ANTIDEPRESSANT SCREENING OF LITHIUM CARBONATE IN THE PRESENCE OF PHENYTOIN USING A FORCED SWIMMING MAZE IN ALBINO MICE

Keywords

Antidepressant
Forced swimming maze
Interaction
Lithium carbonate
Phenytoin

How to Cite

aburawi, suhera, Saad, S., & ALgrabli, A. (2024). ANTIDEPRESSANT SCREENING OF LITHIUM CARBONATE IN THE PRESENCE OF PHENYTOIN USING A FORCED SWIMMING MAZE IN ALBINO MICE. Journal of Research in Pharmacy and Pharmaceutical Sciences, 3(1), 1–25. https://doi.org/10.33533/jrpps.v3i1.7925

Abstract

Lithium was introduced into modern psychiatric medicine; in 1970, Lithium was approved by the Food and Drug Administration for the treatment of manic illness; later in 1974 is used for the prevention of manic-depressive illness.  Aim of the study: To find out the effect of lithium on mental depression in the presence of phenytoin as a sodium channel blocker, using mice Methods: Male albino mice weighing between 25-40g are used. A forced swimming maze is used to screen for the effect of Lithium on mental depression. Drugs subacute administration is applied. Results: Lithium or phenytoin administration, each alone produces an antidepressant effect. While subacute administration of combined treatment of lithium and phenytoin produces an antidepressant effect less than the additive action of both lithium and phenytoin. Conclusion: Lithium has an antidepressant effect; also, phenytoin administration produces antidepressant action. Administration of phenytoin and lithium together, leads to a decrease in the pharmacological effect of each, as antidepressant, due to their interaction. Therefore, patients receiving the combined treatment of phenytoin and lithium should be under observation. Also, the free (unbound) phenytoin and lithium levels should be measured under medical control. 

https://doi.org/10.33533/jrpps.v3i1.7925

References

Abdelsayed, M. & Sokolov, S. (2013) Voltage-gated sodium channels: Pharmaceutical targets via anticonvulsants to treat epileptic syndromes. Channels, 7, 146–152. DOI: 10.4161/chan.24380, PubMed: 23531742.

Abdul, M. & Hoosein, N. (2001) Inhibition by anticonvulsants of prostate-specific antigen and interleukin-6 secretion by human prostate cancer cells. Anticancer Research, 21, 2045–2048. PubMed: 11497296.

Abraham, M. (2020) Risks and benefits of taking lithium for anxiety. Checked by faiq Shaikh, and Micah Abraham. last updated 10 October, 2020 https://www.calmclinic.com/anxiety-treatments/lithium.

Aburawi, S.M. & Baayo, S.A. (2017) Behavior effect of fluoxetine in presence of selenium using albino mice. International Journal of Pharmacology, Phytochemistry and Ethnomedicine, 7, 1–8. DOI: 10.18052/www.scipress.com/IJPPE.7.1.

Adan-Manes, J., Novalbos, J., López-Rodríguez, R., Ayuso-Mateos, J.L. & Abad-Santos, F. (2006) Lithium and venlafaxine interaction: A case of serotonin syndrome. Journal of Clinical Pharmacy and Therapeutics, 31, 397–400. DOI: 10.1111/j.1365-2710.2006.00745.x, PubMed: 16882112.

Ahmad, M., Wolberg, A. & Kahwaji, C.I. (updated 2022) Biochemistry, electron transport chain. StatPearls [Internet]. In: StatPearls Publishing: Treasure Island, (FL), USA, p. 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526105/.

Ahmad, S., Fowler, L.J. & Whitton, P.S. (2005) Lamotrigine, carbamazepine, and phenytoin differentially alter extracellular levels of 5-hydroxytryptamine, dopamine, and amino acids. Epilepsy Research, 63, 141–149. DOI: 10.1016/j.eplepsyres.2005.02.002, PubMed: 15777732.

Albert, P.R. & Blier, P. (2023) Does serotonin matter in depression? Journal of Psychiatry and Neuroscience, 48, E400–E403. DOI: 10.1503/jpn.230130, PubMed: 37857415.

Alda, M. (2015) Lithium in the treatment of bipolar disorder: Pharmacology and pharmacogenetics. Molecular Psychiatry, 20, 661–670. DOI: 10.1038/mp.2015.4, PubMed: 25687772.

Allagui, M.S., Nciri, R., Rouhaud, M.F., Murat, J.C., El Feki, A., Croute, F. & Vincent, C. (2009) Long-term exposure to low lithium concentrations stimulates proliferation, modifies stress protein expression patterns, and enhances resistance to oxidative stress in SH-SY5Y cells. Neurochemical Research, 34, 453–462. DOI: 10.1007/s11064-008-9804-8, PubMed: 18688712.

The American Soc. of Health System Pharmacists Lithium salts. Archived from the Original on 8 December 2015. Retrieved 1 December 2015.

Arraf, Z., Amit, T., Youdim, M.B.H. & Farah, R. (2012) Lithium and oxidative stress lessons from the MPTP model of Parkinson’s disease. Neuroscience Letters, 516, 57–61. DOI: 10.1016/j.neulet.2012.03.055, PubMed: 22480690.

Asconapé, J.J. (2014) Use of antiepileptic drugs in hepatic and renal disease. Handbook of Clinical Neurology, 119, 417–432. DOI: 10.1016/B978-0-7020-4086-3.00027-8, PubMed: 24365310.

Aylmer, C.G., Steinberg, H. & Webster, R.A. (1987) Hyperactivity induced by dexamphetamine/chlordiazepoxide mixtures in rats and its attenuation by lithium pretreatment: A role for dopamine? Psychopharmacology, 91, 198–206. DOI: 10.1007/BF00217062, PubMed: 3107031.

Aznar, S., Klein, A.B., Santini, M.A., Knudsen, G.M., Henn, F., Gass, P. & Vollmayr, B. (2010) Aging and depression vulnerability interaction results in decreased serotonin innervation associated with reduced BDNF levels in the hippocampus of rats bred for learned helplessness. Synapse, 64, 561–565. DOI: 10.1002/syn.20773, PubMed: 20222154.

Bachmann, R.F., Wang, Y., Yuan, P., Zhou, R., Li, X., Alesci, S., Du, J. & Manji, H.K. (2009) Common effects of lithium and valproate on mitochondrial functions: Protection against methamphetamine-induced mitochondrial damage. International Journal of Neuropsychopharmacology, 12, 805–822. DOI: 10.1017/S1461145708009802, PubMed: 19149911.

Bagdy, G., Kecskemeti, V., Riba, P. & Jakus, R. (2007) Serotonin and epilepsy [Review]. Journal of Neurochemistry, 100, 857–873. DOI: 10.1111/j.1471-4159.2006.04277.x, PubMed: 17212700.

Bahremand, A., Nasrabady, S.E., Ziai, P., Rahimian, R., Hedayat, T., Payandemehr, B. & Dehpour, A.R. (2010) Involvement of nitric oxide-cGMP pathway in the anticonvulsant effects of lithium chloride on PTZ-induced seizure in mice. Epilepsy Research, 89, 295–302. DOI: 10.1016/j.eplepsyres.2010.02.001, PubMed: 20304610.

Bai, F., Bergeron, M. & Nelson, D.L. (2003) Chronic AMPA receptor potentiator (LY451646) treatment increases cell proliferation in adult rat hippocampus. Neuropharmacology, 44, 1013–1021. DOI: 10.1016/s0028-3908(03)00104-7, PubMed: 12763094.

Ballou, L.M., Tian, P.Y., Lin, H.Y., Jiang, Y.P. & Lin, R.Z. (2001) Dual regulation of glycogen synthase kinase-3beta by the alpha1A-adrenergic receptor. Journal of Biological Chemistry, 276, 40910–40916. DOI: 10.1074/jbc.M103480200, PubMed: 11533051.

Barnes, J.C., Costall, B., Domeney, A.M. & Naylor, R.J. (1986) Lithium and bupropion antagonize the phasic changes in locomotor activity caused by dopamine infused into the rat nucleus accumbens. Psychopharmacology, 89, 311–316. DOI: 10.1007/BF00174366, PubMed: 3088656.

Bauer, M., Adli, M., Ricken, R., Severus, E. & Pilhatsch, M. (2014) Role of lithium augmentation in the management of major depressive disorder. CNS Drugs, 28, 331–342. DOI: 10.1007/s40263-014-0152-8, PubMed: 24590663.

Bauer, M. & Gitlin, M. (2016) Treatment of depression with lithium. The Essential Guide to Lithium Treatment. Springer International Publishing: Cham, Germany, pp. 71–80. DOI: 10.1007/978-3-319-31214-9_7.

Beaulieu, J.M. (2012) A role for Akt and glycogen synthase kinase-3 as integrators of dopamine and serotonin neurotransmission in mental health. Journal of Psychiatry and Neuroscience, 37, 7–16. DOI: 10.1503/jpn.110011, PubMed: 21711983.

Beaulieu, J.M., Sotnikova, T.D., Yao, W.D., Kockeritz, L., Woodgett, J.R., Gainetdinov, R.R. & Caron, M.G. (2004) Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Proceedings of the National Academy of Sciences of the United States of America, 101, 5099–5104. DOI: 10.1073/pnas.0307921101, PubMed: 15044694.

Black, J., Hannaman, T. & Malone, C. (1987) The relationship of serum albumin level to phenytoin toxicity. Journal of Clinical Pharmacology, 27, 249–250. DOI: 10.1002/j.1552-4604.1987.tb02194.x, PubMed: 3680582.

Bond, D.J., Andreazza, A.C., Hughes, J., Dhanoa, T., Torres, I.J., Kozicky, J.M., Young, L.T., Lam, R.W. & Yatham, L.N. (2016) Association of peripheral inflammation with body mass index and depressive relapse in bipolar disorder. Psychoneuroendocrinology, 65, 76–83. DOI: 10.1016/j.psyneuen.2015.12.012, PubMed: 26731572.

Bonnycastle, D.D., Giarman, N.J. & Paasonen, M.K. (1957) Anticonvulsant compounds and 5-hydroxytryptamine in rat brain. British Journal of Pharmacology and Chemotherapy, 12, 228–231. DOI: 10.1111/j.1476-5381.1957.tb00125.x, PubMed: 13446378.

Borsini, F. (1995) Role of the serotonergic system in the forced swimming test. Neuroscience and Biobehavioral Reviews, 19, 377–395. DOI: 10.1016/0149-7634(94)00050-b, PubMed: 7566740.

Bourin, M., Chenu, F. & Hascoët, M. (2009) The role of sodium channels in the mechanism of action of antidepressants and mood stabilizers. Current Drug Targets, 10, 1052–1060. DOI: 10.2174/138945009789735138, PubMed: 19702557.

Brady, R.O., Jr, McCarthy, J.M., Prescot, A.P., Jensen, J.E., Cooper, A.J., Cohen, B.M., Renshaw, P.F. & Ongür, D. (2013) Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder. Bipolar Disorders, 15, 434–439. DOI: 10.1111/bdi.12074, PubMed: 23634979.

Brietzke, E., Stertz, L., Fernandes, B.S., Kauer-Sant’Anna, M., Mascarenhas, M., Escosteguy Vargas, A., Chies, J.A. & Kapczinski, F. (2009) Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder. Journal of Affective Disorders, 116, 214–217. DOI: 10.1016/j.jad.2008.12.001, PubMed: 19251324.

Brunello, N. & Tascedda, F. (2003) Cellular mechanisms and second messengers: Relevance to the psychopharmacology of bipolar disorders. International Journal of Neuropsychopharmacology, 6, 181–189. DOI: 10.1017/S1461145703003419, PubMed: 12890311.

Brunton, L., Chabner, B. & Knollman, B. (2011). Goodman and Gilman’s the Pharmacological Basis of Therapeutics, 12th edn [Internet]. McGraw-Hill Professional: New York, USA. Available from: books.google.com/books/about/Goodman_and_Gilman_s_The_Pharmacological.html?id=e_yAOpyyaowC&pgis=1. cited 17 December 2014.

Cade, J.F. (1949a) Lithium salts in the treatment of psychotic excitement. Medical Journal of Australia, 2, 349–352. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2560740/pdf/10885180.pdf. DOI: 10.1080/j.1440-1614.1999.06241.x, PubMed: 18142718.

Cade, J.F. (2000) Lithium salts in the treatment of psychotic excitement. 1949. Bulletin of the World Health Organization, 78, 518–520, PubMed: 10885180.

Cantrell, A.R., Scheuer, T. & Catterall, W.A. (1999) Voltage-dependent neuromodulation of Na+ channels by D1-like dopamine receptors in rat hippocampal neurons. Journal of Neuroscience, 19, 5301–5310. DOI: 10.1523/JNEUROSCI.19-13-05301.1999, PubMed: 10377341.

Chalecka-Franaszek, E. & Chuang, D.M. (1999) Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. Proceedings of the National Academy of Sciences of the United States of America, 96, 8745–8750. DOI: 10.1073/pnas.96.15.8745, PubMed: 10411946.

Chen, Y., Yu, F.H., Sharp, E.M., Beacham, D., Scheuer, T. & Catterall, W.A. (2008) Functional properties and differential neuromodulation of Na(v)1.6 channels. Molecular and Cellular Neurosciences, 38, 607–615. DOI: 10.1016/j.mcn.2008.05.009, PubMed: 18599309.

Chiu, C.T. & Chuang, D.M. (2010) Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders. Pharmacology and Therapeutics, 128, 281–304. DOI: 10.1016/j.pharmthera.2010.07.006, PubMed: 20705090.

Chourbaji, S., Zacher, C., Sanchis-Segura, C., Dormann, C., Vollmayr, B. & Gass, P. (2005) Learned helplessness: Validity and reliability of depressive-like states in mice. Brain Research. Brain Research Protocols, 16, 70–78. DOI: 10.1016/j.brainresprot.2005.09.002, PubMed: 16338640.

Clarke, W.B., Clarke, R.M., Olson, E.K., Barr, R.D. & Downing, R.G. (1998) Binding of lithium and boron to human plasma proteins. Biological Trace Element Research, 65, 237–249. DOI: 10.1007/BF02789099, PubMed: 9892496.

Clarke, W.B., Guscott, R. & Lindstrom, R.M. (2004) Binding of lithium and boron to human plasma proteins II: Results for a bipolar not on lithium therapy. Biological Trace Element Research, 97 Accessed 18 December, 2023, 117–124. DOI: 10.1385/BTER:97:2:117, PubMed: 14985622.

Corena-McLeod, M., Walss-Bass, C., Oliveros, A., Gordillo Villegas, A., Ceballos, C., Charlesworth, C.M., Madden, B., Linser, P.J., Van Ekeris, L., Smith, K. & Richelson, E. (2013) New model of action for mood stabilizers: Phosphoproteome from rat pre-frontal cortex synaptoneurosomal preparations. PLOS ONE, 8, e52147. DOI: 10.1371/journal.pone.0052147, PubMed: 23690912.

Cossenza, M., Socodato, R., Portugal, C.C., Domith, I.C.L., Gladulich, L.F.H., Encarnação, T.G., Calaza, K.C., Mendonça, H.R., Campello-Costa, P. & Paes-de-Carvalho, R. (2014) Nitric oxide in the nervous system: Biochemical, developmental, and neurobiological aspects. Vitamins and Hormones, 96, 79–125. DOI: 10.1016/B978-0-12-800254-4.00005-2, PubMed: 25189385.

Crossley, N.A. & Bauer, M. (2007) Acceleration and augmentation of antidepressants with lithium for depressive disorders: Two meta-analyses of randomized, placebo-controlled trials. Journal of Clinical Psychiatry, 68, 935–940. DOI: 10.4088/jcp.v68n0617, PubMed: 17592920.

Cryan, J.F., Markou, A. & Lucki, I. (2002) Assessing antidepressant activity in rodents: Recent developments and future needs. Trends in Pharmacological Sciences, 23, 238–245. DOI: 10.1016/s0165-6147(02)02017-5, PubMed: 12008002.

Cui, J., Shao, L., Young, L.T. & Wang, J.F. (2007) Role of glutathione in neuroprotective effects of mood stabilizing drugs lithium and valproate. Neuroscience, 144, 1447–1453. DOI: 10.1016/j.neuroscience.2006.11.010, PubMed: 17184924.

De Sarno, P., Li, X. & Jope, R.S. (2002) Regulation of Akt and glycogen synthase kinase-3 beta phosphorylation by sodium valproate and lithium. Neuropharmacology, 43, 1158–1164. DOI: 10.1016/s0028-3908(02)00215-0, PubMed: 12504922.

de Vasconcellos, A.P.S., Nieto, F.B., Crema, L.M., Diehl, L.A., de Almeida, L.M., Prediger, M.E., da Rocha, E.R. & Dalmaz, C. (2006) Chronic lithium treatment has antioxidant properties but does not prevent oxidative damage induced by chronic variate stress. Neurochemical Research, 31, 1141–1151. DOI: 10.1007/s11064-006-9139-2, PubMed: 16944317.

DeLoye, S. (2023) Search for a major depression trigger reveals a familiar face: Discovery opens new possibilities for treatments. UFHealth. https://ufhealth.org/news/2023/search-major-depression-trigger-reveals-familiar-face-discovery-opens-new-possibilities#for-the-media.

Diniz, B.S., Talib, L.L., Joaquim, H.P.G., de Paula, V.R.J., Gattaz, W.F. & Forlenza, O.V. (2011) Platelet GSK3B activity in patients with late-life depression: Marker of depressive episode severity and cognitive impairment? World Journal of Biological Psychiatry, 12, 216–222. DOI: 10.3109/15622975.2010.551408, PubMed: 21314327.

Drugs.com (2023) Phenytoin for anxiety user reviews. https://www.drugs.com/comments/phenytoin/for-anxiety.html. 19 March, 2023.

Duda, P., Hajka, D., Wójcicka, O., Rakus, D. & Gizak, A. (2020) GSK3β: A master player in depressive disorder pathogenesis and treatment responsiveness. Cells, 9, 727. DOI: 10.3390/cells9030727, PubMed: 32188010.

Ercis, M., Ozerdem, A. & Singh, B. (2023) When and how to use lithium augmentation for treating major depressive disorder. Journal of Clinical Psychiatry, 84:23ac14813. DOI: 10.4088/JCP.23ac14813, PubMed: 36883886.

Eugene, A.R., Masiak, J., Masiak, M. & Kapica, J. (2014) Isolating the norepinephrine pathway comparing lithium in bipolar patients to SSRIs in depressive patients. Brain (Bacau), 5, 5–15. PubMed: 26609422.

Farber, N.B., Jiang, X.P., Heinkel, C. & Nemmers, B. (2002) Antiepileptic drugs and agents that inhibit voltage-gated sodium channels prevent NMDA antagonist neurotoxicity. Molecular Psychiatry, 7, 726–733. DOI: 10.1038/sj.mp.4001087, PubMed: 12192617.

Fasipe, O.J., Agede, O.A. & Enikuomehin, A.C. (2020) Announcing the novel class of GABA-A receptor selective positive allosteric modulator antidepressants. Future Science OA, 7, FSO654. DOI: 10.2144/fsoa-2020-0108, PubMed: 33437518.

Faturachman, G.F., Sari, L.T., Artanti, N., Shakira, S. & Zalikha, T.N. (2022) Phenytoin: Clinical use, pharmacokinetics, pharmacodynamics, toxicology, side effects, contraindication, and drug interactions review. Journal of Science and Technology Research for Pharmacy, 2, 31–37. DOI: 10.15294/jstrp.v2i2.69275.

Flemenbaum, A. (1977) Lithium inhibition of norepinephrine and dopamine receptors. Biological Psychiatry, 12, 563–572. https://pubmed.ncbi.nlm.nih.gov/560884/. PubMed: 560884.

Frey, B.N., Andreazza, A.C., Kunz, M., Gomes, F.A., Quevedo, J., Salvador, M., Gonçalves, C.A. & Kapczinski, F. (2007) Increased oxidative stress and DNA damage in bipolar disorder: A twin-case report. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 31, 283–285. DOI: 10.1016/j.pnpbp.2006.06.011, PubMed: 16859818.

Gerner, R.H., Fairbanks, L., Anderson, G.M., Young, J.G., Scheinin, M., Linnoila, M., Hare, T.A., Shaywitz, B.A. & Cohen, D.J. (1984) CSF neurochemistry in depressed, manic, and schizophrenic patients compared with that of normal controls. American Journal of Psychiatry, 141, 1533–1540. DOI: 10.1176/ajp.141.12.1533, PubMed: 6209989.

Ghasemi, M., Raza, M. & Dehpour, A.R. (2010) NMDA receptor antagonists augment antidepressant-like effects of lithium in the mouse forced swimming test. Journal of Psychopharmacology, 24, 585–594. DOI: 10.1177/0269881109104845, PubMed: 19351802.

Ghasemi, M., Sadeghipour, H., Mosleh, A., Sadeghipour, H.R., Mani, A.R. & Dehpour, A.R. (2008) Nitric oxide involvement in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test. European Neuropsychopharmacology, 18, 323–332. DOI: 10.1016/j.euroneuro.2007.07.011, PubMed: 17728109.

Ghasemi, M., Sadeghipour, H., Poorheidari, G. & Dehpour, A.R. (2009) A role for nitrergic system in the antidepressant-like effects of chronic lithium treatment in the mouse forced swimming test. Behavioural Brain Research, 200, 76–82. DOI: 10.1016/j.bbr.2008.12.032, PubMed: 19166880.

Gitlin, M. (2016) Lithium side effects and toxicity: Prevalence and management strategies. International Journal of Bipolar Disorders, 4, 27. DOI: 10.1186/s40345-016-0068-y, PubMed: 27900734.

Goldstein, B.I., Kemp, D.E., Soczynska, J.K. & McIntyre, R.S. (2009) Inflammation and the phenomenology, pathophysiology, comorbidity, and treatment of bipolar disorder: A systematic review of the literature. Journal of Clinical Psychiatry, 70, 1078–1090. DOI: 10.4088/JCP.08r04505, PubMed: 19497250.

Gould, T.D., Einat, H., Bhat, R. & Manji, H.K. (2004) AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. International Journal of Neuropsychopharmacology, 7, 387–390. DOI: 10.1017/S1461145704004535, PubMed: 15315719.

Gould, T.D., O’Donnell, K.C., Dow, E.R., Du, J., Chen, G. & Manji, H.K. (2008) Involvement of AMPA receptors in the antidepressant-like effects of lithium in the mouse tail suspension test and forced swim test. Neuropharmacology, 54, 577–587. DOI: 10.1016/j.neuropharm.2007.11.002, PubMed: 18096191.

Grace, A.A. (2016) Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression. Nature Reviews. Neuroscience, 17, 524–532. DOI: 10.1038/nrn.2016.57, PubMed: 27256556.

Griffith, W.H. & Taylor, L. (1988) Phenytoin reduces excitatory synaptic transmission and post-tetanic potentiation in the in vitro hippocampus. Journal of Pharmacology and Experimental Therapeutics, 246, 851–858. PubMed: 2843632.

Guo, C., Sun, L., Chen, X. & Zhang, D. (2013) Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regeneration Research, 8, 2003–2014. DOI: 10.3969/j.issn.1673-5374.2013.21.009, PubMed: 25206509.

Guzman, F. (2016) Lithium’s mechanism of action: An illustrated review. Published: 11/13/2016. https://psychopharmacologyinstitute.com/publication/lithiums-mechanism-of-action-an-illustrated-review-2212.

Hains, B.C., Saab, C.Y., Lo, A.C. & Waxman, S.G. (2004) Sodium channel blockade with phenytoin protects spinal cord axons, enhances axonal conduction, and improves functional motor recovery after contusion SCI. Experimental Neurology, 188, 365–377. DOI: 10.1016/j.expneurol.2004.04.001, PubMed: 15246836.

Hains, B.C. & Waxman, S.G. (2005) Neuroprotection by sodium channel blockade with phenytoin in an experimental model of glaucoma. Investigative Ophthalmology and Visual Science, 46, 4164–4169. DOI: 10.1167/iovs.05-0618, PubMed: 16249495.

Hamdani, N., Doukhan, R., Kurtlucan, O., Tamouza, R. & Leboyer, M. (2013) Immunity, inflammation, and bipolar disorder: Diagnostic and therapeutic implications. Current Psychiatry Reports, 15, 387. DOI: 10.1007/s11920-013-0387-y, PubMed: 23955004.

Hansen, J.M., Plowman, C.J. & Piorczynski, T.B. (2018) Developmental toxicity of antiepileptic drugs—An update. Comprehensive Toxicology, 5, 168–178. Publisher: ScienceDirect. DOI: 10.1016/B978-0-08-046884-6.01518-9.

Harkin, A.J., Bruce, K.H., Craft, B. & Paul, I.A. (1999) Nitric oxide synthase inhibitors have antidepressant-like properties in mice. 1. Acute treatments are active in the forced swim test. European Journal of Pharmacology, 372, 207–213. DOI: 10.1016/s0014-2999(99)00191-0, PubMed: 10395013.

Hashimoto, R., Hough, C., Nakazawa, T., Yamamoto, T. & Chuang, D.M. (2002) Lithium protection against glutamate excitotoxicity in rat cerebral cortical neurons: Involvement of NMDA receptor inhibition possibly by decreasing NR2B tyrosine phosphorylation. Journal of Neurochemistry, 80, 589–597. DOI: 10.1046/j.0022-3042.2001.00728.x, PubMed: 11841566.

He, X., Li, Y., Deng, B., Lin, A., Zhang, G., Ma, M., Wang, Y., Yang, Y. & Kang, X. (2022) The PI3K/AKT signalling pathway in inflammation, cell death and glial scar formation after traumatic spinal cord injury: Mechanisms and therapeutic opportunities. Cell Proliferation, 55, e13275. DOI: 10.1111/cpr.13275, PubMed: 35754255.

Hedya, S.A., Avula, A. & Swoboda, H.D. (updated 2023) Lithium toxicity. StatPearls [Internet]. In: StatPearls Publishing: Treasure Island, (FL), USA, p. 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499992/.

Hesselink, J.M.K. & Stahl, S.M. (2018) Phenytoin in bipolar depression: An old chapter, but not yet properly evaluated. Journal of Mood Disorders and Therapy, 1, 24–28. https://scholars.direct/Articles/mood-disorders/jmdth-1-003.php?jid=mood-disorders. DOI: 10.36959/418/579.

Hoxhaj, G. & Manning, B.D. (2020) The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism. Nature Reviews. Cancer, 20, 74–88. DOI: 10.1038/s41568-019-0216-7, PubMed: 31686003.

Hughes, C.R. & Keele, N.B. (2006) Phenytoin normalizes exaggerated fear behavior in p-chlorophenylalanine (PCPA)-treated rats. Epilepsy and Behavior: E&B, 9, 557–563. DOI: 10.1016/j.yebeh.2006.09.002, PubMed: 17045847.

Hui, Z., Guang-Yu, M., Chong-Tao, X., Quan, Y. & Xiao-Hu, X. (2005) Phenytoin reverses the chronic stress-induced impairment of memory consolidation for water maze training and depression of LTP in rat hippocampal CA1 region, but does not affect motor activity. Brain Research. Cognitive Brain Research, 24, 380–385. DOI: 10.1016/j.cogbrainres.2005.02.014, PubMed: 16099351.

Inan, S.Y., Yalcin, I. & Aksu, F. (2004) Dual effects of nitric oxide in the mouse forced swimming test: Possible contribution of nitric oxide-mediated serotonin release and potassium channel modulation. Pharmacology, Biochemistry, and Behavior, 77, 457–464. DOI: 10.1016/j.pbb.2003.12.024, PubMed: 15006455.

Inselman, A.L. & Hansen, D.K. (2014) Phenytoin. Encyclopedia of Toxicology, 3rd edn (edited by P. Wexler). Publisher: Publisher: ScienceDirect, Vol. 2014, pp. 895–897. DOI: 10.1016/B978-0-12-386454-3.00771-5.

Iorga, A. & Horowitz, B.Z. (updated 2023) Phenytoin toxicity. StatPearls [Internet]. In: StatPearls Publishing: Treasure Island, (FL), USA, p. 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482444/.

Jakobsson, E., Argüello-Miranda, O., Chiu, S.W., Fazal, Z., Kruczek, J., Nunez-Corrales, S., Pandit, S. & Pritchet, L. (2017) Towards a unified understanding of lithium action in basic biology and its significance for applied biology. Journal of Membrane Biology, 250, 587–604. DOI: 10.1007/s00232-017-9998-2, PubMed: 29127487.

Jaworski, T. (2020) Control of neuronal excitability by GSK-3beta: Epilepsy and beyond. Biochimica et Biophysica Acta. Molecular Cell Research, 1867, 118745. DOI: 10.1016/j.bbamcr.2020.118745, PubMed: 32450268.

Jensen, H.V., Hemmingsen, L., Holm, J., Christensen, E.M. & Aggernaes, H. (1992) Urinary excretion of albumin and retinol-binding protein in lithium-treated patients: A longitudinal study. Acta Psychiatrica Scandinavica, 85, 480–483. DOI: 10.1111/j.1600-0447.1992.tb03215.x, PubMed: 1642133.

Joca, S.R.L., Sartim, A.G., Roncalho, A.L., Diniz, C.F.A. & Wegener, G. (2019) Nitric oxide signalling and antidepressant action revisited. Cell and Tissue Research, 377, 45–58. DOI: 10.1007/s00441-018-02987-4, PubMed: 30649612.

Kaidanovich-Beilin, O., Milman, A., Weizman, A., Pick, C.G. & Eldar-Finkelman, H. (2004) Rapid antidepressive-like activity of specific glycogen synthase kinase-3 inhibitor and its effect on beta-catenin in mouse hippocampus. Biological Psychiatry, 55, 781–784. DOI: 10.1016/j.biopsych.2004.01.008, PubMed: 15050857.

Kalantari, H., Salimi, A., Rezaie, A., Jazayeri Shushtari, F. & Goudarzi, M. (2015) Evaluation of sub-acute oral toxicity of lithium carbonate microemulsion (nano size) on liver and kidney of mice. Jundishapur Journal of Natural Pharmaceutical Products, 10, e22312. DOI: 10.17795/jjnpp-22312, PubMed: 25866723.

Kammerer, M., Brawek, B., Freiman, T.M., Jackisch, R. & Feuerstein, T.J. (2011) Effects of antiepileptic drugs on glutamate release from rat and human neocortical synaptosomes. Naunyn-Schmiedeberg’s Archives of Pharmacology, 383, 531–542. DOI: 10.1007/s00210-011-0620-3, PubMed: 21448570.

Karege, F., Perroud, N., Burkhardt, S., Schwald, M., Ballmann, E., La Harpe, R. & Malafosse, A. (2007) Alteration in kinase activity but not in protein levels of protein kinase B and glycogen synthase kinase-3beta in ventral prefrontal cortex of depressed suicide victims. Biological Psychiatry, 61, 240–245. DOI: 10.1016/j.biopsych.2006.04.036, PubMed: 16876135.

Keppel Hesselink, J.M. (2017) Phenytoin: A step by step insight into its multiple mechanisms of action-80 years of mechanistic studies in neuropharmacology. Journal of Neurology, 264, 2043–2047. DOI: 10.1007/s00415-017-8465-4, PubMed: 28349209.

Kim, J.S., Chang, M.Y., Yu, I.T., Kim, J.H., Lee, S.H., Lee, Y.S. & Son, H. (2004) Lithium selectively increases neuronal differentiation of hippocampal neural progenitor cells both in vitro and in vivo. Journal of Neurochemistry, 89, 324–336. DOI: 10.1046/j.1471-4159.2004.02329.x, PubMed: 15056276.

Kishore, B.K. & Ecelbarger, C.M. (2013) Lithium: A versatile tool for understanding renal physiology. American Journal of Physiology. Renal Physiology, 304, F1139–F1149. DOI: 10.1152/ajprenal.00718.2012, PubMed: 23408166.

Kitagishi, Y., Kobayashi, M., Kikuta, K. & Matsuda, S. (2012) Roles of PI3K/AKT/GSK3/mTOR pathway in cell signaling of mental illnesses. Depression Research and Treatment, 2012, 752563. DOI: 10.1155/2012/752563, PubMed: 23320155.

Kopsky, D.J. & Keppel Hesselink, J.M. (2017) Phenytoin in topical formulations augments pain reduction of other topically applied analgesics in the treatment of trigeminal neuralgia. Journal of Clinical Anesthesia, 38, 154–155. DOI: 10.1016/j.jclinane.2017.01.040, PubMed: 28372657.

Krishnan, V., Han, M.H., Mazei-Robison, M., Iñiguez, S.D., Ables, J.L., Vialou, V., Berton, O., Ghose, S., Covington, H.E., III, Wiley, M.D., Henderson, R.P., Neve, R.L., Eisch, A.J., Tamminga, C.A., Russo, S.J., Bolaños, C.A. & Nestler, E.J. (2008) AKT signaling within the ventral tegmental area regulates cellular and behavioral responses to stressful stimuli. Biological Psychiatry, 64, 691–700. DOI: 10.1016/j.biopsych.2008.06.003, PubMed: 18639865.

Kuo, C.C. & Hess, P. (1993) Characterization of the high-affinity Ca2+ binding sites in the L-type Ca2+ channel pore in rat phaeochromocytoma cells. Journal of Physiology, 466, 657–682. DOI: 10.1113/jphysiol.1993.sp019739, PubMed: 8410711.

Lauterborn, J.C., Lynch, G., Vanderklish, P., Arai, A. & Gall, C.M. (2000) Positive modulation of AMPA receptors increases neurotrophin expression by hippocampal and cortical neurons. Journal of Neuroscience, 20, 8–21. DOI: 10.1523/JNEUROSCI.20-01-00008.2000, PubMed: 10627576.

Leeder, J.S. (1998) Mechanisms of idiosyncratic hypersensitivity reactions to antiepileptic drugs. Epilepsia, 39 (Supplement 7), S8–S16. DOI: 10.1111/j.1528-1157.1998.tb01679.x, PubMed: 9798756.

Legutko, B., Li, X. & Skolnick, P. (2001) Regulation of BDNF expression in primary neuron culture by LY392098, a novel AMPA receptor potentiator. Neuropharmacology, 40, 1019–1027. DOI: 10.1016/s0028-3908(01)00006-5, PubMed: 11406193.

Li, X., Zhu, W., Roh, M.S., Friedman, A.B., Rosborough, K. & Jope, R.S. (2004) In vivo regulation of glycogen synthase kinase-3beta (GSK3beta) by serotonergic activity in mouse brain. Neuropsychopharmacology, 29, 1426–1431. DOI: 10.1038/sj.npp.1300439, PubMed: 15039769.

Lu, F.F., Su, P., Liu, F. & Daskalakis, Z.J. (2012) Activation of GABA(B) receptors inhibits protein kinase B/glycogen synthase kinase 3 signaling. Molecular Brain, 5, 41. DOI: 10.1186/1756-6606-5-41, PubMed: 23192081.

Lundberg, M., Millischer, V., Backlund, L., Martinsson, L., Stenvinkel, P., Sellgren, C.M., Lavebratt, C. & Schalling, M. (2020) Lithium and the interplay between telomeres and mitochondria in bipolar disorder. Frontiers in Psychiatry, 11, 586083. DOI: 10.3389/fpsyt.2020.586083, PubMed: 33132941.

Lynch, J.W. (2009) Native glycine receptor subtypes and their physiological roles. Neuropharmacology, 56, 303–309. DOI: 10.1016/j.neuropharm.2008.07.034, PubMed: 18721822.

Mackowiak, M., O’Neill, M.J., Hicks, C.A., Bleakman, D. & Skolnick, P. (2002) An AMPA receptor potentiator modulates hippocampal expression of BDNF: An in vivo study. Neuropharmacology, 43, 1–10. DOI: 10.1016/S0028-3908(02)00066-7, PubMed: 12213254.

Malhi, G.S., Masson, M. & Bellivier, F. (2017) The science and practice of lithium therapy. Springer International Publishing. p. 61. DOI: 10.1007/978-3-319-45923-3.

Malhi, G.S., Tanious, M., Das, P., Coulston, C.M. & Berk, M. (2013) Potential mechanisms of action of lithium in bipolar disorder. Current understanding. CNS Drugs, 27, 135–153. DOI: 10.1007/s40263-013-0039-0, PubMed: 23371914.

Manning, B.D. & Toker, A. (2017) AKT/PKB signaling: Navigating the network. Cell, 169, 381–405. DOI: 10.1016/j.cell.2017.04.001, PubMed: 28431241.

Mariotti, V., Melissari, E., Amar, S., Conte, A., Belmaker, R.H., Agam, G. & Pellegrini, S. (2010) Effect of prolonged phenytoin administration on rat brain gene expression assessed by DNA microarrays. Experimental Biology and Medicine, 235, 300–310. DOI: 10.1258/ebm.2009.009225, PubMed: 20404047.

Markowitz, G.S., Radhakrishnan, J., Kambham, N., Valeri, A.M., Hines, W.H. & D’Agati, V.D. (2000) Lithium nephrotoxicity: A progressive combined glomerular and tubulointerstitial nephropathy. Journal of the American Society of Nephrology, 11, 1439–1448. DOI: 10.1681/ASN.V1181439, PubMed: 10906157.

Marmol, F., Ferrero, Y. & Sanchez, J. (2019) Effects of lithium treatment on oxidative stress markers in mitochondrial complex I and complex III inhibition and after CO2 exposure in SH-SY5Y cells. Neurology and Neurobiology, 2, 1–8. DOI: 10.31487/j.NNB.2019.01.001.

Maruta, S., Suzuki, E., Yokoyama, M., Sato, T., Inada, K., Watanabe, S. & Miyaoka, H. (2005) Effects of intraperitoneally injected lithium, imipramine and diazepam on nitrate levels in rat amygdala. Psychiatry and Clinical Neurosciences, 59, 358–361. DOI: 10.1111/j.1440-1819.2005.01383.x, PubMed: 15896232.

Massot, O., Rousselle, J.C., Fillion, M.P., Januel, D., Plantefol, M. & Fillion, G. (1999) 5-HT1B receptors: A novel target for lithium. Possible involvement in mood disorders. Neuropsychopharmacology, 21, 530–541. DOI: 10.1016/S0893-133X(99)00042-1, PubMed: 10481837.

Maurer, I.C., Schippel, P. & Volz, H.P. (2009) Lithium-induced enhancement of mitochondrial oxidative phosphorylation in human brain tissue. Bipolar Disorders, 11, 515–522. DOI: 10.1111/j.1399-5618.2009.00729.x, PubMed: 19624390.

McKnight, R.F., de La Motte de Broöns de Vauvert, S.J.G.N., Chesney, E., Amit, B.H., Geddes, J. & Cipriani, A. (2019) Lithium for acute mania. Cochrane Database of Systematic Reviews, 6, Art. no.: CD004048. DOI: 10.1002/14651858.CD004048.pub4. Accessed 25 July 2023. PubMed: 31152444.

Meshkibaf, M.H., Subhash, M.N., Lakshmana, K.M., Rao, B.S. & Sridhara, B.S. (1995) Effect of chronic administration of phenytoin on regional monoamine levels in rat brain. Neurochemical Research, 20, 773–778. DOI: 10.1007/BF00969688, PubMed: 7477669.

Montgomery, M.C., Chou, J.W., McPharlin, T.O., Baird, G.S. & Anderson, G.D. (2019) Predicting unbound phenytoin concentrations: Effects of albumin concentration and kidney dysfunction. Pharmacotherapy, 39, 756–766. DOI: 10.1002/phar.2273, PubMed: 31067355.

Musazzi, L., Treccani, G., Mallei, A. & Popoli, M. (2013) The action of antidepressants on the glutamate system: Regulation of glutamate release and glutamate receptors. Biological Psychiatry, 73, 1180–1188. DOI: 10.1016/j.biopsych.2012.11.009, PubMed: 23273725.

Nahman, S., Belmaker, R.H. & Azab, A.N. (2012) Effects of lithium on lipopolysaccharide-induced inflammation in rat primary glia cells. Innate Immunity, 18, 447–458. DOI: 10.1177/1753425911421512, PubMed: 21994254.

Nakajima, M., Yamanaka, H., Fujiwara, R., Katoh, M. & Yokoi, T. (2007) Stereoselective glucuronidation of 5-(4′-hydroxyphenyl)-5-phenylhydantoin by human UDP-glucuronosyltransferase (UGT) 1A1, UGT1A9, and UGT2B15: Effects of UGT-UGT interactions. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 35, 1679–1686. DOI: 10.1124/dmd.107.015909, PubMed: 17576806.

Nassar, A. & Azab, A.N. (2014) Effects of lithium on inflammation. ACS Chemical Neuroscience, 5, 451–458. DOI: 10.1021/cn500038f, PubMed: 24803181.

Nciri, R., Desmoulin, F., Allagui, M.S., Murat, J.C., Feki, A.E., Vincent, C. & Croute, F. (2013) Neuroprotective effects of chronic exposure of SH-SY5Y to low lithium concentration involve glycolysis stimulation, extracellular pyruvate accumulation and resistance to oxidative stress. International Journal of Neuropsychopharmacology, 16, 365–376. DOI: 10.1017/S1461145712000132, PubMed: 22436355.

O’Brien, W.T., Harper, A.D., Jové, F., Woodgett, J.R., Maretto, S., Piccolo, S. & Klein, P.S. (2004) Glycogen synthase kinase-3beta haploinsufficiency mimics the behavioral and molecular effects of lithium. Journal of Neuroscience, 24, 6791–6798. DOI: 10.1523/JNEUROSCI.4753-03.2004, PubMed: 15282284.

Ohmori, H., Yamashita, K., Hatta, T., Yamasaki, S., Kawamura, M., Higashi, Y., Yata, N. & Yasuda, M. (1997) Effects of low-dose phenytoin administered to newborn mice on developing cerebellum. Neurotoxicology and Teratology, 19, 205–211. DOI: 10.1016/s0892-0362(97)00014-7, PubMed: 9200141.

Omata, N., Chiu, C.T., Moya, P.R., Leng, Y., Wang, Z., Hunsberger, J.G., Leeds, P. & Chuang, D.M. (2011) Lentivirally mediated GSK-3β silencing in the hippocampal dentate gyrus induces antidepressant-like effects in stressed mice. International Journal of Neuropsychopharmacology, 14, 711–717. DOI: 10.1017/S1461145710000726, PubMed: 20604988.

Ostadhadi, S., Norouzi-Javidan, A., Nikoui, V., Zolfaghari, S., Moradi, A. & Dehpour, A.R. (2018) Nitric oxide involvement in additive antidepressant-like effect of agmatine and lithium in mice forced swim test. Psychiatry Research, 266, 262–268. DOI: 10.1016/j.psychres.2018.03.010, PubMed: 29573854.

Ozdemir, O. (2016) Voltage-gated sodium channels dysfunction in depression: The hypothesis. Journal of Mood Disorders, 6, 36–40. DOI: 10.5455/jmood.20151207010014.

Palumbo, S., Paterson, C., Yang, F., Hood, V.L. & Law, A.J. (2021) PKBβ/AKT2 deficiency impacts brain mTOR signaling, prefrontal cortical physiology, hippocampal plasticity and select murine behaviors. Molecular Psychiatry, 26, 411–428. DOI: 10.1038/s41380-020-00964-4, PubMed: 33328589.

Patocka, J., Wu, Q., Nepovimova, E. & Kuca, K. (2020) Phenytoin – An anti-seizure drug: Overview of its chemistry, pharmacology and toxicology. Food and Chemical Toxicology, 142, 111393. DOI: 10.1016/j.fct.2020.111393, PubMed: 32376339.

Petit-Demouliere, B., Chenu, F. & Bourin, M. (2005) Forced swimming test in mice: A review of antidepressant activity. Psychopharmacology, 177, 245–255. DOI: 10.1007/s00213-004-2048-7, PubMed: 15609067.

Petty, F. (1994) Plasma concentrations of gamma-aminobutyric acid (GABA) and mood disorders: A blood test for manic depressive disease? Clinical Chemistry, 40, 296–302. https://pubmed.ncbi.nlm.nih.gov/8313610/. DOI: 10.1093/clinchem/40.2.296, PubMed: 8313610.

Petty, F., Kramer, G.L., Dunnam, D. & Rush, A.J. (1990) Plasma GABA in mood disorders. Psychopharmacology Bulletin, 26, 157–161. https://pubmed.ncbi.nlm.nih.gov/2236451/. PubMed: 2236451.

Pietruczuk, K., Jóźwik, A., Ruckemann-Dziurdzińska, K., Bryl, E. & Witkowski, J.M. (2009) Cytoprotective effect of lithium against spontaneous and induced apoptosis of lymphoid cell line MOLT-4. Folia Histochemica et Cytobiologica, 47, 639–646. DOI: 10.2478/v10042-009-0118-8, PubMed: 20430733.

Pittaluga, A., Bonfanti, A. & Raiteri, M. (1997) Differential desensitization of ionotropic non-NMDA receptors having distinct neuronal location and function. Naunyn-Schmiedeberg’s Archives of Pharmacology, 356, 29–38. DOI: 10.1007/pl00005025, PubMed: 9228187.

Pittaluga, A., Raiteri, L., Longordo, F., Luccini, E., Barbiero, V.S., Racagni, G., Popoli, M. & Raiteri, M. (2007) Antidepressant treatments and function of glutamate ionotropic receptors mediating amine release in hippocampus. Neuropharmacology, 53, 27–36. DOI: 10.1016/j.neuropharm.2007.04.006, PubMed: 17543354.

Pláteník, J., Fišar, Z., Buchal, R., Jirák, R., Kitzlerová, E., Zvěřová, M. & Raboch, J. (2014) GSK3β, CREB, and BDNF in peripheral blood of patients with Alzheimer’s disease and depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 50, 83–93. DOI: 10.1016/j.pnpbp.2013.12.001, PubMed: 24334212.

Porsolt, R.D., Bertin, A. & Jalfre, M. (1977) Behavioral despair in mice: A primary screening test for antidepressants. Archives Internationales de Pharmacodynamie et de Therapie, 229, 327–336. PubMed: 596982.

Prakash, S., Rathore, C., Rana, K. & Patel, H. (2021) Antiepileptic drugs and serotonin syndrome- A systematic review of case series and case reports. Seizure, 91, 117–131. DOI: 10.1016/j.seizure.2021.06.004, PubMed: 34153897.

Prakriya, M. & Mennerick, S. (2000) Selective depression of low-release probability excitatory synapses by sodium channel blockers. Neuron, 26, 671–682. DOI: 10.1016/s0896-6273(00)81203-9, PubMed: 10896162.

Rahajeng, B., Ikawati, Z., Andayani, T.M. & Dwiprahasto, I. (2018) A retrospective study: The off-label use of anticonvulsants at a private hospital in Indonesia. International Journal of Pharmacy and Pharmaceutical Sciences, 10, 119–122. https://journals.innovareacademics.in/index.php/ijpps/article/view/25388/14654. DOI: 10.22159/ijpps.2018v10i5.25388.

Rangel-Barajas, C., Coronel, I. & Florán, B. (2015) Dopamine receptors and neurodegeneration. Aging and Disease, 6, 349–368. DOI: 10.14336/AD.2015.0330, PubMed: 26425390.

Rege, S. (2023) Lithium’s mechanism of action – A synopsis and visual guide. Posted on February 9, 2019, last update. Lithium’s Mechanism of Action – A Synopsis and Visual Guide. psychscenehub.com. 24 November, 2023. (psychscenehub.com). https://psychscenehub.com/psychinsights/lithium-mechanism-action-synopsis-visual-guide/.

Richelson, E. (1977) Lithium ion entry through the sodium channel of cultured mouse neuroblastoma cells: A biochemical study. Science, 196, 1001–1002. DOI: 10.1126/science.860126, PubMed: 860126.

Richerson, G.B. & Buchanan, G.F. (2011) The serotonin axis: Shared mechanisms in seizures, depression, and SUDEP. Epilepsia, 52 (Supplement 1) (Supplement 1)(Suppl 1):28-38, 28–38. DOI: 10.1111/j.1528-1167.2010.02908.x, PubMed: 21214537.

Rogawski, M.A. & Löscher, W. (2004) The neurobiology of antiepileptic drugs. Nature Reviews. Neuroscience, 5, 553–564. DOI: 10.1038/nrn1430, PubMed: 15208697.

Rosenblat, J.D., Brietzke, E., Mansur, R.B., Maruschak, N.A., Lee, Y. & McIntyre, R.S. (2015) Inflammation as a neurobiological substrate of cognitive impairment in bipolar disorder: Evidence, pathophysiology and treatment implications. Journal of Affective Disorders, 188, 149–159. DOI: 10.1016/j.jad.2015.08.058, PubMed: 26363613.

Rosenblat, J.D. & McIntyre, R.S. (2016) Bipolar disorder and inflammation. Psychiatric Clinics of North America, 39, 125–137. DOI: 10.1016/j.psc.2015.09.006, PubMed: 26876323.

Sadeghipour, H., Ghasemi, M., Nobakht, M., Ebrahimi, F. & Dehpour, A.R. (2007) Effect of chronic lithium administration on endothelium-dependent relaxation of rat corpus cavernosum: The role of nitric oxide and cyclooxygenase pathways. BJU International, 99, 177–182. DOI: 10.1111/j.1464-410X.2006.06530.x, PubMed: 17034495.

Scaccia, A. Everything you need to know about serotonin. Medically reviewed by Debra Rose Wilson. Updated on 17 April, 2023 https://www.healthline.com/health/mental-health/serotonin.

Scheuch, K., Höltje, M., Budde, H., Lautenschlager, M., Heinz, A., Ahnert-Hilger, G. & Priller, J. (2010) Lithium modulates tryptophan hydroxylase 2 gene expression and serotonin release in primary cultures of serotonergic raphe neurons. Brain Research, 1307, 14–21. DOI: 10.1016/j.brainres.2009.10.027, PubMed: 19840776.

Schrauzer, G.N. (2002) Lithium: Occurrence, dietary intakes, nutritional essentiality. Journal of the American College of Nutrition, 21, 14–21. DOI: 10.1080/07315724.2002.10719188, PubMed: 11838882.

Shao, L., Young, L.T. & Wang, J.F. (2005) Chronic treatment with mood stabilizers lithium and valproate prevents excitotoxicity by inhibiting oxidative stress in rat cerebral cortical cells. Biological Psychiatry, 58, 879–884. DOI: 10.1016/j.biopsych.2005.04.052, PubMed: 16005436.

Shorter, E. (2009) The history of lithium therapy. Bipolar Disorders, 11 (Supplement 2), 4–9. DOI: 10.1111/j.1399-5618.2009.00706.x, PubMed: 19538681.

Shukla, G.S. (1987) Mechanism of lithium action: In vivo and in vitro effects of alkali metals on brain superoxide dismutase. Pharmacology, Biochemistry, and Behavior, 26, 235–240. DOI: 10.1016/0091-3057(87)90111-0, PubMed: 3033694.

Snitow, M.E., Bhansali, R.S. & Klein, P.S. (2021) Lithium and therapeutic targeting of GSK-3. Cells, 10, 255. DOI: 10.3390/cells10020255, PubMed: 33525562.

Solntseva, E.I., Bukanova, J.V., Kondratenko, R.V. & Skrebitsky, V.G. (2016) Lithium ions in nanomolar concentration modulate glycine-activated chloride current in rat hippocampal neurons. Neurochemistry International, 94, 67–73. DOI: 10.1016/j.neuint.2016.02.007, PubMed: 26893189.

Song, W., Chattipakorn, S.C. & McMahon, L.L. (2006) Glycine-gated chloride channels depress synaptic transmission in rat hippocampus. Journal of Neurophysiology, 95, 2366–2379. DOI: 10.1152/jn.00386.2005, PubMed: 16381810.

Stambolic, V., Ruel, L. & Woodgett, J.R. (1996) Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Current Biology, 6, 1664–1668. DOI: 10.1016/s0960-9822(02)70790-2. Erratum in: Current Biology (1997), 7, 196.

Suzuki, A.M., Yoshimura, A., Ozaki, Y., Kaneko, T. & Hara, Y. (2009) Cyclosporin A and phenytoin modulate inflammatory responses. Journal of Dental Research, 88, 1131–1136. DOI: 10.1177/0022034509350566, PubMed: 19897783.

Szeto, H.H. (2006) Mitochondria-targeted peptide antioxidants: Novel neuroprotective agents. AAPS Journal, 8, E521–E531. DOI: 10.1208/aapsj080362, PubMed: 17025271.

Tandon, P., Wong, N. & Zaltzman, J.S. (2015) Lithium-induced minimal change disease and acute kidney injury. North American Journal of Medical Sciences, 7, 328–331. DOI: 10.4103/1947-2714.161252, PubMed: 26258081.

Thompson, A.N., Kim, I., Panosian, T.D., Iverson, T.M., Allen, T.W. & Nimigean, C.M. (2009) Mechanism of potassium-channel selectivity revealed by Na(+) and Li(+) binding sites within the KcsA pore. Nature Structural and Molecular Biology, 16, 1317–1324. DOI: 10.1038/nsmb.1703, PubMed: 19946269.

Thomsen, K. & Shirley, D.G. (2006) A hypothesis linking sodium and lithium reabsorption in the distal nephron. Nephrology, Dialysis, Transplantation, 21, 869–880. DOI: 10.1093/ndt/gfk029, PubMed: 16410274.

Tondo, L., Alda, M., Bauer, M., Bergink, V., Grof, P., Hajek, T., Lewitka, U., Licht, R.W., Manchia, M., Müller-Oerlinghausen, B., Nielsen, R.E., Selo, M., Simhandl, C., Baldessarini, R.J. & International Group for Studies of Lithium (IGSLi) (2019) Clinical use of lithium salts: Guide for users and prescribers. International Journal of Bipolar Disorders, 7, 16. DOI: 10.1186/s40345-019-0151-2, PubMed: 31328245.

Treiser, S.L., Cascio, C.S., O’Donohue, T.L., Thoa, N.B., Jacobowitz, D.M. & Kellar, K.J. (1981) Lithium increases serotonin release and decreases serotonin receptors in the hippocampus. Science, 213, 1529–1531. DOI: 10.1126/science.6269180, PubMed: 6269180.

Wada, A., Yokoo, H., Yanagita, T. & Kobayashi, H. (2005) Lithium: Potential therapeutics against acute brain injuries and chronic neurodegenerative diseases. Journal of Pharmacological Sciences, 99, 307–321. DOI: 10.1254/jphs.crj05009x, PubMed: 16340157.

Wang, H.M., Zhang, T., Li, Q., Huang, J.K., Chen, R.F. & Sun, X.J. (2013) Inhibition of glycogen synthase kinase-3β by lithium chloride suppresses 6-hydroxydopamine-induced inflammatory response in primary cultured astrocytes. Neurochemistry International, 63, 345–353. DOI: 10.1016/j.neuint.2013.07.003, PubMed: 23871716.

Wang, J.F. (2007) Defects of mitochondrial electron transport chain in bipolar disorder: Implications for mood-stabilizing treatment. Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie, 52, 753–762. DOI: 10.1177/070674370705201202, PubMed: 18186175.

Wang, J.F., Shao, L., Sun, X. & Young, L.T. (2004) Glutathione S-transferase is a novel target for mood stabilizing drugs in primary cultured neurons. Journal of Neurochemistry, 88, 1477–1484. DOI: 10.1046/j.1471-4159.2003.02276.x, PubMed: 15009649.

Wang, J.K., Andrews, H. & Thukral, V. (1992) Presynaptic glutamate receptors regulate noradrenaline release from isolated nerve terminals. Journal of Neurochemistry, 58, 204–211. DOI: 10.1111/j.1471-4159.1992.tb09297.x, PubMed: 1345765.

Wegener, G., Volke, V., Bandpey, Z. & Rosenberg, R. (2001) Nitric oxide modulates lithium-induced conditioned taste aversion. Behavioural Brain Research, 118, 195–200. DOI: 10.1016/S0166-4328(00)00329-6, PubMed: 11164517.

Won, E. & Kim, Y.K. (2017) An oldie but goodie: Lithium in the treatment of bipolar disorder through neuroprotective and neurotrophic mechanisms. International Journal of Molecular Sciences, 18, 2679. DOI: 10.3390/ijms18122679, PubMed: 29232923.

Wróbel, A., Serefko, A., Wlaź, P. & Poleszak, E. (2015) The effect of imipramine, ketamine, and zinc in the mouse model of depression. Metabolic Brain Disease, 30, 1379–1386. DOI: 10.1007/s11011-015-9709-6, PubMed: 26155916.

Wu, M.F. & Lim, W.H. (2013) Phenytoin: A guide to therapeutic drug monitoring. Proceedings of Singapore Healthcare, 22, 198–202. DOI: 10.1177/201010581302200307.

Xu, T.L. & Gong, N. (2010) Glycine and glycine receptor signaling in hippocampal neurons: Diversity, function and regulation. Progress in Neurobiology, 91, 349–361. DOI: 10.1016/j.pneurobio.2010.04.008, PubMed: 20438799.

Yanagita, T., Maruta, T., Uezono, Y., Satoh, S., Yoshikawa, N., Nemoto, T., Kobayashi, H. & Wada, A. (2007) Lithium inhibits function of voltage-dependent sodium channels and catecholamine secretion independent of glycogen synthase kinase-3 in adrenal chromaffin cells. Neuropharmacology, 53, 881–889. DOI: 10.1016/j.neuropharm.2007.08.018, PubMed: 17950380.

Yeung, M., Treit, D. & Dickson, C.T. (2012) A critical test of the hippocampal theta model of anxiolytic drug action. Neuropharmacology, 62, 155–160. DOI: 10.1016/j.neuropharm.2011.06.011, PubMed: 21723303.

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