@2024 Afarand., IRAN
ISSN: 2252-0805 The Horizon of Medical Sciences 2018;24(2):79-87
ISSN: 2252-0805 The Horizon of Medical Sciences 2018;24(2):79-87
Anxiolytic Effect of Lithium Chloride in Model of PTZ-Induced Seizure
ARTICLE INFO
Article Type
Original ResearchAuthors
Edalatmanesh MA (*)Yazdani M (1)
Davoodi A (2)
Rafiei S (3)
(*) Department of Biology, College of Sciences, Shiraz Branch, Islamic Azad University, Shiraz, Iran
(1) Department of Biology, College of Sciences, Shiraz Branch, Islamic Azad University, Shiraz, Iran
(2) Department of Psychology, College of Humanities,, Islamic Azad University, Shiraz Branch , Shiraz, Iran
(3) Department of Exercise Physiology, Kish International Campus, Tehran University, Kish, Iran
Correspondence
Article History
Received: October 28, 2017Accepted: May 2, 2018
ePublished: May 16, 2018
ABSTRACT
Aims
Epilepsy is a brain disorder characterized by repeated and spontaneous
attacks which can lead to neuronal decline or death and behavioral disorders,
such as anxiety, and numerous studies have shown neuroprotective effects of the
lithium. This study evaluated the anxiolytic effect of administration of lithium
chloride (LiCl) in penthylentetrazole (PTZ) induced seizure rat model.
Materials & Methods In present experimental study, 50 male Wistar rats were divided into 5 groups control, PTZ+Saline, PTZ+Li20, PTZ+Li40 and PTZ+Li80, randomly. To induce convulsions and epilepsy model, repeated doses of PTZ were injected (40 mg/kg, i.p) for 5 consecutive days. After observing the 5 stages of seizures based on Racine’s scale, test groups, received lithium chloride in three doses (20, 40 and 80 mg/kg/BW, i.p) for 14 days. In order to assess anxiety and exploratory behaviors, elevated plus maze and open field tests were done. Then, the hippocampal level of BDNF was measured using ELISA. The results were analyzed by ANOVA and Tukey post hoc.
Findings Our finding showed an increased rate of anxiety with low level of hippocampal BDNF in PTZ receiver rats. Treatment with lithium chloride especially at the lowest dose (20 mg/kg) showed a significant difference in reducing anxiety and increasing of BDNF level compared to the PTZ receiver group.
Conclusion Anxiolytic-like effects of lithium may improve the symptoms of anxiety in PTZ-induced seizure.
Materials & Methods In present experimental study, 50 male Wistar rats were divided into 5 groups control, PTZ+Saline, PTZ+Li20, PTZ+Li40 and PTZ+Li80, randomly. To induce convulsions and epilepsy model, repeated doses of PTZ were injected (40 mg/kg, i.p) for 5 consecutive days. After observing the 5 stages of seizures based on Racine’s scale, test groups, received lithium chloride in three doses (20, 40 and 80 mg/kg/BW, i.p) for 14 days. In order to assess anxiety and exploratory behaviors, elevated plus maze and open field tests were done. Then, the hippocampal level of BDNF was measured using ELISA. The results were analyzed by ANOVA and Tukey post hoc.
Findings Our finding showed an increased rate of anxiety with low level of hippocampal BDNF in PTZ receiver rats. Treatment with lithium chloride especially at the lowest dose (20 mg/kg) showed a significant difference in reducing anxiety and increasing of BDNF level compared to the PTZ receiver group.
Conclusion Anxiolytic-like effects of lithium may improve the symptoms of anxiety in PTZ-induced seizure.
CITATION LINKS
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[3]Zamponi GW, Lory P, Perez-Reyes E. Role of voltage-gated calcium channels in epilepsy. Pflugers Arch. 2010;460(2):395-403
[4]Hui Yin Y, Ahmad N, Makmor-Bakry M. Pathogenesis of epilepsy: Challenges in animal models. Iran J Basic Med Sci. 2013;16(11):1119-32
[5]- Mula M, Pini S, Cassano GB. The role of anticonvulsant drugs in anxiety disorders: A critical review of the evidence. J Clin Psychopharmacol .2007;27(3):263-72
[6]Neumeister A, Bain E, Nugent AC, Carson RE, Bonne O, Luckenbaugh DA, et al. Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci. 2004;24(3):589-91
[7]Jung ME, Lal H, Gatch MB. The discriminative stimulus effects of pentylenetetrazol as a model of anxiety: Recent developments. Neurosci Biobehav Rev. 2002;26(4):429-39.
[8]Lei P, Ayton S, Bush AI, Adlard PA. GSK-3 in neurodegenerative diseases. Int J Alzheimers Dis. 2011;2011:189246
[9]Tso CY, Chiu KH, Cheung KW. Ceramic insert dislodgment after revision ceramic-on-ceramic total hip arthroplasty. J Arthroplasty. 2010;25(4):660.e5-7.
[10]Quiroz JA, Machado-Vieira R, Zarate CA Jr, Manji HK. Novel insights into lithium's mechanism of action: Neurotrophic and neuroprotective effects. Neuropsychobiology. 2010;62(1):50-60.
[11]Chiu CT, Chuang DM. Neuroprotective action of lithium in disorders of the central nervous system. Zhong Nan Da Xue Bao Yi Xue Ban. 2011;36(6):461-76.
[12]Su H, Zhang W, Guo J, Guo A, Yuan Q, Wu W. Lithium enhances the neuronal differentiation of neural progenitor cells in vitro and after transplantation into the avulsed ventral horn of adult rats through the secretion of brain-derived neurotrophic factor. J Neurochem. 2009;108(6):1385-98.
[13]Wada A. Lithium and neuropsychiatric therapeutics: Neuroplasticity via glycogen synthase kinase-3β, β-catenin, and neurotrophin cascades. J Pharmacol Sci. 2009;110(1):14-28.
[14]Lapmanee S, Charoenphandhu J, Teerapornpuntakit J, Krishnamra N, Charoenphandhu N. Agomelatine, venlafaxine, and running exercise effectively prevent anxiety- and depression-like behaviors and memory impairment in restraint stressed rats. PLoS One. 2017;12(11):e0187671.
[15]Mendez-David I, Guilloux JP, Papp M, Tritschler L, Mocaer E, Gardier AM, et al. S 47445 produces antidepressant- and anxiolytic-like effects through neurogenesis dependent and independent mechanisms. Front Pharmacol. 2017;8:462.
[16]An Y, Inoue T, Kitaichi Y, Chen C, Nakagawa S, Wang C, et al. Combined treatment with subchronic lithium and acute intracerebral mirtazapine microinjection into the median raphe nucleus exerted an anxiolytic-like effect synergistically. Eur J Pharmacol. 2016;783:112-6.
[17]Motaghinejad M, Seyedjavadein Z, Motevalian M, Asadi M. The neuroprotective effect of lithium against high dose methylphenidate: Possible role of BDNF. Neurotoxicology. 2016;56:40-54.
[18]Nikoui V, Javadi-Paydar M, Salehi M, Behestani S, Dehpour AR. Protective effects of lithium on sumatriptan-induced memory impairment in mice. Acta Med Iran. 2016;54(4):226-32.
[19]Smagin DA, Kudryavtseva NN. Anxiogenic and anxiolytic effects of lithium chloride under preventive and therapeutic treatments of male mice with repeated experience of aggression. Zh Vyssh Nerv Deiat Im I P Pavlova. 2014;64(6):646-59. [Russian]
[20]Youngs RM, Chu MS, Meloni EG, Naydenov A, Carlezon WA Jr, Konradi C. Lithium administration to preadolescent rats causes long-lasting increases in anxiety-like behavior and has molecular consequences. J Neurosci. 2006;26(22):6031-9
[21]Roohbakhsh A, Esmaeili H, Asami Z, Arab Baniasad F, Shamsizadeh A, Rezvani ME. Effect of Anethum graveolens hydroalcoholic extract on pentylenetetrazole-induced paroxysm. Horizon Med Sci. 2013;19(1):41-5. [Persian]
[22]Seghatoleslam M, Alipour F, Shafieian R, Hassanzadeh Z, Edalatmanesh MA, Sadeghnia HR, et al. The effects of Nigella sativa on neural damage after pentylenetetrazole induced seizures in rats. J Tradit Complement Med. 2016;6(3):262-8.
[23]Vafaee F, Hosseini M, Hassanzadeh Z, Edalatmanesh MA, Sadeghnia HR, Seghatoleslam M, et al. The Effects of Nigella Sativa Hydro-alcoholic Extract on Memory and Brain Tissues Oxidative Damage after Repeated Seizures in Rats. Iran J Pharm Res. 2015;14(2):547-57.
[24]Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc. 2007;2(2):322-8.
[25]Murray CL, Obiang P, Bannerman D, Cunningham C. Endogenous IL-1 in Cognitive Function and Anxiety: A Study in IL-1RI−/− Mice. PLoS One. 2013;8(10):e78385.
[26]Kalynchuk LE. Long-term amygdala kindling in rats as a model for the study of interictal emotionality in temporal lobe epilepsy. Neurosci Biobehav Rev. 2000;24(7):691-704.
[27]Milman A, Rosenberg A, Weizman R, Pick CG. Mild traumatic brain injury induces persistent cognitive deficits and behavioral disturbances in mice. J Neurotrauma. 2005;22(9):1003-10.
[28]Mazarati AM, Pineda E, Shin D, Tio D, Taylor AN, Sankar R. Comorbidity between epilepsy and depression: Role of hippocampal interleukin-1beta. Neurobiol Dis. 2010;37(2):461-7.
[29]Jones NC, Cardamone L, Williams JP, Salzberg MR, Myers D, O’Brien TJ. Experimental traumatic brain injury induces a pervasive hyperanxious phenotype in rats. J Neurotrauma. 2008;25(11):1367-74.
[30]Detour J, Schroeder H, Desor D, Nehlig A. A 5-month period of epilepsy impairs spatial memory, decreases anxiety, but spares object recognition in the lithium-pilocarpine model in adult rats. Epilepsia. 2005;46(4):499-508.
[31]Kemppainen EJ, Nissinen J, Pitkänen A. Fear conditioning is impaired in systemic kainic acid and amygdala-stimulation models of epilepsy. Epilepsia. 2006;47(5):820-9.
[32]Jessberger S, Nakashima K, Clemenson GD Jr, Mejia E, Mathews E, Ure K, et al. Epigenetic modulation of seizure-induced neurogenesis and cognitive decline. J Neurosci. 2007;27(22):5967-75.
[33]Chauvière L, Rafrafi N, Thinus-Blanc C, Bartolomei F, Esclapez M, Bernard C. Early deficits in spatial memory and theta rhythm in experimental temporal lobe epilepsy. J Neurosci. 2009;29(17):5402-10.
[34]Kastenberger I, Lutsch C, Herzog H, Schwarzer Ch. Influence of sex and genetic background on anxiety-related and stress-induced behavior of prodynorphin deficient mice. PLoS One. 2012;7(3):e34251.
[35]Leach G, Adidharma W, Yan L. Depression-like responses induced by daytime light deficiency in the diurnal grass rat (Arvicanthis niloticus). Plos One. 2013;8(2):e57115.
[36]Godlevsky LS, Muratova TN, Kresyun NV, van Luijtelaar G, Coenen AM. Anxiolytic and antidepressive effects of electric stimulation of the paleocerebellar cortex in pentylenetetrazol kindled rats. Acta Neurobiol Exp (Wars). 2014;74(4):456-64.
[37]Zárraga-Galindo N, Vergara-Aragón P, Rosales-Meléndez S, Ibarra-Guerrero P, Domínguez-Marrufo LE, Oviedo-García RE, et al. Effects of bee products on pentylenetetrazole-induced seizures in the rat. Proc West Pharmacol Soc. 2011;54:33-40.
[38]Liu ZH, Chuang DM, Smith CB. Lithium ameliorates phenotypic deficits in a mouse model of fragile X syndrome. Int J Neuropsychopharmacol. 2011;14(5):618-30.
[39]Yan XB, Hou HL, Wu LM, Liu J, Zhou JN. Lithium regulates hippocampal neurogenesis by ERK pathway and facilitates recovery of spatial learning and memory in rats after transient global cerebral ischemia. Neuropharmacology. 2007;53(4):487-95.
[40]Chen X, Sun W, Pan Y, Yang Q, Cao K, Zhang J, et al. Lithium ameliorates open-field and elevated plus maze behaviors, and brain phospho-glycogen synthase kinase 3-beta expression in fragile X syndrome model mice. Neurosciences (Riyadh). 2013;18(4):356-62.
[41]Hoeller AA, de Carvalho CR, Franco PLC, Formolo DA, Imthon AK, Dos Santos HR, et al. Behavioral and neurochemical consequences of pentylenetetrazol-induced kindling in young and middle-aged rats. Pharmaceuticals (Basel). 2017;10(3).
[42]Kordi Jaz E, Moghimi A, Fereidoni M, Asadi S, Shamsizadeh A, Roohbakhsh A. SB-334867, an orexin receptor 1 antagonist, decreased seizure and anxiety in pentylenetetrazol-kindled rats. Fundam Clin Pharmacol. 2017;31(2):201-7.
[43]Hashimoto R, Takei N, Shimazu K, Christ L, Lu B, Chuang DM. Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: An essential step for neuroprotection against glutamate excitotoxicity. Neuropharmacology. 2002;43(7):1173-9.
[44]Zhen JL, Chang YN, Qu ZZ, Fu T, Liu JQ, Wang WP. Luteolin rescues pentylenetetrazole-induced cognitive impairment in epileptic rats by reducing oxidative stress and activating PKA/CREB/BDNF signaling. Epilepsy Behav. 2016;57(Pt A):177-84.
[45]Moghadas M, Edalatmanesh MA, Hosseini M. Effect of Lithium Chloride on Serum Levels of BDNF, TNF-α, and Wet Weight of Brain in an Animal Model of Depression. Shefaye Khatam. 2014;2(4):9-19.
[46]Liu ZH, Chuang DM, Beebe Smith C. Lithium ameliorates phenotypic deficits in a mouse model of fragile X syndrome. Int J Neuropsychopharmacol. 2011;14(5):618-30.
[2]Naseer MI, Shupeng L, Kim MO. Maternal epileptic seizure induced by pentylenetetrazol: apoptotic neurodegeneration and decreased GABAB1 receptor expression in prenatal rat brain. Mol Brain. 2009;2:20:660-701.
[3]Zamponi GW, Lory P, Perez-Reyes E. Role of voltage-gated calcium channels in epilepsy. Pflugers Arch. 2010;460(2):395-403
[4]Hui Yin Y, Ahmad N, Makmor-Bakry M. Pathogenesis of epilepsy: Challenges in animal models. Iran J Basic Med Sci. 2013;16(11):1119-32
[5]- Mula M, Pini S, Cassano GB. The role of anticonvulsant drugs in anxiety disorders: A critical review of the evidence. J Clin Psychopharmacol .2007;27(3):263-72
[6]Neumeister A, Bain E, Nugent AC, Carson RE, Bonne O, Luckenbaugh DA, et al. Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci. 2004;24(3):589-91
[7]Jung ME, Lal H, Gatch MB. The discriminative stimulus effects of pentylenetetrazol as a model of anxiety: Recent developments. Neurosci Biobehav Rev. 2002;26(4):429-39.
[8]Lei P, Ayton S, Bush AI, Adlard PA. GSK-3 in neurodegenerative diseases. Int J Alzheimers Dis. 2011;2011:189246
[9]Tso CY, Chiu KH, Cheung KW. Ceramic insert dislodgment after revision ceramic-on-ceramic total hip arthroplasty. J Arthroplasty. 2010;25(4):660.e5-7.
[10]Quiroz JA, Machado-Vieira R, Zarate CA Jr, Manji HK. Novel insights into lithium's mechanism of action: Neurotrophic and neuroprotective effects. Neuropsychobiology. 2010;62(1):50-60.
[11]Chiu CT, Chuang DM. Neuroprotective action of lithium in disorders of the central nervous system. Zhong Nan Da Xue Bao Yi Xue Ban. 2011;36(6):461-76.
[12]Su H, Zhang W, Guo J, Guo A, Yuan Q, Wu W. Lithium enhances the neuronal differentiation of neural progenitor cells in vitro and after transplantation into the avulsed ventral horn of adult rats through the secretion of brain-derived neurotrophic factor. J Neurochem. 2009;108(6):1385-98.
[13]Wada A. Lithium and neuropsychiatric therapeutics: Neuroplasticity via glycogen synthase kinase-3β, β-catenin, and neurotrophin cascades. J Pharmacol Sci. 2009;110(1):14-28.
[14]Lapmanee S, Charoenphandhu J, Teerapornpuntakit J, Krishnamra N, Charoenphandhu N. Agomelatine, venlafaxine, and running exercise effectively prevent anxiety- and depression-like behaviors and memory impairment in restraint stressed rats. PLoS One. 2017;12(11):e0187671.
[15]Mendez-David I, Guilloux JP, Papp M, Tritschler L, Mocaer E, Gardier AM, et al. S 47445 produces antidepressant- and anxiolytic-like effects through neurogenesis dependent and independent mechanisms. Front Pharmacol. 2017;8:462.
[16]An Y, Inoue T, Kitaichi Y, Chen C, Nakagawa S, Wang C, et al. Combined treatment with subchronic lithium and acute intracerebral mirtazapine microinjection into the median raphe nucleus exerted an anxiolytic-like effect synergistically. Eur J Pharmacol. 2016;783:112-6.
[17]Motaghinejad M, Seyedjavadein Z, Motevalian M, Asadi M. The neuroprotective effect of lithium against high dose methylphenidate: Possible role of BDNF. Neurotoxicology. 2016;56:40-54.
[18]Nikoui V, Javadi-Paydar M, Salehi M, Behestani S, Dehpour AR. Protective effects of lithium on sumatriptan-induced memory impairment in mice. Acta Med Iran. 2016;54(4):226-32.
[19]Smagin DA, Kudryavtseva NN. Anxiogenic and anxiolytic effects of lithium chloride under preventive and therapeutic treatments of male mice with repeated experience of aggression. Zh Vyssh Nerv Deiat Im I P Pavlova. 2014;64(6):646-59. [Russian]
[20]Youngs RM, Chu MS, Meloni EG, Naydenov A, Carlezon WA Jr, Konradi C. Lithium administration to preadolescent rats causes long-lasting increases in anxiety-like behavior and has molecular consequences. J Neurosci. 2006;26(22):6031-9
[21]Roohbakhsh A, Esmaeili H, Asami Z, Arab Baniasad F, Shamsizadeh A, Rezvani ME. Effect of Anethum graveolens hydroalcoholic extract on pentylenetetrazole-induced paroxysm. Horizon Med Sci. 2013;19(1):41-5. [Persian]
[22]Seghatoleslam M, Alipour F, Shafieian R, Hassanzadeh Z, Edalatmanesh MA, Sadeghnia HR, et al. The effects of Nigella sativa on neural damage after pentylenetetrazole induced seizures in rats. J Tradit Complement Med. 2016;6(3):262-8.
[23]Vafaee F, Hosseini M, Hassanzadeh Z, Edalatmanesh MA, Sadeghnia HR, Seghatoleslam M, et al. The Effects of Nigella Sativa Hydro-alcoholic Extract on Memory and Brain Tissues Oxidative Damage after Repeated Seizures in Rats. Iran J Pharm Res. 2015;14(2):547-57.
[24]Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc. 2007;2(2):322-8.
[25]Murray CL, Obiang P, Bannerman D, Cunningham C. Endogenous IL-1 in Cognitive Function and Anxiety: A Study in IL-1RI−/− Mice. PLoS One. 2013;8(10):e78385.
[26]Kalynchuk LE. Long-term amygdala kindling in rats as a model for the study of interictal emotionality in temporal lobe epilepsy. Neurosci Biobehav Rev. 2000;24(7):691-704.
[27]Milman A, Rosenberg A, Weizman R, Pick CG. Mild traumatic brain injury induces persistent cognitive deficits and behavioral disturbances in mice. J Neurotrauma. 2005;22(9):1003-10.
[28]Mazarati AM, Pineda E, Shin D, Tio D, Taylor AN, Sankar R. Comorbidity between epilepsy and depression: Role of hippocampal interleukin-1beta. Neurobiol Dis. 2010;37(2):461-7.
[29]Jones NC, Cardamone L, Williams JP, Salzberg MR, Myers D, O’Brien TJ. Experimental traumatic brain injury induces a pervasive hyperanxious phenotype in rats. J Neurotrauma. 2008;25(11):1367-74.
[30]Detour J, Schroeder H, Desor D, Nehlig A. A 5-month period of epilepsy impairs spatial memory, decreases anxiety, but spares object recognition in the lithium-pilocarpine model in adult rats. Epilepsia. 2005;46(4):499-508.
[31]Kemppainen EJ, Nissinen J, Pitkänen A. Fear conditioning is impaired in systemic kainic acid and amygdala-stimulation models of epilepsy. Epilepsia. 2006;47(5):820-9.
[32]Jessberger S, Nakashima K, Clemenson GD Jr, Mejia E, Mathews E, Ure K, et al. Epigenetic modulation of seizure-induced neurogenesis and cognitive decline. J Neurosci. 2007;27(22):5967-75.
[33]Chauvière L, Rafrafi N, Thinus-Blanc C, Bartolomei F, Esclapez M, Bernard C. Early deficits in spatial memory and theta rhythm in experimental temporal lobe epilepsy. J Neurosci. 2009;29(17):5402-10.
[34]Kastenberger I, Lutsch C, Herzog H, Schwarzer Ch. Influence of sex and genetic background on anxiety-related and stress-induced behavior of prodynorphin deficient mice. PLoS One. 2012;7(3):e34251.
[35]Leach G, Adidharma W, Yan L. Depression-like responses induced by daytime light deficiency in the diurnal grass rat (Arvicanthis niloticus). Plos One. 2013;8(2):e57115.
[36]Godlevsky LS, Muratova TN, Kresyun NV, van Luijtelaar G, Coenen AM. Anxiolytic and antidepressive effects of electric stimulation of the paleocerebellar cortex in pentylenetetrazol kindled rats. Acta Neurobiol Exp (Wars). 2014;74(4):456-64.
[37]Zárraga-Galindo N, Vergara-Aragón P, Rosales-Meléndez S, Ibarra-Guerrero P, Domínguez-Marrufo LE, Oviedo-García RE, et al. Effects of bee products on pentylenetetrazole-induced seizures in the rat. Proc West Pharmacol Soc. 2011;54:33-40.
[38]Liu ZH, Chuang DM, Smith CB. Lithium ameliorates phenotypic deficits in a mouse model of fragile X syndrome. Int J Neuropsychopharmacol. 2011;14(5):618-30.
[39]Yan XB, Hou HL, Wu LM, Liu J, Zhou JN. Lithium regulates hippocampal neurogenesis by ERK pathway and facilitates recovery of spatial learning and memory in rats after transient global cerebral ischemia. Neuropharmacology. 2007;53(4):487-95.
[40]Chen X, Sun W, Pan Y, Yang Q, Cao K, Zhang J, et al. Lithium ameliorates open-field and elevated plus maze behaviors, and brain phospho-glycogen synthase kinase 3-beta expression in fragile X syndrome model mice. Neurosciences (Riyadh). 2013;18(4):356-62.
[41]Hoeller AA, de Carvalho CR, Franco PLC, Formolo DA, Imthon AK, Dos Santos HR, et al. Behavioral and neurochemical consequences of pentylenetetrazol-induced kindling in young and middle-aged rats. Pharmaceuticals (Basel). 2017;10(3).
[42]Kordi Jaz E, Moghimi A, Fereidoni M, Asadi S, Shamsizadeh A, Roohbakhsh A. SB-334867, an orexin receptor 1 antagonist, decreased seizure and anxiety in pentylenetetrazol-kindled rats. Fundam Clin Pharmacol. 2017;31(2):201-7.
[43]Hashimoto R, Takei N, Shimazu K, Christ L, Lu B, Chuang DM. Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: An essential step for neuroprotection against glutamate excitotoxicity. Neuropharmacology. 2002;43(7):1173-9.
[44]Zhen JL, Chang YN, Qu ZZ, Fu T, Liu JQ, Wang WP. Luteolin rescues pentylenetetrazole-induced cognitive impairment in epileptic rats by reducing oxidative stress and activating PKA/CREB/BDNF signaling. Epilepsy Behav. 2016;57(Pt A):177-84.
[45]Moghadas M, Edalatmanesh MA, Hosseini M. Effect of Lithium Chloride on Serum Levels of BDNF, TNF-α, and Wet Weight of Brain in an Animal Model of Depression. Shefaye Khatam. 2014;2(4):9-19.
[46]Liu ZH, Chuang DM, Beebe Smith C. Lithium ameliorates phenotypic deficits in a mouse model of fragile X syndrome. Int J Neuropsychopharmacol. 2011;14(5):618-30.