Nukleus akumbens bölgesine uygulanan topiramatın morfin yoksunluk sendromu üzerine etkileri
Amaç: Bazal gangliyon çekirdeklerinden biri olan nukleus akumbens ve nörotransmitter olan dopamin opioid bağımlılığı ve yoksunluğunda kritik rol oynamaktadır. Opioid yoksunluğunda dopaminin yanı sıra glutamat ve GABA gibi nörotransmitterlerin de önemi bilinmektedir. Biz bu çalışmada morfin bağımlısı hayvanlarda GABAerjik ve glutamaterjik yolakları etkileyen antiepileptik ajan olan topiramatın nukleus akumbens bölgesine lokal uygulamasının naloksonla tetiklenen yoksunluk sendromunda yoksunluk bulguları ve lokomotor aktivite üzerine etkilerini araştırmayı amaçladık. Materyal ve Metot: Yirmi adet erkek Sprague-Dawley sıçanları topiramat tedavi grubu ve kontrol grubuna ayrıldı. Hayvanların hepsine morfin peletleri uygulandı, stereotaksik cerrahi işlemle nukleus akumbens bölgelerine kılavuz kanüller bilaretal yerleştirildi. Deneyin son gününde bilateral topiramat veya serum fizyolojik (kontrol grubu) mikroenjeksiyonlarını takiben nalokson uygulanarak morfin yoksunluğu tetiklendi. Bulgular: Nukleus akumbens bölgesine lokal uygulanan topiramat naloksonla tetiklenen morfin yoksunluk bulgularından sıçrama sayısını ve ağırlık kaybını anlamlı düzeyde baskıladı. Lokal topiramat uygulaması yoksunluk bulgularından ıslak köpek silkinmesinde ise anlamlı değişiklik yapmadı. Topiramat mikroenjeksiyonları stereotipik hareketleri artırdığı halde vertikal hareketler, ambulatuvar hareketler ve toplam kat edilen mesafe gibi lokomotor aktivite davranışlarını değiştirmedi. Sonuç: Bu bulgular antikonvülzan ilaç olan topiramatın nukleus akumbens bölgesine lokal enjeksiyonunun opioid yoksunluğunda etkili olduğunu, lokomotor aktivitede anlamı baskılanma yapmadan santral etkilerin yanı sıra periferik etkiler oluşturduğunu göstermektedir. Keywords: antikonvülzan; morfin; nukleus akumbens; sıçrama; ağırlık kaybı; lokomotor aktivite
The effects of topiramate applied to the nucleus accumbens region on morphine withdrawal syndrome
Abstract: Objective: Nucleus accumbens, one of the nuclei of the basal ganglia, and dopamine, the neurotransmitter play a critical role in opioid dependence and withdrawal. In opioid withdrawal, the importance of neurotransmitters such as glutamate and GABA, as well as dopamine, is known. In this study, we aimed to investigate the effects of local injections of topiramate, an antiepileptic agent affecting GABAergic and glutamatergic pathways, into the nucleus accumbens on withdrawal signs and locomotor activity during naloxone-induced withdrawal in morphine-dependent rats. Material and Method: Twenty male Sprague-Dawley rats were divided in topiramete treatment and control groups. All animals received morphine pellets and guide cannulas were placed bilaterally in the nucleus accumbens regions by stereotaxic surgery. On the last day of the experiment, following the bilateral topiramate or saline (control group) microinjections, morphine withdrawal was triggered by naloxone. Results: Topiramate microinjections into the nucleus accumbens region significantly suppressed the signs of naloxone-induced morphine withdrawal such as number of jumpings and weight loss. No significant difference was observed in wet dog shakes, one of the withdrawal signs, after local topiramate treatment. Although topiramate microinjections increased stereotypical activity it did not change locomotor activity behavior such as vertical and ambulatory activity, and total covered distance. Conclusion: These findings show that local microinjection of topiramate into the nucleus accumbens is effective in preventing opioid deprivation symptoms without significant leffect on locomotor activity.
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- Referans1
Mahluga Jafarova Demirkapu and Hasan Raci Yananli (February 27th 2020). Opium Alkaloids [Online First], IntechOpen, doi:10.5772/intechopen.91326. Available from: https://www.intechopen.com/online-first/opium-alkaloids.
Referans2
Koob GF. Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci. 1992;13(5):177-184.
Referans3
Gysling K, Wang RY. Morphine-induced activation of A10 dopamine neurons in the rat. Brain Res. 1983; 277(1):119-127.
Referans4
Diana M, Pistis M, Muntoni A, Gessa G. Profound decrease of mesolimbic dopaminergic neuronal activity in morphine withdrawn rats. J Pharmacol Exp Ther. 1995;272(2):781-785.
Referans5
Yananli H, Gören MZ, Berkman K, Aricioğlu F. Effect of agmatine on brain L-citrulline production during morphine withdrawal in rats: A microdialysis study in nucleus accumbens. Brain Research. 2007;1132:51-58. doi:10.1016/j.brainres.2006.11.028
Referans6
Topkara B, Yananli HR, Sakallı E, Demirkapu MJ. Effects of injection of gamma-aminobutyric acid agonists into the nucleus accumbens on naloxone induced morphine withdrawal. Pharmacology. 2017;100:131-138. doi:10.1159/000477548
Referans7
Demirkapu MJ, Yananlı HR, Kaleli M, Sakalli HE, Gören MZ, Topkara B. The role of adenosine A1 receptors in the nucleus accumbens during morphine withdrawal. Clinical nad Experimental Pharmacology and Physiology 2020 Apr;47(4):553-560. doi:10.1111/1440-1681.13224
Referans8
Maryanoff BE. Sugar sulfamates for seizure control: discovery and development of topiramate, a structurally unique antiepileptic drug. Curr Top Med Chem. 2009;9(11):1049-1062. doi:10.2174/156802609789630938.
Referans9
Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia. 2000;41 Suppl 1:S3-9.
Referans10
Wenzel RG, Schwarz K, Padiyara RS. Topiramate for migraine prevention. Pharmacotherapy. 2006 Mar;26(3):375-387. doi:10.1592/phco.26.3.375.
Referans11
Verrotti A, Scaparrotta A, Agostinelli S, Di Pillo S, Chiarelli F, Grosso S. Topiramate-induced weight loss: a review. Epilepsy Res. 2011;95(3):189-199. doi:10.1016/j.eplepsyres.2011.05.014.
Referans12
Arnone D. Review of the use of Topiramate for treatment of psychiatric disorders. Ann Gen Psychiatry. 2005;4(1):5. doi:10.1186/1744-859X-4-5.
Referans13
Garnett WR. Clinical pharmacology of topiramate: a review. Epilepsia. 2000;41 Suppl 1:S61-65.
Referans14
Chung JY, Kim MW, Kim M. Efficacy of zonisamide in migraineurs with nonresponse to topiramate. Biomed Res Int. 2014;2014:891348. doi:10.1155/2014/891348.
Referans15
Walker MC, Sander JW. Topiramate: a new antiepileptic drug for refractory epilepsy. Seizure. 1996;5(3):199-203.
Referans16
Zhang X, Velumian AA, Jones OT, Carlen PL. Modulation of high-voltage-activated calcium channels in dentate granule cells by topiramate. Epilepsia. 2000;41 Suppl 1:S52-60.
Referans17
Mula M, Cavanna AE, Monaco F: Psychopharmacology of topiramate: from epilepsy to bipolar disorder. Neuropsychiatr Dis Treat. 2006;2(4):475-488. doi:10.2147/nedt.2006.2.4.475.
Referans18
Maryanoff BE, McComsey DF, Costanzo MJ, Hochman C, Smith-Swintosky V, Shank RP. Comparison of sulfamate and sulfamide groups for the inhibition of carbonic anhydrase-II by using topiramate as a structural platform. J Med Chem. 2005;48(6):1941-1947.
Referans19
Dodgson SJ, Shank RP, Maryanoff BE. Topiramate as an inhibitor of carbonic anhydrase isoenzymes. Epilepsia. 2000;41 Suppl 1:S35-39. doi:10.1111/j.1528-1157.2000.tb06047.x.
Referans20
Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT. Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007;15(23):7229-7236.
Referans21
Hargreaves GA, McGregor IS. Topiramate moderately reduces the motivation to consume alcohol and has a marked antidepressant effect in rats. Alcohol Clin Exp Res. 2007;31(11):1900-1907.
Referans22
Zalewska-Kaszubska J, Bajer B, Gorska D, Andrzejczak D, Dyr W, Bieńkowski P. Effect of repeated treatment with topiramate on voluntary alcohol intake and beta-endorphin plasma level in Warsaw alcohol high-preferring rats. Psychopharmacology (Berl). 2013;225(2):275-281. doi:10.1007/s00213-012-2812-z.
Referans23
Cagetti E, Baicy KJ, Olsen RW. Topiramate attenuates withdrawal signs after chronic intermittent ethanol in rats. Neuroreport. 2004;15(1):207-210.
Referans24
Likhitsathian S, Uttawichai K, Booncharoen H, Wittayanookulluk A, Angkurawaranon C, Srisurapanont M. Topiramate treatment for alcoholic outpatients recently receiving residential treatment programs: a 12-week, randomized, placebo-controlled trial. Drug Alcohol Depend. 2013;133(2):440-446. doi:10.1016/j.drugalcdep.2013.06.032.
Referans25
Johnson BA, Rosenthal N, Capece JA, Wiegand F, Mao L, Beyers K, McKay A, Ait-Daoud N, Anton RF, Ciraulo DA, Kranzler HR, Mann K, O'Malley SS, Swift RM. Topiramate for Alcoholism Advisory Board; Topiramate for Alcoholism Study Group. Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA. 2007;298(14):1641-1651.
Referans26
Baltieri DA, Daró FR, Ribeiro PL, Andrade AG. Effects of topiramate or naltrexone on tobacco use among male alcohol-dependent outpatients. Drug Alcohol Depend. 2009;105(1-2):33-41. doi: 10.1016/j.drugalcdep.2009.05.025.
Referans27
Ma JZ, Johnson BA, Yu E, Weiss D, McSherry F, Saadvandi J, Iturriaga E, Ait-Daoud N, Rawson RA, Hrymoc M, Campbell J, Gorodetzky C, Haning W, Carlton B, Mawhinney J, Weis D, McCann M, Pham T, Stock C, Dickinson R, Elkashef A, Li MD. Fine-grain analysis of the treatment effect of topiramate on methamphetamine addiction with latent variable analysis. Drug Alcohol Depend. 2013;130(1-3):45-51. doi:10.1016/j.drugalcdep.2012.10.009.
Referans28
Kampman KM, Pettinati H, Lynch KG, Dackis C, Sparkman T, Weigley C, O'Brien CP. A pilot trial of topiramate for the treatment of cocaine dependence. Drug Alcohol Depend. 2004;75(3):233-240.
Referans29
Nuijten M, Blanken P, van den Brink W, Hendriks V. Treatment of crack-cocaine dependence with topiramate: a randomized controlled feasibility trial in The Netherlands. Drug Alcohol Depend. 2014;138:177-184. doi:10.1016/j.drugalcdep.2014.02.024.
Referans30
Echeverry-Alzate V, Giné E, Bühler KM, Calleja-Conde J, Olmos P, Gorriti MA, Nadal R, Rodríguez de Fonseca F, López-Moreno JA. Effects of topiramate on ethanol-cocaine interactions and DNA methyltransferase gene expression in the rat prefrontal cortex. Br J Pharmacol. 2014;171(12):3023-3036. doi:10.1111/bph.12636.
Referans31
Kampman KM, Pettinati HM, Lynch KG, Spratt K, Wierzbicki MR, O'Brien CP. A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence. Drug Alcohol Depend. 2013;133(1):94-99.doi:10.1016/j.drugalcdep.2013.05.026.
Referans32
Umbricht A, DeFulio A, Winstanley EL, Tompkins DA, Peirce J, Mintzer MZ, Strain EC, Bigelow GE. Topiramate for cocaine dependence during methadone maintenance treatment: a randomized controlled trial. Drug Alcohol Depend. 2014;140:92-100. doi:10.1016/j.drugalcdep.2014.03.033.
Referans33
Levin FR, Mariani JJ, Pavlicova M, Choi CJ, Mahony AL, Brooks DJ, Bisaga A, Dakwar E, Carpenter KM, Naqvi N, Nunes EV, Kampman K. Extended release mixed amphetamine salts and topiramate for cocaine dependence: A randomized clinical replication trial with frequent users. Drug Alcohol Depend. 2020;206:107700. doi:10.1016/j.drugalcdep.2019.107700.
Referans34
Medrano MC, Mendiguren A, Pineda J. Effect of ceftriaxone and topiramate treatments on naltrexone-precipitated morphine withdrawal and glutamate receptor desensitization in the rat locus coeruleus. Psychopharmacology (Berl). 2015;232(15):2795-2809. doi:10.1007/s00213-015-3913-2.
Referans35
Hajhashemi V, Abed-Natanzi M. Effect of five common anticonvulsant drugs on naloxone-precipitated morphine withdrawal in mice. Res Pharm Sci. 2011;6(1):57-62.
Referans36
Paxinos G, Watson C: The Rat Brain in Stereotaxic Coordinates (fourth edition).Academic press, San Diego, California, 1998.
Referans37
Bhargava I IN. Rapid induction and quantitation of morphine dependence in the rat by pellet implantation. Psychopharmacology 1977;52:55-62.
Referans38
Zarrindast MR, Habibi M, Borzabadi S, Fazli-Tabaei S, Hossein Yahyavi S, Rostamin P. The effects of dopamine receptor agents on naloxone-induced jumping behaviour in morphine-dependent mice. Eur J Pharmacol. 2002;451(3):287-293.
Referans39
Junqueira-Ayres DD, Asth L, Ayres AS, Lobão-Soares B, Soares-Rachetti VP, Gavioli EC. Topiramate reduces basal anxiety and relieves ethanol withdrawal-induced anxious behaviors in male rats. Exp Clin Psychopharmacol. 2017;25(2):105-113. doi:10.1037/pha0000118.
Referans40
Sepúlveda J, Astorga JG, Contreras E. Riluzole decreases the abstinence syndrome and physical dependence in morphine-dependent mice. Eur J Pharmacol. 1999;379(1):59-62.
Referans41
Zullino DF, Cottier AC, Besson J. Topiramate in opiate withdrawal. Prog Neuropsychopharmacol Biol Psychiatry. 2002 Oct;26(6):1221-1223.
Referans42
Gracy KN, Pickel VM Ultrastructural immunocytochemical localization of the N-methyl-D-aspartate receptor and tyrosine hydroxylase in the shell of the rat nucleus accumbens. Brain Res. 1996 Nov 01, 739(1-2):169-181.
Referans43
Tarazi FI, Campbell A, Yeghiayan SK, Baldessarini RJ. Localization of ionotropic glutamate receptors in caudate-putamen and nucleus accumbenssepti of rat brain: comparison of NMDA, AMPA, and kainate receptors. Synapse. 1998; 30(2): 227-235.
Referans44
Conrad KL, Tseng KY, Uejima JL, et al. Formation of accumbens GluR2- lacking AMPA receptors mediates incubation of cocaine craving. Nature. 2008;454(7200):118–121.
Referans45
McCutcheon JE, Wang X, Tseng KY, Wolf ME, Marinelli M. Calciumpermeable AMPA receptors are present in nucleus accumbens synapses after prolonged withdrawal from cocaine self-administration but not experimenter-administered cocaine. J Neurosci. 2011;31(15): 5737–5743.
Referans46
McLemore GL, Kest B, Inturrisi CE. The effects of LY293558, an AMPA receptor antagonist, on acute and chronic morphine dependence. Brain Res. 1997;778(1):120-126.
Referans47
Ostadhadi S, Khan MI, Norouzi-Javidan A, Chamanara M, Jazaeri F, Zolfaghari S, Dehpour AR. Involvement of NMDA receptors and L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effects of topiramate in mice forced swimming test. Brain Res Bull. 2016 Apr;122:62-70. doi:10.1016/j.brainresbull.2016.03.004.
Referans48
Jasinski DR, Johnson RE, Kocher TR. Clonidine in morphine withdrawal. Differential effects on signs and symptoms. Arch Gen Psychiatry. 1985;42(11):1063-1066.
Referans49
Pappagallo M. Incidence, prevalence, and management of opioid bowel dysfunction. Am J Surg. 2001;182(5A Suppl):11S-18S. doi:10.1016/s0002-9610(01)00782-6.
Referans50
Meissner W, Schmidt U, Hartmann M, et al. Oral naloxone reverses opioid-associated constipation. Pain 2000;84:105–109.
Referans51
Fisher D, Grap MJ, Younger JB, Ameringer S, Elswick RK. Opioid withdrawal signs and symptoms in children: frequency and determinants. Heart Lung. 2013;42(6):407-13. doi:10.1016/j.hrtlng.2013.07.008.
Referans52
Adams RE, Wooten GF. Dependence and withdrawal following intracerebroventricular and systemic morphine administration: functional anatomy and behavior. Brain Res. 1990;518(1-2):6-10.
Referans53
Garner JP, Mason GJ. Evidence for a relationship between cage stereotypies and behavioural disinhibition in laboratory rodents. Behav Brain Res. 2002 17;136(1):83-92. doi:10.1016/s0166-4328(02)00111-0.
Referans54
Pappas SS, Leventhal DK, Albin RL, Dauer WT. Mouse models of neurodevelopmental disease of the basal ganglia and associated circuits. Curr Top Dev Biol. 2014;109:97-169. doi:10.1016/B978-0-12-397920-9.00001-9.
Referans55
Druhan JP, Walters CL, Aston-Jones G. Behavioral activation induced by D(2)-like receptor stimulation during opiate withdrawal. J Pharmacol Exp Ther. 2000;294(2):531-538.
Referans56
Lee JM, DeLeon-Jones F, Fields JZ, Ritzmann RF. Cyclo (Leu-Gly) attenuates the striatal dopaminergic supersensitivity induced by chronic morphine. Alcohol Drug Res. 1987;7(1):1-10.
Referans57
Hamlin AS, McNally GP, Westbrook RF, Osborne PB. Induction of Fos proteins in regions of the nucleus accumbens and ventrolateral striatum correlates with catalepsy and stereotypic behaviours induced by morphine. Neuropharmacology. 2009 Mar;56(4):798-807.