Effect Of High Lithium Carbonate Doses On Rat Brain Content Of Some Neurotransmitters
Volume 1 - Issue 5, November 2017 Edition
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Author(s)
Nabil M. Abdel-Hamid, Al-Saffar, MA, Fawzy, MA
Keywords
Lithium carbonate; High doses; Brain tissue; Antidepressant; Experimental study; Bipolar Disorders; Neurotransmitters; Amino acids.
Abstract
We pursued the effect of high doses of lithium carbonate on rat brain neurotransmitters and their precursors, with spot on needed minerals for their synthesis at different periods. The use of high doses of anti depressants, was reported without reference advice, we tried toxic doses (150 mg/kg/d) on four groups of rats, 6/each. They were randomly recruited into, a control group, given only saline by same volume and duration (group 1), acute study, given a single dose, for 2 hours (group 2), sub-acute study group, given a dose each 3 days for 2 weeks (group 3) and a chronic study group, given dose each 3 days for a month (group 4). Brain content of ɣ- aminobutyrate (GABA), glycine, histamine precursor (histidine), dopamine precursors (tyrosine and phenyl alanine), were significantly decreased after 2 hours, 2 weeks and one month of administration, possibly assuming a role of lithium in depression management, with dual role in conversion of these amino acids into protein to maintain tissue integrity. These pathways, may explore better understanding for lithium actions with a non-harmful action of large doses at brain tissue level, apart from extra cranial tissues.
References
[1] Perona MT, Waters S, Hall FS, Sora I, Lesch KP, Murphy DL, et al. Animal models of depression in dopamine, serotonin, and norepinephrine transporter knockout mice: prominent effects of dopamine transporter deletions. Behav Pharmacol 2008;19:566-74.
[2] Smith AJ, Kim SH, Tan J, Sneed KB, Sanberg PR, Borlongan CV, et al. Plasma and Brain Pharmacokinetics of Previously Unexplored Lithium Salts. RSC Adv 2014;4:12362-5.
[3] 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.
[4] Beaulieu JM, Sotnikova TD, Yao WD, Kockeritz L, Woodgett JR, Gainetdinov RR, et al. Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Proc Natl Acad Sci U S A 2004;101:5099-104.
[5] Basselin M, Chang L, Bell JM, Rapoport SI. Chronic lithium chloride administration to unanesthetized rats attenuates brain dopamine D2-like receptor-initiated signaling via arachidonic acid. Neuropsychopharmacology 2005;30:1064-75.
[6] Kulkarni SK, Dhir A. Current investigational drugs for major depression. Expert Opin Investig Drugs 2009;18:767-88.
[7] Scott J, Leboyer M, Hickie I, Berk M, Kapczinski F, Frank E, et al. Clinical staging in psychiatry: a cross-cutting model of diagnosis with heuristic and practical value. Br J Psychiatry 2013;202:243-5.
[8] Hajek T, Cullis J, Novak T, Kopecek M, Blagdon R, Propper L, et al. Brain structural signature of familial predisposition for bipolar disorder: replicable evidence for involvement of the right inferior frontal gyrus. Biol Psychiatry 2013;73:144-52.
[9] Perovic B, Jovanovic M, Miljkovic B, Vezmar S. Getting the balance right: Established and emerging therapies for major depressive disorders. Neuropsychiatr Dis Treat 2010;6:343-64.
[10] Eroglu L, Binyildiz P, Atamer-Simsek S. Lithium-induced changes in the brain levels of free amino acids in stress-exposed rats. Psychopharmacology (Berl) 1980;70:187-9.
[11] 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;161:217-22.
[12] Broderick P, Lynch V. Behavioral and biochemical changes induced by lithium and L-tryptophan in muricidal rats. Neuropharmacology 1982;21:671-9.
[13] Severus E, Taylor MJ, Sauer C, Pfennig A, Ritter P, Bauer M, et al. Lithium for prevention of mood episodes in bipolar disorders: systematic review and meta-analysis. Int J Bipolar Disord 2014;2:15.
[14] Price LH, Heninger GR. Lithium in the treatment of mood disorders. N Engl J Med 1994;331:591-8.
[15] Crossley NA, Bauer M. Acceleration and augmentation of antidepressants with lithium for depressive disorders: two meta-analyses of randomized, placebo-controlled trials. J Clin Psychiatry 2007;68:935-40.
[16] Manji HK, Hsiao JK, Risby ED, Oliver J, Rudorfer MV, Potter WZ. The mechanisms of action of lithium. I. Effects on serotoninergic and noradrenergic systems in normal subjects. Arch Gen Psychiatry 1991;48:505-12.
[17] Muller-Oerlinghausen B, Lewitzka U. Lithium reduces pathological aggression and suicidality: a mini-review. Neuropsychobiology 2010;62:43-9.
[18] Bauer M, Ritter P, Grunze H, Pfennig A. Treatment options for acute depression in bipolar disorder. Bipolar Disord 2012;14 Suppl 2:37-50.
[19] Dixon JF, Hokin LE. Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex. Proc Natl Acad Sci U S A 1998;95:8363-8.
[20] Bauer M, Alda M, Priller J, Young LT. Implications of the neuroprotective effects of lithium for the treatment of bipolar and neurodegenerative disorders. Pharmacopsychiatry 2003;36 Suppl 3:S250-4.
[21] Malhi GS, Tanious M, Das P, Coulston CM, Berk M. Potential mechanisms of action of lithium in bipolar disorder. Current understanding. CNS Drugs 2013;27:135-53.
[22] Perova T, Kwan M, Li PP, Warsh JJ. Differential modulation of intracellular Ca2+ responses in B lymphoblasts by mood stabilizers. Int J Neuropsychopharmacol 2010;13:693-702.
[23] Emamghoreishi M, Schlichter L, Li PP, Parikh S, Sen J, Kamble A, et al. High intracellular calcium concentrations in transformed lymphoblasts from subjects with bipolar I disorder. Am J Psychiatry 1997;154:976-82.
[24] Dhawan D, Singh A, Singh B, Bandhu HK, Chand B, Singh N. Effect of lithium augmentation on the trace elemental profile in diabetic rats. Biometals 1999;12:375-81.
[25] Walton NY, Gunawan S, Treiman DM. Brain amino acid concentration changes during status epilepticus induced by lithium and pilocarpine. Exp Neurol 1990;108:61-70.
[26] Parrot JL, Tuchmann Duplessis M, Laborde C. [Modification of the histaminopexic power of blood serum in rats under the influence of sex hormones]. J Physiol (Paris) 1957;49:333-5.
[27] Schlumpf M, Lichtensteiger W, Langemann H, Waser PG, Hefti F. A fluorometric micromethod for the simultaneous determination of serotonin, noradrenaline and dopamine in milligram amounts of brain tissue. Biochem Pharmacol 1974;23:2437-46.
[28] Gindler EM, King JD. Rapid colorimetric determination of calcium in biologic fluids with methylthymol blue. Am J Clin Pathol 1972;58:376-82.
[29] Neill DW, Neely RA. The estimation of magnesium in serum using titan yellow. J Clin Pathol 1956;9:162-3.
[30] Johnston-Wilson NL, Sims CD, Hofmann JP, Anderson L, Shore AD, Torrey EF, et al. Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. The Stanley Neuropathology Consortium. Mol Psychiatry 2000;5:142-9.
[31] Whittle N, Li L, Chen WQ, Yang JW, Sartori SB, Lubec G, et al. Changes in brain protein expression are linked to magnesium restriction-induced depression-like behavior. Amino Acids 2011;40:1231-48.
[32] Machado-Vieira R, Manji HK, Zarate CA, Jr. The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar Disord 2009;11 Suppl 2:92-109.
[33] Rao TS, Asha MR, Ramesh BN, Rao KS. Understanding nutrition, depression and mental illnesses. Indian J Psychiatry 2008;50:77-82.
[34] Moffett JR, Ross B, Arun P, Madhavarao CN, Namboodiri AM. N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol 2007;81:89-131.
[35] Yudkoff M, Daikhin Y, Melo TM, Nissim I, Sonnewald U, Nissim I. The ketogenic diet and brain metabolism of amino acids: relationship to the anticonvulsant effect. Annu Rev Nutr 2007;27:415-30.
[36] Nag M, Guha SR, Turner AJ. Inhibition of glutaminase activity of rat brain by lithium. Biochem Pharmacol 1983;32:1798-800.
[37] Hajek T, Bauer M, Simhandl C, Rybakowski J, O'Donovan C, Pfennig A, et al. Neuroprotective effect of lithium on hippocampal volumes in bipolar disorder independent of long-term treatment response. Psychol Med 2014;44:507-17.
[38] Abu Shmais GA, Al-Ayadhi LY, Al-Dbass AM, El-Ansary AK. Mechanism of nitrogen metabolism-related parameters and enzyme activities in the pathophysiology of autism. J Neurodev Disord 2012;4:4.
[39] Chen G, Yuan PX, Jiang YM, Huang LD, Manji HK. Lithium increases tyrosine hydroxylase levels both in vivo and in vitro. J Neurochem 1998;70:1768-71.
[40] Sparapani M, Virgili M, Ortali F, Contestabile A. Effects of chronic lithium treatment on ornithine decarboxylase induction and excitotoxic neuropathology in the rat. Brain Res 1997;765:164-8.
[41] Kasuya J, Kaas G, Kitamoto T. Effects of lithium chloride on the gene expression profiles in Drosophila heads. Neurosci Res 2009;64:413-20.
[42] Chiu CT, Wang Z, Hunsberger JG, Chuang DM. Therapeutic potential of mood stabilizers lithium and valproic acid: beyond bipolar disorder. Pharmacol Rev 2013;65:105-42.
[43] Awad SS, Miskulin J, Thompson N. Parathyroid adenomas versus four-gland hyperplasia as the cause of primary hyperparathyroidism in patients with prolonged lithium therapy. World J Surg 2003;27:486-8.
[44] Lau K, Goldfarb S, Grabie M, Agus ZS, Goldberg M. Mechanism of lithium-induced hypercalciuria in rats. Am J Physiol 1978;234:E294-300.
[45] Rizwan MM, Perrier ND. Long-term lithium therapy leading to hyperparathyroidism: a case report. Perspect Psychiatr Care 2009;45:62-5.
[46] Eby GA, Eby KL. Rapid recovery from major depression using magnesium treatment. Med Hypotheses 2006;67:362-70.
[47] Szewczyk B, Poleszak E, Sowa-Kucma M, Siwek M, Dudek D, Ryszewska-Pokrasniewicz B, et al. Antidepressant activity of zinc and magnesium in view of the current hypotheses of antidepressant action. Pharmacol Rep 2008;60:588-9.
[48] Dell'Osso L, Del Grande C, Gesi C, Carmassi C, Musetti L. A new look at an old drug: neuroprotective effects and therapeutic potentials of lithium salts. Neuropsychiatr Dis Treat 2016;12:1687-703.
[49] Brosnan JT, Brosnan ME. The sulfur-containing amino acids: an overview. J Nutr 2006;136:1636S-40S.
Author profile
Nabil Mohie Abdel–Hamid.
Professor of Cancer Biology at Department of Biochemistry, Ex- and First Dean and Founder of Faculty of Pharmacy, Kafrelsheikh University, Egypt. Had his Master in Biochemistry by 1989, and his PhD in biochemistry by 1999. Member of The Higher Consulting Organization of Egyptian Scientists Council. Deputy of Director of: The Egyptian Association of Cancer Research. Member in: The Arab Evaluators for Scientific Degree Promotions for Professorships. Member in: The Egyptian Evaluators for Scientific Degree Promotions for both associate and full Professorships. Research Interest: Cancer Biology, Principal Instructor and interested in Hepatocellular Carcinoma Research(Both Early Detection, Looking for New Sensitive and Specific Markers and Therapeutic Perusal), as New Trends in Management of Hepatocellular Carcinoma, Including Chemo and Radio Sensitization to Cancer Therapy. After long time of studying cell membrane, we now work on targeting liver cancer cell through membrane protein leads to minimize side effects, dose burdens, and treatment durations, with a maximal efficacy.
