Top

Published in:

01-06-2018 | Original Article

Anticonvulsive effects of endocannabinoids; an investigation to determine the role of regulatory components of endocannabinoid metabolism in the Pentylenetetrazol induced tonic- clonic seizures

Authors: Parisa Zareie, Mehdi Sadegh, Mohammad Reza Palizvan, Homeira Moradi-Chameh

Published in: Metabolic Brain Disease | Issue 3/2018

Abstract

2-Arachidonoylglycerol (2-AG) and anandamide are two major endocannabinoids produced, released and eliminated by metabolic pathways. Anticonvulsive effect of 2-AG and CB1 receptor is well-established. Herein, we designed to investigate the anticonvulsive influence of key components of the 2-AG and anandamide metabolism. Tonic-clonic seizures were induced by an injection of Pentylenetetrazol (80 mg/kg, i.p.) in adult male Wistar rats. Delay and duration for the seizure stages were considered for analysis. Monoacylglycerol lipase blocker (JJKK048; 1 mg/kg) or alpha/beta hydroxylase domain 6 blocker (WWL70; 5 mg/kg) were administrated alone or with 2-AG to evaluate the anticonvulsive potential of these enzymes. To determine the CB1 receptor involvement, its blocker (MJ15; 3 mg/kg) was administrated associated with JJKK048 or WWL70. To assess anandamide anticonvulsive effect, anandamide membrane transporter blocker (LY21813240; 2.5 mg/kg) was used alone or associated with MJ15. Also, fatty acid amide hydrolase blocker (URB597; 1 mg/kg; to prevent intracellular anandamide hydrolysis) were used alone or with AMG21629 (transient receptor potential vanilloid; TRPV1 antagonist; 3 mg/kg). All compounds were dissolved in DMSO and injected i.p., before the Pentylenetetrazol. Both JJKK048 and WWL70 revealed anticonvulsive effect. Anticonvulsive effect of JJKK048 but not WWL70 was CB1 receptor dependent. LY2183240 showed CB1 receptor dependent anticonvulsive effect. However, URB597 revealed a TRPV1 dependent proconvulsive effect. It seems extracellular accumulation of 2-AG or anandamide has anticonvulsive effect through the CB1 receptor, while intracellular anandamide accumulation is proconvulsive through TRPV1.

Aaltonen N, Savinainen JR, Ribas CR, Rönkkö J, Kuusisto A, Korhonen J, Navia-Paldanius D, Häyrinen J, Takabe P, Käsnänen H, Pantsar T, Laitinen T, Lehtonen M, Pasonen-Seppänen S, Poso A, Nevalainen T, Laitinen JT (2013) Piperazine and piperidine triazole ureas as ultrapotent and highly selective inhibitors of monoacylglycerol lipase. Chem Biol 20(3):379–390. https://doi.org/10.1016/j.chembiol.2013.01.012 CrossRefPubMed

Blair RE, Deshpande LS, Sombati S, Elphick MR, Martin BR, DeLorenzo RJ (2009) 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 57(3):208–218. https://doi.org/10.1016/j.neuropharm.2009.06.007 CrossRefPubMedPubMedCentral

Chavez AE, Chiu CQ, Castillo PE (2010) TRPV1 activation by endogenous anandamide triggers postsynaptic long-term depression in dentate gyrus. Nat Neurosci 13(12):1511–1518. https://doi.org/10.1038/nn.2684 CrossRefPubMedPubMedCentral

Chen W, Tang H, Liu H, Long L, Gong Z, Zheng J, Chi M, Xie Y, Zheng Z, Li S, Wang L (2010) Novel selective antagonist of the cannabinoid CB1 receptor, MJ15, with prominent anti-obesity effect in rodent models. Eur J Pharmacol 637(1-3):178–185. https://doi.org/10.1016/j.ejphar.2010.03.040 CrossRefPubMed

Citraro R, Russo E, Ngomba RT, Nicoletti F, Scicchitano F, Whalley BJ, Calignano A, de Sarro G (2013a) CB1 agonists, locally applied to the cortico-thalamic circuit of rats with genetic absence epilepsy, reduce epileptic manifestations. Epilepsy Res 106(1-2):74–82. https://doi.org/10.1016/j.eplepsyres.2013.06.004 CrossRefPubMed

Citraro R, Russo E, Scicchitano F, van Rijn CM, Cosco D, Avagliano C, Russo R, D'Agostino G, Petrosino S, Guida F, Gatta L, van Luijtelaar G, Maione S, di Marzo V, Calignano A, de Sarro G (2013b) Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-alpha receptor activation in a genetic model of absence epilepsy. Neuropharmacology 69:115–126. https://doi.org/10.1016/j.neuropharm.2012.11.017 CrossRefPubMed

Clement AB, Hawkins EG, Lichtman AH, Cravatt BF (2003) Increased seizure susceptibility and proconvulsant activity of anandamide in mice lacking fatty acid amide hydrolase. J Neurosci 23(9):3916–3923CrossRefPubMed

Cravatt BF, Giang DK, Mayfield SP, Boger DL, Lerner RA, Gilula NB (1996) Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 384(6604):83–87. https://doi.org/10.1038/384083a0 CrossRefPubMed

de Boer HM, Mula M, Sander JW (2008) The global burden and stigma of epilepsy. Epilepsy Behav 12(4):540–546. https://doi.org/10.1016/j.yebeh.2007.12.019 CrossRefPubMed

Deshpande LS, Blair RE, Ziobro JM, Sombati S, Martin BR, DeLorenzo RJ (2007) Endocannabinoids block status epilepticus in cultured hippocampal neurons. Eur J Pharmacol 558(1-3):52–59. https://doi.org/10.1016/j.ejphar.2006.11.030 CrossRefPubMed

Devinsky O, Cilio MR, Cross H, Fernandez-Ruiz J, French J, Hill C, Katz R, di Marzo V, Jutras-Aswad D, Notcutt WG, Martinez-Orgado J, Robson PJ, Rohrback BG, Thiele E, Whalley B, Friedman D (2014) Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia 55(6):791–802. https://doi.org/10.1111/epi.12631 CrossRefPubMedPubMedCentral

Di Marzo V (2008) Targeting the endocannabinoid system: to enhance or reduce? Nat Rev Drug Discov 7(5):438–455. https://doi.org/10.1038/nrd2553 CrossRefPubMed

Di Marzo V, Bifulco M, De Petrocellis L (2004) The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov 3(9):771–784. https://doi.org/10.1038/nrd1495 CrossRefPubMed

Fezza F, Marrone MC, Avvisati R, di Tommaso M, Lanuti M, Rapino C, Mercuri NB, Maccarrone M, Marinelli S (2014) Distinct modulation of the endocannabinoid system upon kainic acid-induced in vivo seizures and in vitro epileptiform bursting. Mol Cell Neurosci 62:1–9. https://doi.org/10.1016/j.mcn.2014.07.003 CrossRefPubMed

Gavva NR, Bannon AW, Surapaneni S, Hovland DN, Lehto SG, Gore A, Juan T, Deng H, Han B, Klionsky L, Kuang R, Le A, Tamir R, Wang J, Youngblood B, Zhu D, Norman MH, Magal E, Treanor JJS, Louis JC (2007) The vanilloid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation. J Neurosci 27(13):3366–3374. https://doi.org/10.1523/JNEUROSCI.4833-06.2007 CrossRefPubMed

Griebel G, Pichat P, Beeské S, Leroy T, Redon N, Jacquet A, Françon D, Bert L, Even L, Lopez-Grancha M, Tolstykh T, Sun F, Yu Q, Brittain S, Arlt H, He T, Zhang B, Wiederschain D, Bertrand T, Houtmann J, Rak A, Vallée F, Michot N, Augé F, Menet V, Bergis OE, George P, Avenet P, Mikol V, Didier M, Escoubet J (2015) Selective blockade of the hydrolysis of the endocannabinoid 2-arachidonoylglycerol impairs learning and memory performance while producing antinociceptive activity in rodents. Sci Rep 5(1):7642. https://doi.org/10.1038/srep07642 CrossRefPubMedPubMedCentral

Hill TD et al (2013) Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism. Br J Pharmacol 170(3):679–692. https://doi.org/10.1111/bph.12321 CrossRefPubMedPubMedCentral

Hoover HS, Blankman JL, Niessen S, Cravatt BF (2008) Selectivity of inhibitors of endocannabinoid biosynthesis evaluated by activity-based protein profiling. Bioorg Med Chem Lett 18(22):5838–5841. https://doi.org/10.1016/j.bmcl.2008.06.091 CrossRefPubMedPubMedCentral

Hsieh C, Brown S, Derleth C, Mackie K (1999) Internalization and recycling of the CB1 cannabinoid receptor. J Neurochem 73(2):493–501CrossRefPubMed

Karanian DA, Brown QB, Makriyannis A, Kosten TA, Bahr BA (2005) Dual modulation of endocannabinoid transport and fatty acid amide hydrolase protects against excitotoxicity. J Neurosci 25(34):7813–7820. https://doi.org/10.1523/JNEUROSCI.2347-05.2005 CrossRefPubMed

Kow RL, Jiang K, Naydenov AV, Le JH, Stella N, Nathanson NM (2014) Modulation of pilocarpine-induced seizures by cannabinoid receptor 1. PLoS One 9(4):e95922. https://doi.org/10.1371/journal.pone.0095922 CrossRefPubMedPubMedCentral

Ligresti A, Cascio MG, Di Marzo V (2005) Endocannabinoid metabolic pathways and enzymes. Curr Drug Targets CNS Neurol Disord 4(6):615–623. https://doi.org/10.2174/156800705774933104 CrossRefPubMed

Löscher W (2011) Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs. Seizure 20(5):359–368. https://doi.org/10.1016/j.seizure.2011.01.003 CrossRefPubMed

Ludanyi A et al (2011) Complementary synaptic distribution of enzymes responsible for synthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in the human hippocampus. Neuroscience 174:50–63. https://doi.org/10.1016/j.neuroscience.2010.10.062 CrossRefPubMed

Lutz B (2004) On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures. Biochem Pharmacol 68(9):1691–1698. https://doi.org/10.1016/j.bcp.2004.07.007 CrossRefPubMed

Ma L, Wang L, Yang F, Meng XD, Wu C, Ma H, Jiang W (2014) Disease-modifying effects of RHC80267 and JZL184 in a pilocarpine mouse model of temporal lobe epilepsy. CNS Neurosci Ther 20(10):905–915. https://doi.org/10.1111/cns.12302 CrossRefPubMed

Maione S, Morera E, Marabese I, Ligresti A, Luongo L, Ortar G, Di Marzo V (2008) Antinociceptive effects of tetrazole inhibitors of endocannabinoid inactivation: cannabinoid and non-cannabinoid receptor-mediated mechanisms. Br J Pharmacol 155(5):775–782. https://doi.org/10.1038/bjp.2008.308 CrossRefPubMedPubMedCentral

Marrs WR, Blankman JL, Horne EA, Thomazeau A, Lin YH, Coy J, Bodor AL, Muccioli GG, Hu SSJ, Woodruff G, Fung S, Lafourcade M, Alexander JP, Long JZ, Li W, Xu C, Möller T, Mackie K, Manzoni OJ, Cravatt BF, Stella N (2010) The serine hydrolase ABHD6 controls the accumulation and efficacy of 2-AG at cannabinoid receptors. Nat Neurosci 13(8):951–957. https://doi.org/10.1038/nn.2601 CrossRefPubMedPubMedCentral

Naydenov AV, Horne EA, Cheah CS, Swinney K, Hsu KL, Cao JK, Marrs WR, Blankman JL, Tu S, Cherry AE, Fung S, Wen A, Li W, Saporito MS, Selley DE, Cravatt BF, Oakley JC, Stella N (2014) ABHD6 blockade exerts antiepileptic activity in PTZ-induced seizures and in spontaneous seizures in R6/2 mice. Neuron 83(2):361–371. https://doi.org/10.1016/j.neuron.2014.06.030 CrossRefPubMedPubMedCentral

Pedroza-Llinas R, Mendez-Diaz M, Ruiz-Contreras AE, Prospero-Garcia O (2013) CB1 receptor activation in the nucleus accumbens core impairs contextual fear learning. Behav Brain Res 237:141–147. https://doi.org/10.1016/j.bbr.2012.09.032 CrossRefPubMed

Rock EM, Limebeer CL, Ward JM, Cohen A, Grove K, Niphakis MJ, Cravatt BF, Parker LA (2015) Interference with acute nausea and anticipatory nausea in rats by fatty acid amide hydrolase (FAAH) inhibition through a PPARalpha and CB1 receptor mechanism, respectively: a double dissociation. Psychopharmacology 232(20):3841–3848. https://doi.org/10.1007/s00213-015-4050-7 CrossRefPubMed

Ross RA (2003) Anandamide and vanilloid TRPV1 receptors. Br J Pharmacol 140(5):790–801. https://doi.org/10.1038/sj.bjp.0705467 CrossRefPubMedPubMedCentral

Rowley S, Sun X, Lima IV, Tavenier A, de Oliveira ACP, Dey SK, Danzer SC (2017) Cannabinoid receptor 1/2 double-knockout mice develop epilepsy. Epilepsia 58(12):e162–e166. https://doi.org/10.1111/epi.13930 CrossRefPubMed

Russo EB (2017) Cannabis and epilepsy: an ancient treatment returns to the fore. Epilepsy Behav 70(Pt B):292–297. https://doi.org/10.1016/j.yebeh.2016.09.040 CrossRefPubMed

Savinainen J, Saario S, Laitinen J (2012) The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2-arachidonoylglycerol signalling through cannabinoid receptors. Acta Physiol 204(2):267–276. https://doi.org/10.1111/j.1748-1716.2011.02280.x CrossRef

Schwenk J, Harmel N, Brechet A, Zolles G, Berkefeld H, Müller CS, Bildl W, Baehrens D, Hüber B, Kulik A, Klöcker N, Schulte U, Fakler B (2012) High-resolution proteomics unravel architecture and molecular diversity of native AMPA receptor complexes. Neuron 74(4):621–633. https://doi.org/10.1016/j.neuron.2012.03.034 CrossRefPubMed

Sheerin AH, Zhang X, Saucier DM, Corcoran ME (2004) Selective antiepileptic effects of N-palmitoylethanolamide, a putative endocannabinoid. Epilepsia 45(10):1184–1188. https://doi.org/10.1111/j.0013-9580.2004.16604.x CrossRefPubMed

Starowicz K, Makuch W, Korostynski M, Malek N, Slezak M, Zychowska M, Petrosino S, de Petrocellis L, Cristino L, Przewlocka B, di Marzo V (2013) Full inhibition of spinal FAAH leads to TRPV1-mediated analgesic effects in neuropathic rats and possible lipoxygenase-mediated remodeling of anandamide metabolism. PLoS One 8(4):e60040. https://doi.org/10.1371/journal.pone.0060040 CrossRefPubMedPubMedCentral

Sugaya Y, Yamazaki M, Uchigashima M, Kobayashi K, Watanabe M, Sakimura K, Kano M (2016) Crucial roles of the endocannabinoid 2-Arachidonoylglycerol in the suppression of epileptic seizures. Cell Rep 16(5):1405–1415. https://doi.org/10.1016/j.celrep.2016.06.083 CrossRefPubMed

VelÍŠKovÁ J (2006) CHAPTER 48 - behavioral characterization of seizures in rats A2 - Pitkänen, Asla. In: Schwartzkroin PA, Moshé SL (eds) Models of seizures and epilepsy. Academic, Burlington, pp 601–611. https://doi.org/10.1016/B978-012088554-1/50050-5 CrossRef

von Ruden EL, Bogdanovic RM, Wotjak CT, Potschka H (2015) Inhibition of monoacylglycerol lipase mediates a cannabinoid 1-receptor dependent delay of kindling progression in mice. Neurobiol Dis 77:238–245. https://doi.org/10.1016/j.nbd.2015.03.016 CrossRef

Wakley AA, Rasmussen EB (2009) Effects of cannabinoid drugs on the reinforcing properties of food in gestationally undernourished rats. Pharmacol Biochem Behav 94(1):30–36. https://doi.org/10.1016/j.pbb.2009.07.002 CrossRefPubMed

Wallace MJ, Martin BR, DeLorenzo RJ (2002) Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity. Eur J Pharmacol 452(3):295–301. https://doi.org/10.1016/S0014-2999(02)02331-2 CrossRefPubMed

Wen J, Ribeiro R, Tanaka M, Zhang Y (2015) Activation of CB2 receptor is required for the therapeutic effect of ABHD6 inhibition in experimental autoimmune encephalomyelitis. Neuropharmacology 99:196–209. https://doi.org/10.1016/j.neuropharm.2015.07.010 CrossRefPubMed

Title: Anticonvulsive effects of endocannabinoids; an investigation to determine the role of regulatory components of endocannabinoid metabolism in the Pentylenetetrazol induced tonic- clonic seizures
Authors: Parisa Zareie
Mehdi Sadegh
Mohammad Reza Palizvan
Homeira Moradi-Chameh
Publication date: 01-06-2018
Publisher: Springer US
Published in: Metabolic Brain Disease / Issue 3/2018
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-018-0195-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Anticonvulsive effects of endocannabinoids; an investigation to determine the role of regulatory components of endocannabinoid metabolism in the Pentylenetetrazol induced tonic- clonic seizures

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2018

Hibiscus rosa sinensis mediate anxiolytic effect via modulation of ionotropic GABA-A receptors: possible mechanism of action

Cardiovascular profile improvement during Natalizumab treatment

Oxidative stress in the brain caused by acute kidney injury

Association between PDE4D rs966221 polymorphism and risk of ischemic stroke: a systematic review and meta-analysis

Neonatal mitochondrial leukoencephalopathy with brain and spinal involvement and high lactate: expanding the phenotype of ISCA2 gene mutations

Turkish case of ethylmalonic encephalopathy misdiagnosed as short chain acyl-CoA dehydrogenase deficiency