg/kg, i.p.). To inhibit 2-AG degradation WWL70 and JJKK048 (JJKK048: 1 mg/kg, WWL70: 5 mg/kg, i.p.) were used. To inhibit AEA elimination, URB597 and LY2183240 (URB597: 1 mg/kg, LY2183240: 2.5 mg/kg, i.p.) were used. Synthetic 2-AG was also examined (1 mg/kg, i.p.) before the PTZ injection. All drugs were dissolved in DMSO as vehicle and injected (i.p.) 15 minutes before the PTZ injection. Latency to onset and duration of the epileptiform activity were considered for statistical analysis.
Results: Injection of (JJKK048+WWL70) before the PTZ significantly increased latency to onset of the epileptiform activity (p<0.01), while reduced duration of the epileptiform activity in comparison to the vehicle (p<0.05). In addition, 2-AG administration significantly increased latency to onset of the epileptiform activity (p<0.05) and reduced duration of the epileptiform activity in comparison to the vehicle (p<0.01). However, these indexes did not show significant changes when URB597+LY2183240 were injected before the PTZ (p>0.05).
Conclusion: It seems increased level of 2-AG but not AEA,effectively decreases PTZ induced epileptiform activity of the hippocampus.
Material and Methods: Adult male Wistar rats were used in this study. Epileptiform activity was induced in dult male Wistar rats by PTZ injection (20 mg/kg, i.p.). To inhibit 2-AG degradation WWL70 and JJKK048 (JJKK048: 1 mg/kg, WWL70: 5 mg/kg, i.p.) were used. To inhibit AEA elimination, URB597 and LY2183240 (URB597: 1 mg/kg, LY2183240: 2.5 mg/kg, i.p.) were used. Synthetic 2-AG was also examined (1 mg/kg, i.p.) before the PTZ injection. All drugs were dissolved in DMSO as vehicle and injected (i.p.) 15 minutes before the PTZ injection. Latency to onset and duration of the epileptiform activity were considered for statistical analysis.
Results: Injection of (JJKK048+WWL70) before the PTZ significantly increased latency to onset of the epileptiform activity (p<0.01), while reduced duration of the epileptiform activity in comparison to the vehicle (p<0.05). In addition, 2-AG administration significantly increased latency to onset of the epileptiform activity (p<0.05) and reduced duration of the epileptiform activity in comparison to the vehicle (p<0.01). However, these indexes did not show significant changes when URB597+LY2183240 were injected before the PTZ (p>0.05).
Conclusion: It seems increased level of 2-AG but not AEA,effectively decreases PTZ induced epileptiform activity of the hippocampus.
Full-Text [PDF 430 kb]
(156877 Downloads)
| | Full-Text (HTML) (3190 Views)
✅ It seems increased level of 2-AG but not AEA,effectively decreases PTZ induced epileptiform activity of the hippocampus.
Type of Study: Original Article |
Subject:
Medical Biology
Received: 2017/09/26 | Accepted: 2018/01/24 | Published: 2019/08/3
Received: 2017/09/26 | Accepted: 2018/01/24 | Published: 2019/08/3
References
1. de Boer HM, Mula M, Sander JW. The global burden and stigma of epilepsy. Epilepsy Behav. 2008; 12(4): 540-6. [DOI:10.1016/j.yebeh.2007.12.019] [PMID]
2. Hitiris N, Mohanraj R, Norrie J, Sills GJ, Brodie MJ. Predictors of pharmacoresistant epilepsy. Epilepsy Res. 2007; 75: 192-6. [DOI:10.1016/j.eplepsyres.2007.06.003] [PMID]
3. Hill AJ, Williams CM, Whalley BJ, Stephens GJ. Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacol Ther. 2012; 133(1): 79-97. [DOI:10.1016/j.pharmthera.2011.09.002] [PMID]
4. Russo EB. Cannabis and epilepsy: An ancient treatment returns to the fore. Epilepsy Behav. 2017; 70: 292-7. [DOI:10.1016/j.yebeh.2016.09.040] [PMID]
5. dos Santos RG, Hallak JE, Leite JP, Zuardi AW, Crippa JA. Phytocannabinoids and epilepsy. J Clin Pharm Ther. 2014; 40: 135-43. [DOI:10.1111/jcpt.12235] [PMID]
6. Ligresti A, Cascio MG, Di Marzo V. Endocannabinoid metabolic pathways and enzymes. Curr Drug Targets CNS Neurol Disord. 2005; 4(6): 615-23. [DOI:10.2174/156800705774933104] [PMID]
7. Battista N, Di Tommaso M, Bari M, Maccarrone M. The endocannabinoid system: an overview. Front Behav Neurosci. 2012; 6: 9. [DOI:10.3389/fnbeh.2012.00009] [PMID] [PMCID]
8. Savinainen J, Saario S, Laitinen J. The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2‐arachidonoylglycerol signalling through cannabinoid receptors. Acta physiologica. 2012; 204(2): 267-76. [DOI:10.1111/j.1748-1716.2011.02280.x] [PMID] [PMCID]
9. Basavarajappa BS. Critical enzymes involved in endocannabinoid metabolism. Protein Pept Lett. 2007; 14(3): 237-46. [DOI:10.2174/092986607780090829]
10. Sugaya Y, Yamazaki M, Uchigashima M, et al. Crucial Roles of the Endocannabinoid 2-Arachidonoylglycerol in the Suppression of Epileptic Seizures. Cell Rep. 2016; 16(5): 1405-15. [DOI:10.1016/j.celrep.2016.06.083] [PMID]
11. Fezza F, Marrone MC, Avvisati R, et al. Distinct modulation of the endocannabinoid system upon kainic acid-induced in vivo seizures and in vitro epileptiform bursting. Mol Cell Neurosci. 2014; 62: 1-9. [DOI:10.1016/j.mcn.2014.07.003] [PMID]
12. Zareie P, Sadegh M, Palizvan M. The effect of 2-archidonyl glycerol (2-AG) as an endocannabinoid on tonic- clonic seizures induced by pentylenetetrazol (PTZ). Zanjan Univ Med Sci J. 2017; 25(109): 11-22.
13. Zareie P, Sadegh M, Palizvan M. Investigating the effect of enzymatic elimination of endocannabinoids inhibitors on tonic- colonic seizure provoked by PTZ. Babol Univ Med Sci. 2016; 18(12): 49-56.
14. Naydenov AV, Horne EA, Cheah CS, et al. ABHD6 blockade exerts antiepileptic activity in PTZ-induced seizures and in spontaneous seizures in R6/2 mice. Neuron. 2014; 83(2): 361-71. [DOI:10.1016/j.neuron.2014.06.030] [PMID] [PMCID]
15. Aaltonen N, Savinainen JR, Ribas CR, et al. Piperazine and piperidine triazole ureas as ultrapotent and highly selective inhibitors of monoacylglycerol lipase. Chem Biol. 2013; 20(3): 379-90. [DOI:10.1016/j.chembiol.2013.01.012] [PMID]
16. Wen J, Ribeiro R, Tanaka M, Zhang Y. Activation of CB2 receptor is required for the therapeutic effect of ABHD6 inhibition in experimental autoimmune encephalomyelitis. Neuropharmacol. 2015; 99: 196-209. [DOI:10.1016/j.neuropharm.2015.07.010] [PMID]
17. Hasanein P, Ghafari-Vahed M. Fatty acid amide hydrolase inhibitor URB597 prevented tolerance and cognitive deficits induced by chronic morphine administration in rats. Behav Pharmacol. 2016;27(1): 37-43. [DOI:10.1097/FBP.0000000000000179] [PMID]
18. Maione S, Morera E, Marabese I, et al. Antinociceptive effects of tetrazole inhibitors of endocannabinoid inactivation: cannabinoid and non-cannabinoid receptor-mediated mechanisms. Br J Pharmacol. 2008; 155(5): 775-82. [DOI:10.1038/bjp.2008.308] [PMID] [PMCID]
19. Wakley AA, Rasmussen EB. Effects of cannabinoid drugs on the reinforcing properties of food in gestationally undernourished rats. Pharmacol Biochem Behav. 2009; 94(1): 30-6. [DOI:10.1016/j.pbb.2009.07.002] [PMID]
20. Depaulis A, Snead OC, Marescaux C, Vergnes M. Suppressive effects of intranigral injection of muscimol in three models of generalized non-convulsive epilepsy induced by chemical agents. Brain Res. 1989; 25; 498(1): 64-72. [DOI:10.1016/0006-8993(89)90399-5]
21. Snead OC, Banerjee PK, Burnham M, Hampson D. Modulation of absence seizures by the GABA(A) receptor: a critical rolefor metabotropic glutamate receptor 4 (mGluR4). J Neurosci. 2000; 20(16): 6218-24. [DOI:10.1523/JNEUROSCI.20-16-06218.2000]
22. Schwenk J, Harmel N, Brechet A, et al. High-resolution proteomics unravel architecture and molecular diversity of native AMPA receptor complexes. Neuron. 2012; 24; 74(4): 621-33. [DOI:10.1016/j.neuron.2012.03.034] [PMID]
23. Ludanyi A, Eross L, Czirjak S, et al. Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus. J Neurosci. 2008; 28(12): 2976-90. [DOI:10.1523/JNEUROSCI.4465-07.2008] [PMID]
24. Hill TD, Cascio MG, Romano B, et al. Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism. Br J Pharmacol. 2013; 170(3): 679-92. [DOI:10.1111/bph.12321] [PMID] [PMCID]
25. Griebel G, Pichat P, Beeske S, et al. Selective blockade of the hydrolysis of the endocannabinoid 2-arachidonoylglycerol impairs learning and memory performance while producing antinociceptive activity in rodents. Sci Rep. 2015; 5: 7642. [DOI:10.1038/srep07642] [PMID] [PMCID]
26. Sigel E, Baur R, Racz I, et al. The major central endocannabinoid directly acts at GABA(A) receptors. Proc Natl Acad Sci U S A. 2011;108(44): 18150-5. [DOI:10.1073/pnas.1113444108] [PMID] [PMCID]
27. Citraro R, Russo E, Scicchitano F, et al. Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-alpha receptor activation in a genetic model of absence epilepsy. Neuropharmacol. 2013; 69: 115-26. [DOI:10.1016/j.neuropharm.2012.11.017] [PMID]
28. Deshpande LS, Blair RE, Ziobro JM, Sombati S, Martin BR, DeLorenzo RJ. Endocannabinoids block status epilepticus in cultured hippocampal neurons. Europ J Pharmacol. 2007; 558: 52-9. [DOI:10.1016/j.ejphar.2006.11.030] [PMID] [PMCID]
29. Clement AB, Hawkins EG, Lichtman AH, Cravatt BF. Increased seizure susceptibility and proconvulsant activity of anandamide in mice lacking fatty acid amide hydrolase. J Neurosci. 2003; 23(9): 3916-23. [DOI:10.1523/JNEUROSCI.23-09-03916.2003]
30. Corvino V, Marchese E, Podda MV, et al. The neurogenic effects of exogenous neuropeptide Y: early molecular events and long-lasting effects in the hippocampus of trimethyltin-treated rats. PloS one. 2014; 9(2): e88294. [DOI:10.1371/journal.pone.0088294] [PMID] [PMCID]
31. Hoover HS, Blankman JL, Niessen S, Cravatt BF. Selectivity of inhibitors of endocannabinoid biosynthesis evaluated by activity-based protein profiling. Bioorg Med Chem Lett. 2008; 18(22): 5838-41. [DOI:10.1016/j.bmcl.2008.06.091] [PMID] [PMCID]
32. Ma L, Wang L, Yang F, et al. Disease‐modifying effects of RHC80267 and JZL184 in a pilocarpine mouse model of temporal lobe epilepsy. CNS Neuro Sci Ther. 2014; 20(10): 905-15. [DOI:10.1111/cns.12302] [PMID] [PMCID]
33. Curia G, Longo D, Biagini G, Jones RS, Avoli M. The pilocarpine model of temporal lobe epilepsy. J Neuro Sci Methods. 2008; 30; 172(2-4): 143-57. [DOI:10.1016/j.jneumeth.2008.04.019] [PMID] [PMCID]
34. Löscher W. Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs. Seizure. 2011; 20(5): 359-68. [DOI:10.1016/j.seizure.2011.01.003] [PMID]
35. Blair RE, Deshpande LS, Sombati S, Elphick MR, Martin BR, DeLorenzo RJ. Prolonged exposure to WIN55,212-2 causes downregulation of the CB1 receptor and the development of tolerance to its anticonvulsant effects in the hippocampal neuronal culture model of acquired epilepsy. Neuropharmacology. 2009; 57(3): 208-18. [DOI:10.1016/j.neuropharm.2009.06.007] [PMID] [PMCID]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
Copyright Policy
