Brain arachidonic acid uptake and turnover: Implications for signaling and bipolar disorder

Current Opinion in Clinical Nutrition and Metabolic Care

Volumn 13, Issue 2, 2010, Pages 130-138

  Duncan, Robin E ^a   Bazinet, Richard P ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

Adipose; Arachidonic acid; Bipolar disorder; Brain; Signaling

Indexed keywords

ACYLGLYCEROL LIPASE; AMFEBUTAMONE; AMPHETAMINE; ARACHIDONIC ACID; CARBAMAZEPINE; DOCOSAHEXAENOIC ACID; FLUOXETINE; HORMONE SENSITIVE LIPASE; ICOSAPENTAENOIC ACID; IMIPRAMINE; LAMOTRIGINE; LINOLENIC ACID; LITHIUM; OMEGA 6 FATTY ACID; PHOSPHOLIPASE A2; PHOSPHOLIPID; PLACEBO; QUINPIROLE; TOPIRAMATE; VALPROIC ACID;

ADIPOSE TISSUE; ARACHIDONIC ACID METABOLISM; BIPOLAR DEPRESSION; BIPOLAR DISORDER; BRAIN FUNCTION; BRAIN LEVEL; CLINICAL TRIAL; DIETARY INTAKE; DRUG MECHANISM; ENCEPHALITIS; ESTERIFICATION; EXCITOTOXICITY; FATTY ACID BLOOD LEVEL; FATTY ACID OXIDATION; FOOD COMPOSITION; HUMAN; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; TURNOVER TIME;

ANIMALS; ANTIMANIC AGENTS; ARACHIDONIC ACID; BIPOLAR DISORDER; BRAIN; HUMANS; PHOSPHOLIPASES A2; PHOSPHOLIPIDS; SIGNAL TRANSDUCTION;

RODENTIA;

EID: 76749098860     PISSN: 13631950     EISSN: 14736519     Source Type: Journal    
DOI: 10.1097/MCO.0b013e328336b615     Document Type: Review

References (114)

1. Aaes-Jørgensen E. Essential fatty acids. Physiol Rev 1961; 41:1-51.
2. Salem N Jr, Pawlosky R, Wegher B, Hibbeln J. In vivo conversion of linoleic acid to arachidonic acid in human adults. Prostaglandins Leukot Essent Fatty Acids 1999; 60:407-410.
3. Su HM, Corso TN, Nathanielsz PW, Brenna JT. Linoleic acid kinetics and conversion to arachidonic acid in the pregnant and fetal baboon. J Lipid Res 1999; 40:1304-1312.
4. Farquharson J, Cockburn F, Patrick WA, et al. Infant cerebral cortex phos-pholipid fatty-acid composition and diet. Lancet 1992; 340:810-813.
5. Makrides M, Neumann MA, Byard RW, et al. Fatty acid composition of brain, retina, and erythrocytes in breast-and formula-fed infants. Am J Clin Nutr 1994; 60:189-194.
6. Cunnane SC. Problems with essential fatty acids: time for a new paradigm? Prog Lipid Res 2003; 42:544-568.
7. Cunnane SC. The long history of essential fatty acids but belated knowledge about linoleate deficiency per se: a paradox. J Nutr 1999; 129:446.
8. Mohrhauer H, Holman RT. The effect of dose level of essential fatty acids upon fatty acid composition of the rat liver. J Lipid Res 1963; 4:151-159.
9. Stroud CK, Nara TY, Roqueta-Rivera M, et al. Disruption of FADS2 gene in mice impairs male reproduction and causes dermal and intestinal ulceration. J Lipid Res 2009.
10. Cunnane SC, Anderson MJ. The majority of dietary linoleate in growing rats is beta-oxidized or stored in visceral fat. J Nutr 1997; 127:146-152.
11. Lefkowitz W, Lim SY, Lin Y, Salem N Jr. Where does the developing brain obtain its docosahexaenoic acid? Relative contributions of dietary alpha-linolenic acid, docosahexaenoic acid, and body stores in the developing rat. Pediatr Res 2005; 57:157-165.
12. Duncan RE, Ahmadian M, Jaworski K, et al. Regulation of lipolysis in adipocytes. Annu Rev Nutr 2007; 27:79-101.
13. Kalderon B, Mayorek N, Berry E, et al. Fatty acid cycling in the fasting rat. Am J Physiol Endocrinol Metab 2000; 279:E221-E227.
14. Fickova M, Hubert P, Cremel G, Leray C. Dietary (n-3) and (n-6) polyunsa-turated fatty acids rapidly modify fatty acid composition and insulin effects in rat adipocytes. J Nutr 1998; 128:512-519.
15. Raclot T, Holm C, Langin D. Fatty acid specificity of hormone-sensitive lipase. Implication in the selective hydrolysis of triacylglycerols. J Lipid Res 2001; 42:2049-2057.
16. Zimmermann R, Strauss JG, Haemmerle G, et al. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 2004; 306:1383-1386.
17. Jenkins CM, Mancuso DJ, Yan W, et al. Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol trans-acylase activities. J Biol Chem 2004; 279:48968-48975.
18. Villena JA, Roy S, Sarkadi-Nagy E, et al. Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. J Biol Chem 2004; 279:47066-47075.
19. Karlsson M, Contreras JA, Hellman U, et al. cDNA cloning, tissue distribution, and identification of the catalytic triad of monoglyceride lipase. Evolutionary relationship to esterases, lysophospholipases, and haloperoxidases. J Biol Chem 1997; 272:27218-27223.
20. Raclot T, Langin D, Lafontan M, Groscolas R. Selective release of human adipocyte fatty acids according to molecular structure. Biochem J 1997; 324 (Pt 3):911-915.
21. Edmond J. Essential polyunsaturated fatty acids and the barrier to the brain: the components of a model for transport. J Mol Neurosci 2001; 16:181-193; discussion 215-221
22. Thies F, Delachambre MC, Bentejac M, et al. Unsaturated fatty acids esterified in 2-acyl-l-lysophosphatidylcholine bound to albumin are more efficiently taken up by the young rat brain than the unesterified form. J Neurochem 1992; 59:1110-1116.
23. Robinson PJ, Noronha J, DeGeorge JJ, et al. A quantitative method for measuring regional in vivo fatty-acid incorporation into and turnover within brain phospholipids: review and critical analysis. Brain Res Brain Res Rev 1992; 17:187-214.
24. Chen CT, Ma DW, Kim JH, et al. The low density lipoprotein receptor is not necessary for maintaining mouse brain polyunsaturated fatty acid concentrations. J Lipid Res 2008; 49:147-152.
25. Rahman T, Taha AY, Song BJ, et al. The very low density lipoprotein receptor is not necessary for maintaining brain polyunsaturated fatty acid concentrations. Prostaglandins Leukot Essent Fatty Acids (in press).
26. Rapoport SI, Chang MC, Spector AA. Delivery and turnover of plasma-derived essential PUFAs in mammalian brain. J Lipid Res 2001; 42:678-685.
27. Chen CT, Green JT, Orr SK, Bazinet RP. Regulation of brain polyunsaturated fatty acid uptake and turnover. Prostaglandins Leukot Essent Fatty Acids 2008; 79:85-91.
28. Contreras MA, Chang MC, Rosenberger TA, et al. Chronic nutritional deprivation of n-3 alpha-linolenic acid does not affect n-6 arachidonic acid recycling within brain phospholipids of awake rats. J Neurochem 2001; 79:1090-1099.
29. Green JT, Liu Z, Bazinet RP. Brain phospholipid arachidonic acid half lives are not altered following 15 weeks of n-3 polyunsaturated fatty acid adequate ordeprived diet. J Lipid Res 2009.
30. Demar JC Jr, Lee HJ, Chang L, et al. Brain elongation of linoleic acid is a negligible source of the arachidonate in brain phospholipids of adult rats. Biochim Biophys Acta 2006; 1761:1050-1059.
31. Diau GY, Hsieh AT, Sarkadi-Nagy EA, et al. The influence of long chain polyunsaturate supplementation on docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system. BMC Med 2005; 3:11.
32. Demar JC Jr, Ma K, Chang L, et al. alpha-Linolenic acid does not contribute appreciably to docosahexaenoic acid within brain phospholipids of adult rats fed a diet enriched in docosahexaenoic acid. J Neurochem 2005; 94:1063-1076.
33. Golovko MY, Murphy EJ. Uptake and metabolism of plasma-derived erucic acid by rat brain. J Lipid Res 2006; 47:1289-1297.
34. Chen CT, Liu Z, Ouellet M, et al. Rapid beta-oxidation of eicosapentaenoic acid in mouse brain: an in situ study. Prostaglandins Leukot Essent Fatty Acids 2009; 80:157-163.
35. Ouellet M, Emond V, Chen CT, et al. Diffusion of docosahexaenoic and eicosapentaenoic acids through the blood-brain barrier: an in situ cerebralperfusion study. Neurochem Int 2009; 55:476-482.
36. Cunnane SC, Ryan MA, Nadeau CR, et al. Why is carbon from some polyunsaturates extensively recycled into lipid synthesis? Lipids 2003; 38:477-484.
37. Wijendran V, Lawrence P, Diau GY, et al. Significant utilization of dietary arachidonic acid is for brain adrenic acid in baboon neonates. J Lipid Res 2002; 43:762-767.
38. Green JT, Orr SK, Bazinet RP. The emerging role of group VI calcium-independent phospholipase A2 in releasing docosahexaenoic acid from brain phospholipids. J Lipid Res 2008; 49:939-944.
39. Lands WEM, Crawford CG. Enzymes of membrane phospholipid metabolism. New York: Plenum; 1976. pp. 3-85.
40. Bazinet RP. Is the brain arachidonic acid cascade a common target of drugs used to manage bipolar disorder? Biochem Soc Trans 2009; 37:1104-1109.
41. Bazan NG. Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer's disease. J Lipid Res 2009; 50 (Suppl):S400-S405.
42. Orr SK, Bazinet RP. The emerging role of docosahexaenoic acid in neuroin-flammation. Curr Opin Investig Drugs 2008; 9:735-743.
43. Bosetti F. Arachidonic acid metabolism in brain physiology and pathology: lessons from genetically altered mouse models. J Neurochem 2007; 102:577-586.
44. Axelrod J. Receptor-mediated activation of phospholipase A2 and arachidonic acid release in signal transduction. Biochem Soc Trans 1990; 18:503-507.
45. Felder CC, Williams HL, Axelrod J. A transduction pathway associated with receptors coupled to the inhibitory guanine nucleotide binding protein Gi that amplifies ATP-mediated arachidonic acid release. Proc Natl Acad Sci USA 1991; 88:6477-6480.
46. Rapoport SI. In vivo approaches to quantifying and imaging brain arachidonic and docosahexaenoic acid metabolism. J Pediatr 2003; 143:S26-34.
47. Felder CC, Kanterman RY, Ma AL, Axelrod J. Serotonin stimulates phospholipase A2 and the release of arachidonic acid in hippocampal neurons by a type 2 serotonin receptor that is independent of inositolphospholipid hydrolysis. Proc Natl Acad Sci USA 1990; 87:2187-2191.
48. Dumuis A, Sebben M, Haynes L, et al. NMDA receptors activate the arachidonic acid cascade system in striatal neurons. Nature 1988; 336:68-70.
49. Piomelli D, Pilon C, Giros B, et al. Dopamine activation of the arachidonic acid cascade as a basis for D1/D2 receptor synergism. Nature 1991; 353:164-167.
50. Vial D, Piomelli D. Dopamine D2 receptors potentiate arachidonate release via activation of cytosolic, arachidonate-specific phospholipase A2. J Neurochem 1995; 64:2765-2772.
51. Rapoport SI, Purdon D, Shetty HU, et al. In vivo imaging of fatty acid incorporation into brain to examine signal transduction and neuroplasticity involving phospholipids. Ann N Y Acad Sci 1997; 820:56-73; discussion 73-74
52. Bhattacharjee AK, Chang L, Lee HJ, et al. D2 but not D1 dopamine receptor stimulation augments brain signaling involving arachidonic acid in unanesthe-tized rats. Psychopharmacology (Berl) 2005; 180:735-742.
53. Bhattacharjee AK, Chang L, White L, et al. Imaging apomorphine stimulation of brain arachidonic acid signaling via D2-like receptors in unanesthetized rats. Psychopharmacology (Berl) 2008; 197:557-566.
54. Bhattacharjee AK, Chang L, White L, et al. D-Amphetamine stimulates D(2) dopamine receptor-mediated brain signaling involving arachidonic acid in unanesthetized rats. J Cereb Blood Flow Metab 2006.
55. Basselin M, Chang L, Seemann R, et al. Chronic lithium administration potentiates brain arachidonic acid signaling at rest and during cholinergic activation in awake rats. J Neurochem 2003; 85:1553-1562.
56. Basselin M, Villacreses NE, Chen M, et al. Chronic carbamazepine administration reduces N-methyl-D-aspartate receptor-initiated signaling via arachidonic acid in rat brain. Biol Psychiatry 2007; 62:934-943.
57. Qu Y, Chang L, Klaff J, et al. Imaging brain phospholipase A2 activation in awake rats in response to the 5-HT2A/2C agonist (+/\-)2,5-dimethoxy-4- iodophenyl-2-aminopropane (DOI). Neuropsychopharmacology 2003; 28:244-252.
58. Qu Y, Villacreses N, Murphy DL, Rapoport SI. 5-HT2A/2C receptor signaling via phospholipase A2 and arachidonic acid is attenuated in mice lacking the serotonin reuptake transporter. Psychopharmacology (Berl) 2005; 180:12-20.
59. Basselin M, Villacreses N, Lee HJ, et al. Chronic lithium administration attenuates upregulated brain arachidonic acid metabolism in a rat model of neuroinflammation. J Neurochem 2007; 102:761-772.
60. Lee H, Villacreses NE, Rapoport SI, Rosenberger TA. In vivo imaging detects a transient increase in brain arachidonic acid metabolism: a potential marker of neuroinflammation. J Neurochem 2004; 91:936-945.
61. Rintala J, Seemann R, Chandrasekaran K, et al. 85 kDa cytosolic phospholipase A2 is a target for chronic lithium in rat brain. Neuroreport 1999; 10:3887-3890.
62. Chang MC, Jones CR. Chronic lithium treatment decreases brain phospholipase A2 activity. Neurochem Res 1998; 23:887-892.
63. Basselin M, Chang L, Bell JM, Rapoport SI. Chronic lithium chloride administration attenuates brain NMDA receptor-initiated signaling via arachidonic acid in unanesthetized rats. Neuropsychopharmacology 2006; 31:1659-1674.
64. 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; 30:1064-1075. (Pubitemid 40720964)
65. Basselin M, Chang L, Seemann R, et al. Chronic lithium administration to rats selectively modifies 5-HT2A/2C receptor-mediated brain signaling via arachidonic acid. Neuropsychopharmacology 2005; 30:461-472.
66. Channing MA, Simpson N. Radiosynthesis of 1-[11C]polyhomoallylic fatty acids. J Labelled Compds Radiopharm 1993; 3:541-546.
67. Chang MC, Arai T, Freed LM, et al. Brain incorporation of [1-11C]arachi-donate in normocapnic and hypercapnic monkeys, measured with positron emission tomography. Brain Res 1997; 755:74-83.
68. Giovacchini G, Chang MC, Channing MA, et al. Brain incorporation of [11C]arachidonic acid in young healthy humans measured with positron emission tomography. J Cereb Blood Flow Metab 2002; 22:1453-1462.
69. Giovacchini G, Lerner A, Toczek MT, et al. Brain incorporation of 11C-arachidonic acid, blood volume, and blood flow in healthy aging: a study with partial-volume correction. J Nucl Med 2004; 45:1471-1479.
70. Esposito G, Giovacchini G, Der M, et al. Imaging signal transduction via arachidonic acid in the human brain during visual stimulation, by means of positron emission tomography. Neuroimage 2007; 34:1342-1351.
71. Esposito G, Giovacchini G, Liow JS, et al. Imaging neuroinflammation in Alzheimer's disease with radiolabeled arachidonic acid and PET. J Nucl Med 2008; 49:1414-1421.
72. Williams RS. Employing multiple models, methods and mechanisms in bipolar disorder research. Biochem Soc Trans 2009; 37:1077-1079.
73. Purcell SM, Wray NR, Stone JL, et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009; 460:748-752.
74. Beaulieu JM, Marion S, Rodriguiz RM, et al. A beta-arrestin 2 signaling complex mediates lithium action on behavior. Cell 2008; 132:125-136.
75. Williams RS, Cheng L, Mudge AW, Harwood AJ. A common mechanism of action for three mood-stabilizing drugs. Nature 2002; 417:292-295.
76. Beneyto M, Kristiansen LV, Oni-Orisan A, et al. Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Neuropsychopharmacology 2007; 32:1888-1902.
77. Mueller HT, Meador-Woodruff JH. NR3A NMDA receptor subunit mRNA expression in schizophrenia, depression and bipolar disorder. Schizophr Res 2004; 71:361-370.
78. Harwood AJ, Agam G. Search for a common mechanism of mood stabilizers. Biochem Pharmacol 2003; 66:179-189.
79. Berridge MJ, Downes CP, Hanley MR. Neural and developmental actions of lithium: a unifying hypothesis. Cell 1989; 59:411-419.
80. Gould TD, Manji HK. Glycogen synthase kinase-3: a putative molecular target for lithium mimetic drugs. Neuropsychopharmacology 2005; 30:1223-1237.
81. Gould TD, Manji HK. Signaling networks in the pathophysiology and treatment of mood disorders. J Psychosom Res 2002; 53:687-697.
82. Manji HK, Bersudsky Y, Chen G, et al. Modulation of protein kinase C isozymes and substrates by lithium: the role of myo-inositol. Neuropsychopharmacology 1996; 15:370-381.
83. Manji HK, Chen G. PKC, MAP kinases and the bcl-2 family of proteins as long-term targets for mood stabilizers. Mol Psychiatry 2002; 7 (Suppl 1): S46-S56.
84. Rao JS, Lee HJ, RapoportSI, Bazinet RP. Mode of action of mood stabilizers: is the arachidonic acid cascade a common target? Mol Psychiatry 2008;13:585-596.
85. Rapoport SI, Bosetti F. Do lithium and anticonvulsants target the brain arachidonic acid cascade in bipolar disorder? Arch Gen Psychiatry 2002; 59:592-596.
86. Chang MC, Grange E, Rabin O, et al. Lithium decreases turnover of arachidonate in several brain phospholipids. Neurosci Lett 1996; 220:171-174.
87. Chang MC, Bell JM, Purdon AD, et al. Dynamics of docosahexaenoic acid metabolism in the central nervous system: lack of effect of chronic lithium treatment. Neurochem Res 1999; 24:399-406.
88. Leslie CC. Regulation of the specific release of arachidonic acid by cytosolic phospholipase A2. Prostaglandins Leukot Essent Fatty Acids 2004; 70:373-376.
89. Alonso F, Henson PM, Leslie CC. A cytosolic phospholipase in human neutrophils that hydrolyzes arachidonoyl-containing phosphatidylcholine. Biochim Biophys Acta 1986; 878:273-280.
90. Watson DG, Lenox RH. Chronic lithium-induced down-regulation of MARCKS in immortalized hippocampal cells: potentiation by muscarinic receptor activation. J Neurochem 1996; 67:767-777.
91. Rao JS, Rapoport SI, Bosetti F. Decrease in the AP-2 DNA-binding activity and in the protein expression of AP-2 alpha and AP-2 beta in frontal cortex of rats treated with lithium for 6 weeks. Neuropsychopharmacology 2005; 30:2006-2013.
92. Bosetti F, Rintala J, Seemann R, et al. Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E(2) concentration in rat brain. Mol Psychiatry 2002; 7:845-850.
93. Chang MC, ContrerasMA, RosenbergerTA, etal. Chronic valproate treatment decreases the in vivo turnover of arachidonic acid in brain phospholipids: a possible common effect of mood stabilizers. J Neurochem 2001; 77:796-803.
94. Bazinet RP, Rao JS, Chang L, et al. Chronic valproate does not alter the kinetics of docosahexaenoic acid within brain phospholipids of the una-nesthetized rat. Psychopharmacology (Berl) 2005; 182:180-185. (Pubitemid 41400875)
95. Bosetti F, Weerasinghe GR, Rosenberger TA, Rapoport SI. Valproic acid down-regulates the conversion of arachidonic acid to eicosanoids via cyclooxygenase-1 and-2 in rat brain. J Neurochem 2003; 85:690-696.
96. Rao JS, Bazinet RP, Rapoport SI, Lee HJ. Chronic treatment of rats with sodium valproate downregulates frontal cortex NF-kB DNA binding activity and COX-2 mRNA. Bipolar Disord 2007; 9:513-520.
97. Bazinet RP, Weis MT, Rapoport SI, Rosenberger TA. Valproic acid selectively inhibits conversion of arachidonic acid to arachidonoyl-CoA by brain microsomal long-chain fatty acyl-CoA synthetases: relevance to bipolar disorder. Psychopharmacology (Berl) 2006; 184:122-129.
98. Bazinet RP, Rao JS, Chang L, et al. Chronic carbamazepine decreases the incorporation rate and turnover of arachidonic acid but not docosahexaenoic acid in brain phospholipids of the unanesthetized rat: relevance to bipolar disorder. Biol Psychiatry 2006; 59:401-407.
99. Ghelardoni S, Tomita YA, Bell JM, et al. Chronic carbamazepine selectively downregulates cytosolic phospholipase A2 expression and cyclooxygenase activity in rat brain. Biol Psychiatry 2004; 56:248-254.
100. Rao JS, Bazinet RP, Rapoport SI, Lee HJ. Chronic administration of carbamazepine downregulates AP-2 DNA binding activity and AP-2a protein expression in rat frontal cortex. Biol Psychiatry 2007; 61:154-161.
101. Gijsman HJ, Geddes JR, Rendell JM, et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry 2004; 161:1537-1547.
102. Radin NS. Extraction of tissue lipids with a solvent of low toxicity. Methods Enzymol 1981; 72:5-7.
103. Rao JS, Ertley RN, Lee HJ, et al. Chronic fluoxetine upregulates activity, protein and mRNA levels of cytosolic phospholipase A2 in rat frontal cortex. Pharmacogenomics J 2006; 6:413-420.
104. Lee HJ, Rao JS, Chang L, et al. Chronic imipramine but not bupropion increases arachidonic acid signaling in rat brain: is this related to 'switching' in bipolar disorder? Mol Psychiatry 2008.
105. Bowden CL, Calabrese JR, Sachs G, et al. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Arch Gen Psychiatry 2003; 60:392-400. (Pubitemid 36403000)
106. Lee HJ, Ertley RN, Rapoport SI, etal. Chronic administration of lamotrigine downregulates COX-2 mRNA and protein in rat frontal cortex. Neurochem Res 2008; 33:861-866.
107. Lee HJ, Rao JS, Chang L, et al. Chronic lamotrigine does not alter the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat: implications for the treatment of bipolar disorder. Psychopharmacology (Berl) 2007; 193:467-474.
108. Shaldubina A, Einat H, Szechtman H, et al. Preliminary evaluation of oral anticonvulsant treatment in the quinpirole model of bipolar disorder. J Neural Transm 2002; 109:433-440.
109. Calabrese JR, Keck PE Jr, McElroy SL, Shelton MD. A pilot study of topiramate as monotherapy in the treatment of acute mania. J Clin Psycho-pharmacol 2001; 21:340-342.
110. McElroy SL, SuppesT, KeckPE, etal. Open-label adjunctive topiramate in the treatment of bipolar disorders. Biol Psychiatry 2000; 47:1025-1033.
111. Vieta E, Sanchez-Moreno J, Goikolea JM, et al. Adjunctive topiramate in bipolar II disorder. World J Biol Psychiatry 2003; 4:172-176.
112. Ghelardoni S, Bazinet RP, Rapoport SI, Bosetti F. Topiramate does not alter expression in rat brain of enzymes of arachidonic acid metabolism. Psychopharmacology (Berl) 2005; 180:523-529.
113. Lee HJ, Ghelardoni S, Chang L, etal. Topiramate does not alter the kinetics of arachidonic or docosahexaenoic acid in brain phospholipids of the unanesthetized rat. Neurochem Res 2005; 30:677-683. (Pubitemid 41199686)
114. Kushner SF, Khan A, Lane R, Olson WH. Topiramate monotherapy in the management of acute mania: results of four double-blind placebo-controlled trials. Bipolar Disord 2006; 8:15-27.