INVESTIGATING THE SEROTONERGIC SYSTEM'S ROLE IN THE OCCURRENCE OF LITHIUM-PILOCARPINE-INDUCED SEIZURES

Main Article Content

Bahman Rabiei
Tahereh Sharifi

Keywords

Psychoactive drugs, Lithium-pilocarpine, Seizures, Serotonergic system

Abstract

The mechanism of lithium's psychoactive effects has not yet been clarified. However, the change in the endogenous chemical mediator systems of the brain is significant in the occurrence of its effects. Several interactions of lithium with muscarinic responses have been reported. In this regard, the mechanism enhancing convulsions induced by muscarinic agonists might be related to the mechanism of its psychoactive effects. It has been recommended that lithium might directly affect cholinergic neurotransmission or potentiate the effects of pilocarpine by affecting other chemical mediator systems. Owing to the significant role of the serotonergic system in the initiation, development, and suppression of seizures in various epilepsy models in this study, the present system investigates the occurrence of lithium-pilocarpine-induced seizures. The results suggest that pretreatment with some compounds affecting the serotonergic system such as cyproheptadine (0.2-0.8 mg/kg), propranolol (0.5-1 mg/kg), and fluoxetine (2-10 mg/kg) can suppress seizures induced by lithium-pilocarpine. However, destructing and even enhancing this system with para-chlorophenylalanine (150mg/kg) for three consecutive days before lithium), 5,7-Dihydroxytryptamine (200 µg per animal), and fenfluramine (55mg/kg) do not affect this type of seizure.

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References

1. Malhi GS, Outhred T, Morris G, Hamilton A, Das P, Mannie Z. Lithium in the treatment of mood disorders. Drugs. 2020;80(18):1855-1870.
2. Cipriani A, Hawton K, Stockton S, Geddes JR. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ. 2013;346:f3646.
3. Bauer M, Gitlin MJ. The essential guide to lithium treatment. Springer; 2016.
4. Geddes JR, Burgess S, Hawton K, Jamison K, Goodwin GM. Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials. Am J Psychiatry. 2004;161(2):217-222.
5. Belmaker RH, Agam G. Major depressive disorder. N Engl J Med. 2008;358(1):55-68.
6. Shorter E. The history of lithium therapy. Bipolar disorders. 2009 Jun;11:4-9.
7. Guo Y, He L, Xu Z. The potential therapeutic value of lithium in epilepsy and epileptic encephalopathies. Front Neurol. 2021;12:686486. doi:10.3389/fneur.2021.686486.
8. Shaheen M, Khalil H, Aref M, Salama N. Impact of lithium administration on seizures in individuals with epilepsy: A systematic review. Epilepsy Res. 2020;161:106276. doi:10.1016/j.eplepsyres.2020.106276.
9. Wang J, Li S, Cai J, Tao W, Xue Y. Safety and efficacy of lithium treatment for bipolar disorders comorbid with epilepsy: A systematic review. J Affect Disord. 2018;234:259-266. doi:10.1016/j.jad.2018.02.085.
10. Rajan TM, Menon V. Anticonvulsant properties of lithium: A comprehensive review. Prog Neuropsychopharmacol Biol Psychiatry. 2021;106:110104. doi:10.1016/j.pnpbp.2020.110104.
11. Smith D, Brown AS. Proconvulsive properties of lithium and its impact on EEG readings: A review. Seizure. 2018;60:59-64. doi:10.1016/j.seizure.2018.05.016.
12. Zhang Q, Wang X, Xu J, Xu X, He Q. Serotonergic modulation of epilepsy: Insights from serotonin receptor agonists and antagonists. Epilepsy Res. 2021;175:106689. doi:10.1016/j.eplepsyres.2021.106689.
13. Milan Aggarwal, Veena Puri, and Sanjeev Puri. 2012. Serotonin and CGRP in migraine. Annals of neurosciences 19, 2 (2012), 88.
14. Adriana Di Martino and Roberto F Tuchman. 2001. Antiepileptic drugs: affective use in autism spectrum disorders. Pediatric neurology 25, 3 (2001), 199–207.
15. PMP Ferreira, GCG Militão, and RM Freitas. 2009. Lipoic acid effects on lipid peroxidation level, superoxide dismutase activity and monoamines concentration in rat hippocampus. Neuroscience letters 464, 2 (2009), 131–13
16. Hamada Hamid and Andres M Kanner. 2013. Should antidepressant drugs of the selective serotonin reuptake inhibitor family be tested as antiepileptic drugs? Epilepsy & Behavior 26, 3 (2013), 261–265.
17. Dubravka Hranilović, Zorana Bujas-Petković, Maja Tomičić, Tatjana Bordukalo-Nikšić, Sofia Blažević, and Lipa Čičin Šain. 2009. Hyperserotonemia in autism: activity of 5HT-associated platelet proteins. Journal of Neural Transmission 116, (2009), 493–501.
18. Andres M Kanner. 2016. Most antidepressant drugs are safe for patients with epilepsy at therapeutic doses: a review of the evidence. Epilepsy & Behavior 61, (2016), 282–286.
19. Yohei Fujimoto, Tomoharu Funao, Koichi Suehiro, Ryota Takahashi, Takashi Mori, and Kiyonobu Nishikawa. 2015. Brain serotonin content regulates the manifestation of tramadol-induced seizures in rats: Disparity between tramadol-induced seizure and serotonin syndrome. Anesthesiology 122, 1 (2015), 178–189.
20. Arun Murugesan, MR Sandhya Rani, Johnson Hampson, Bilal Zonjy, Nuria Lacuey, Carl L Faingold, Daniel Friedman, Orrin Devinsky, Rup K Sainju, Stephan Schuele, and others. 2018. Serum serotonin levels in patients with epileptic seizures. Epilepsia 59, 6 (2018), e91–e97.
21. Arun Murugesan, MR Sandhya Rani, Laura Vilella, Nuria Lacuey, Johnson P Hampson, Carl L Faingold, Daniel Friedman, Orrin Devinsky, Rup K Sainju, Stephan Schuele, and others. 2019. Postictal serotonin levels are associated with peri-ictal apnea. Neurology 93, 15 (2019), e1485–e1494.
22. Faheem H Pottoo, Md Noushad Javed, Md Abul Barkat, Md Sabir Alam, Javaid Ashraf Nowshehri, Dhafer Mahdi Alshayban, and Mohammad Azam Ansari. 2019. Estrogen and serotonin: complexity of interactions and implications for epileptic seizures and epileptogenesis. Current Neuropharmacology 17, 3 (2019), 214–231.
23. Jacob Pade Ramsøe Jacobsen and Arne Mørk. 2004. The effect of escitalopram, desipramine, electroconvulsive seizures and lithium on brain-derived neurotrophic factor mRNA and protein expression in the rat brain and the correlation to 5-HT and 5-HIAA levels. Brain research 1024, 1–2 (2004), 183–192.
24. Kyohei Kin, Takao Yasuhara, Satoshi Kawauchi, Masahiro Kameda, Kakeru Hosomoto, Yousuke Tomita, Michiari Umakoshi, Ken Kuwahara, Ittetsu Kin, Naoya Kidani, and others. 2019. Lithium counteracts depressive behavior and augments the treatment effect of selective serotonin reuptake inhibitor in treatment-resistant depressed rats. Brain research 1717, (2019), 52–59.
25. Allison C Nugent, Paul J Carlson, Earle E Bain, William Eckelman, Peter Herscovitch, Husseini Manji, Carlos A Zarate Jr, and Wayne C Drevets. 2013. Mood stabilizer treatment increases serotonin type 1A receptor binding in bipolar depression. Journal of Psychopharmacology 27, 10 (2013), 894–902.
26. Ariane-Saskia Ries, Tim Hermanns, Burkhard Poeck, and Roland Strauss. 2017. Serotonin modulates a depression-like state in Drosophila responsive to lithium treatment. Nature communications 8, 1 (2017), 15738.
27. A Serretti, R Lilli, L Mandelli, C Lorenzi, and E Smeraldi. 2001. Serotonin transporter gene associated with lithium prophylaxis in mood disorders. The pharmacogenomics journal 1, 1 (2001), 71–77.
28. Yi Yang, Yi Guo, Yifang Kuang, Shan Wang, Yan Jiang, Yao Ding, Shuang Wang, and Meiping Ding. 2014. Serotonin 1A receptor inhibits the status epilepticus induced by lithium-pilocarpine in rats. Neuroscience bulletin 30, (2014), 401–408.
29. Francis Rodriguez Bambico, Andrea Duranti, Andrea Tontini, Giorgio Tarzia, Gabriella Gobbi, and others. 2009. Endocannabinoids in the treatment of mood disorders: evidence from animal models. Current Pharmaceutical Design 15, 14 (2009), 1623–46.
30. James Francescangeli, Kunal Karamchandani, Meghan Powell, and Anthony Bonavia. 2019. The serotonin syndrome: from molecular mechanisms to clinical practice. International journal of molecular sciences 20, 9 (2019), 2288.
31. Phillip C Jobe, John W Dailey, and Joe F Wernicke. 1999. A noradrenergic and serotonergic hypothesis of the linkage between epilepsy and affective disorders. Critical ReviewsTM in Neurobiology 13, 4 (1999).
32. Raymond Mongeau, P Blier, and C De Montigny. 1997. The serotonergic and noradrenergic systems of the hippocampus: their interactions and the effects of antidepressant treatments. Brain Research Reviews 23, 3 (1997), 145–195.
33. Katsumasa Muneoka, Yukihiko Shirayama, Morikuni Takigawa, and Seiji Shioda. 2009. Brain region-specific effects of short-term treatment with duloxetine, venlafaxine, milnacipran and sertraline on monoamine metabolism in rats. Neurochemical research 34, (2009), 542–555.
34. Roceanu, A.; Antochi, F.; Bajenaru, O. New Molecules in Migraine Treatment. Farmacia 2015, 63 (4), 475–481.
35. Kumar, M.; Kumar, P.; Koshal, P.; Jamwal, S. Neurochemical Imbalance in Epilepsy from Animal Model to Human. Current Psychopharmacology 2018, 7 (2), 113–128.
36. Monti, J. M. The Role of Dorsal Raphe Nucleus Serotonergic and Non-Serotonergic Neurons, and of Their Receptors, in Regulating Waking and Rapid Eye Movement (REM) Sleep. Sleep medicine reviews 2010, 14 (5), 319–327.
37. Waeber, C. Emerging Drugs in Migraine Treatment. Expert Opinion on Emerging Drugs 2003, 8 (2), 437–456
38. Annamneedi, A.; Gora, C.; Dudas, A.; Leray, X.; Bozon, V.; Crepieux, P.; Pellissier, L. P. Towards the Convergent Therapeutic Potential of GPCRs in Autism Spectrum Disorders. British Journal of Pharmacology 2022.
39. Predescu, D.-V.; Crețoiu, S. M.; Crețoiu, D.; Alexandra Pavelescu, L.; Suciu, N.; Radu, B. M.; Voinea, S.-C. G Protein-Coupled Receptors (GPCRs)-Mediated Calcium Signaling in Ovarian Cancer: Focus on GPCRs Activated by Neurotransmitters and Inflammation-Associated Molecules. International journal of molecular sciences 2019, 20 (22), 5568.
40. Poian, L. R.; Chiavegatto, S. Serotonin Syndrome: The Role of Pharmacology in Understanding Its Occurrence. Cureus 2023, 15 (5).
41. Trimble, M. R.; George, M. Biological Psychiatry; John Wiley & Sons, 2010.