Skip to main content
SpringerLink
Log in

Tamoxifen use for the management of mania: a review of current preclinical evidence

  • Review
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Preliminary data on the efficacy of tamoxifen in reducing manic symptoms of bipolar disorder (BD) suggest that this agent may be a potential treatment for the management of this psychiatric disorder. However, the antimanic properties of tamoxifen have not been fully elucidated, hampering the development and/or use of mood-stabilising drugs that may share its same therapeutic mechanisms of action. Notably, we may gain a greater understanding of the neurobiological and therapeutic properties of tamoxifen by using suitable animal models of mania.

Objectives

Here, we review the preclinical studies that have evaluated the effects of tamoxifen to provide an overview of the current progress in our understanding of its antimanic actions, highlighting the critical role of protein kinase C (PKC) as a therapeutic target for the treatment of BD.

Conclusions

To date, this field has struggled to make significant progress, and the organisation of an explicit battery of tests is a valuable tool for assessing a number of prominent facets of BD, which may provide a greater understanding of the entire scope of this disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abrial E, Etievant A, Bétry C, Scarna H, Lucas G, Haddjeri N, Lambás-Señas L (2012) Protein kinase C regulates mood-related behaviors and adult hippocampal cell proliferation in rats. Prog Neuropsychopharmacol Biol Psychiatry 43C:40–48

    Google Scholar 

  • Aksoy E, Goldman M, Willems F (2004) Protein kinase C epsilon: a new target to control inflammation and immune-mediated disorders. Int J Biochem Cell Biol 36:183–8

    CAS  PubMed  Google Scholar 

  • Alda M, Hajek T, Calkin C, O'Donovan C (2009) Treatment of bipolar disorder: new perspectives. Ann Med 41:186–96

    CAS  PubMed  Google Scholar 

  • American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Publishing, Washington, DC

    Google Scholar 

  • Amrollahi Z, Rezaei F, Salehi B, Modabbernia AH, Maroufi A, Esfandiari GR, Naderi M, Ghebleh F, Ahmadi-Abhari SA, Sadeghi M, Tabrizi M, Akhondzadeh S (2011) Double-blind, randomized, placebo-controlled 6-week study on the efficacy and safety of the tamoxifen adjunctive to lithium in acute bipolar mania. J Affect Disord 129:327–31

    CAS  PubMed  Google Scholar 

  • Andreatini R (2002) A importância dos modelos animais em psiquiatria. Rev Bras Psiquiatr 24:164

    Google Scholar 

  • Andreatini R, Lacerda R, Vital M (2006) Modelos animais em psicofarmacologia. In: Almeida R (ed) Psicofarmacologia: fundamentos práticos. Guanabara-Koogan, Rio de Janeiro, pp 53–61

    Google Scholar 

  • Armani F, Andersen ML, Andreatini R, Frussa-Filho R, Tufik S, Galduróz JC (2012) Successful combined therapy with tamoxifen and lithium in a paradoxical sleep deprivation-induced mania model. CNS Neurosci Ther 18:119–25

    CAS  PubMed  Google Scholar 

  • Barbini B, Bertelli S, Colombo C, Smeraldi E (1996) Sleep loss, a possible factor in augmenting manic episode. Psychiatry Res 65:121–5

    CAS  PubMed  Google Scholar 

  • Basu A, Pal D (2010) Two faces of protein kinase Cδ: the contrasting roles of PKCδ in cell survival and cell death. Sci World J 10:2272–84

    CAS  Google Scholar 

  • Baum AE, Akula N, Cabanero M, Cardona I, Corona W, Klemens B, Schulze TG, Cichon S, Rietschel M, Nothen MM, Georgi A, Schumacher J, Schwarz M, Abou Jamra R, Hofels S, Propping P, Satagopan J, Detera-Wadleigh SD, Hardy J, McMahon FJ (2008) A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry 13:197–207

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bebchuk JM, Arfken CL, Dolan-Manji S, Murphy J, Hasanat K, Manji HK (2000) A preliminary investigation of a protein kinase C inhibitor in the treatment of acute mania. Arch Gen Psychiatry 57:95–7

    CAS  PubMed  Google Scholar 

  • Becker JB, Snyder PJ, Miller MM, Westgate SA, Jenuwine MJ (1987) The influence of estrous cycle and intrastriatal estradiol on sensorimotor performance in the female rat. Pharmacol Biochem Behav 27:53–9

    CAS  PubMed  Google Scholar 

  • Benedetti F, Fresi F, Maccioni P, Smeraldi E (2008) Behavioural sensitization to repeated sleep deprivation in a mice model of mania. Behav Brain Res 187:221–7

    PubMed  Google Scholar 

  • Benes FM, Kwok EW, Vincent SL, Todtenkopf MS (1998) A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives. Biol Psychiatry 44:88–97

    CAS  PubMed  Google Scholar 

  • Birnbaum SG, Yuan PX, Wang M, Vijayraghavan S, Bloom AK, Davis DJ, Gobeske KT, Sweatt JD, Manji HK, Arnsten AF (2004) Protein kinase C overactivity impairs prefrontal cortical regulation of working memory. Science 306:882–4

    CAS  PubMed  Google Scholar 

  • Bitran JA, Potter WZ, Manji HK, Gusovsky F (1990) Chronic Li+ attenuates agonist- and phorbol ester-mediated Na+/H+ antiporter activity in HL-60 cells. Eur J Pharmacol 188:193–202

    Google Scholar 

  • Browman KE, Kantor L, Richardson S, Badiani A, Robinson TE, Gnegy ME (1998) Injection of the protein kinase C inhibitor Ro31-8220 into the nucleus accumbens attenuates the acute response to amphetamine: tissue and behavioral studies. Brain Res 814:112–9

    CAS  PubMed  Google Scholar 

  • Burdick KE, Braga RJ, Goldberg JF, Malhotra AK (2007) Cognitive dysfunction in bipolar disorder: future place of pharmacotherapy. CNS Drugs 21:971–81

    CAS  PubMed  Google Scholar 

  • Burguillos MA, Deierborg T, Kavanagh E, Persson A, Hajji N, Garcia-Quintanilla A, Cano J, Brundin P, Englund E, Venero JL, Joseph B (2011) Caspase signalling controls microglia activation and neurotoxicity. Nature 472:319–24

    CAS  PubMed  Google Scholar 

  • Burrows KB, Gudelsky G, Yamamoto BK (2000) Rapid and transient inhibition of mitochondrial function following methamphetamine or 3,4-methylenedioxymethamphetamine administration. Eur J Pharmacol 398:11–8

    CAS  PubMed  Google Scholar 

  • Cadet JL, Jayanthi S, Deng X (2005) Methamphetamine-induced neuronal apoptosis involves the activation of multiple death pathways. Review. Neurotox Res 8:199–206

    CAS  PubMed  Google Scholar 

  • Calabrese B, Halpain S (2005) Essential role for the PKC target MARCKS in maintaining dendritic spine morphology. Neuron 48:77–90

    CAS  PubMed  Google Scholar 

  • Cardoso CM, Almeida LM, Custódio JB (2002) 4-Hydroxytamoxifen is a potent inhibitor of the mitochondrial permeability transition. Mitochondrion 1:485–95

    CAS  PubMed  Google Scholar 

  • Cardoso CM, Almeida LM, Custódio JB (2004) Protection of tamoxifen against oxidation of mitochondrial thiols and NAD(P)H underlying the permeability transition induced by prooxidants. Chem Biol Interact 148:149–61

    CAS  PubMed  Google Scholar 

  • Casabona G (1997) Intracellular signal modulation: a pivotal role for protein kinase C. Prog Neuro-Psychopharmacol Biol Psychiatry 21:407–25

    CAS  Google Scholar 

  • Cechinel-Recco K, Valvassori SS, Varela RB, Resende WR, Arent CO, Vitto MF, Luz G, de Souza CT, Quevedo J (2012) Lithium and tamoxifen modulate cellular plasticity cascades in animal model of mania. J Psychopharmacol 26:1594–604

    PubMed  Google Scholar 

  • Cervo L, Mukherjee S, Bertaglia A, Samanin R (1997) Protein kinases A and C are involved in the mechanisms underlying consolidation of cocaine place conditioning. Brain Res 775:30–6

    CAS  PubMed  Google Scholar 

  • Chen G, Manji HK, Hawver DB, Wright CB, Potter WZ (1994) Chronic sodium valproate selectively decreases protein kinase C alpha and epsilon in vitro. J Neurochem 63:2361–4

    CAS  PubMed  Google Scholar 

  • Chen L, Hahn H, Wu G, Chen CH, Liron T, Schechtman D, Cavallaro G, Banci L, Guo Y, Bolli R, Dorn GW, Mochly-Rosen D (2001) Opposing cardioprotective actions and parallel hypertrophic effects of delta PKC and epsilon PKC. Proc Natl Acad Sci U S A 98:11114–9

    CAS  PubMed Central  PubMed  Google Scholar 

  • Churchill E, Budas G, Vallentin A, Koyanagi T, Mochly-Rosen D (2008) PKC isozymes in chronic cardiac disease: possible therapeutic targets? Annu Rev Pharmacol Toxicol 48:569–99

    CAS  PubMed  Google Scholar 

  • Colombo C, Benedetti F, Barbini B, Campori E, Smeraldi E (1999) Rate of switch from depression into mania after therapeutic sleep deprivation in bipolar depression. Psychiatry Res 86:267–70

    CAS  PubMed  Google Scholar 

  • Couldwell WT, Hinton DR, Surnock AA, DeGiorgio CM, Weiner LP, Apuzzo ML, Masri L, Law RE, Weiss MH (1996) Treatment of recurrent malignant gliomas with chronic oral high-dose tamoxifen. Clin Cancer Res 2:619–22

    CAS  PubMed  Google Scholar 

  • Craske ML, Fivaz M, Batada NN, Meyer T (2005) Spines and neurite branches function as geometric attractors that enhance protein kinase C action. J Cell Biol 170:1147–58

    CAS  PubMed  Google Scholar 

  • Das Evcimen N, King GL (2007) The role of protein kinase C activation and the vascular complications of diabetes. Pharmacol Res 55:498–510

    CAS  PubMed  Google Scholar 

  • Dempsey EC, Cool CD, Littler CM (2007) Lung disease and PKCs. Pharmacol Res 55:545–59

    CAS  PubMed  Google Scholar 

  • Dencker D, Husum H (2010) Antimanic efficacy of retigabine in a proposed mouse model of bipolar disorder. Behav Brain Res 207:78–83

    CAS  PubMed  Google Scholar 

  • Deng Y, Kohlwein SD, Mannella CA (2002) Fasting induces cyanide-resistant respiration and oxidative stress in the amoeba Chaos carolinensis: implications for the cubic structural transition in mitochondrial membranes. Protoplasma 219:160–7

    CAS  PubMed  Google Scholar 

  • DiazGranados N, Zarate CA Jr (2008) A review of the preclinical and clinical evidence for protein kinase C as a target for drug development for bipolar disorder. Curr Psychiatry Rep 10:510–9

    PubMed Central  PubMed  Google Scholar 

  • Einat H (2006) Modelling facets of mania—new directions related to the notion of endophenotypes. J Psychopharmacol 20:714–22

    PubMed  Google Scholar 

  • Einat H (2007a) Different behaviors and different strains: potential new ways to model bipolar disorder. Neurosci Biobehav Rev 31:850–7

    PubMed  Google Scholar 

  • Einat H (2007b) Establishment of a battery of simple models for facets of bipolar disorder: a practical approach to achieve increased validity, better screening and possible insights into endophenotypes of disease. Behav Genet 37:244–55

    PubMed  Google Scholar 

  • Einat H, Chen G, Manji H (2004) Possible involvement of protein kinase C in the pathophysiology and treatment of bipolar disorder. Harefuah 143(420–5):462

    Google Scholar 

  • Einat H, Yuan P, Szabo ST, Dogra S, Manji HK (2007) Protein kinase C inhibition by tamoxifen antagonizes manic-like behavior in rats: implications for the development of novel therapeutics for bipolar disorder. Neuropsychobiology 55:123–31

    CAS  PubMed  Google Scholar 

  • Ferreira JC, Koyanagi T, Palaniyandi SS, Fajardo G, Churchill EN, Budas G, Disatnik MH, Bernstein D, Brum PC, Mochly-Rosen D (2011) Pharmacological inhibition of βIIPKC is cardioprotective in late-stage hypertrophy. J Mol Cell Cardiol 51:980–7

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fibiger HC (1995) Neurobiology of depression: focus on dopamine. In: Gessa GL, Fratta W, Pani L, Serra G (eds) Depression and mania: from neurobiology to treatment. Raven, New York, pp 1–18

    Google Scholar 

  • Flaisher-Grinberg S, Overgaard S, Einat H (2009) Attenuation of high sweet solution preference by mood stabilizers: a possible mouse model for the increased reward-seeking domain of mania. J Neurosci Methods 177:44–50

    CAS  PubMed  Google Scholar 

  • Frey BN, Valvassori SS, Reus GZ, Martins MR, Petronilho FC, Bardini K, Dal-Pizzol F, Kapczinski F, Quevedo J (2006) Effects of lithium and valproate on amphetamine-induced oxidative stress generation in an animal model of mania. J Psychiatry Neurosci 31:326–32

    PubMed Central  PubMed  Google Scholar 

  • Friedman E, Hoau Yan W, Levinson D, Connell TA, Singh H (1993) Altered platelet protein kinase C activity in bipolar affective disorder, manic episode. Biol Psychiatry 33:520–5

    CAS  PubMed  Google Scholar 

  • Garrido JL, Godoy JA, Alvarez A, Bronfman M, Inestrosa NC (2002) Protein kinase C inhibits amyloid beta peptide neurotoxicity by acting on members of the Wnt pathway. FASEB J 16:1982–4

    CAS  PubMed  Google Scholar 

  • Geraldes P, King GL (2010) Activation of protein kinase C isoforms and its impact on diabetic complications. Circ Res 106:1319–31

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gessa GL, Pani L, Fadda P, Fratta W (1995) Sleep deprivation in the rat: an animal model of mania. Eur Neuropsychopharmacol 5(Suppl):89–93

    CAS  PubMed  Google Scholar 

  • Geyer MA (2008) Developing translational animal models for symptoms of schizophrenia or bipolar mania. Neurotox Res 14:71–8

    CAS  PubMed Central  PubMed  Google Scholar 

  • Giambalvo CT (1992a) Protein kinase C and dopamine transport—1. Effects of amphetamine in vivo. Neuropharmacology 31:1201–10

    CAS  PubMed  Google Scholar 

  • Giambalvo CT (1992b) Protein kinase C and dopamine transport—2. Effects of amphetamine in vitro. Neuropharmacology 31:1211–22

    CAS  PubMed  Google Scholar 

  • Gitlin M (2006) Treatment-resistant bipolar disorder. Mol Psychiatry 11:227–40

    CAS  PubMed  Google Scholar 

  • Gnegy ME, Hong P, Ferrell ST (1993) Phosphorylation of neuromodulin in rat striatum after acute and repeated, intermittent amphetamine. Brain Res Mol Brain Res 20:289–98

    CAS  PubMed  Google Scholar 

  • Goodwin FK, Jamison KR (2007) Manic-depressive illness: bipolar disorders and recurrent depression, 2nd edn. Oxford University Press, London

    Google Scholar 

  • Gould TD, Einat H (2007) Animal models of bipolar disorder and mood stabilizer efficacy: a critical need for improvement. Neurosci Biobehav Rev 31:825–31

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hahn CG, Friedman E (1999) Abnormalities in protein kinase C signaling and the pathophysiology of bipolar disorder. Bipolar Disord 1:81–6

    CAS  PubMed  Google Scholar 

  • Huang KP (1990) Role of protein kinase C in cellular regulation. Biofactors 2:171–8

    CAS  PubMed  Google Scholar 

  • Inagaki K, Churchill E, Mochly-Rosen D (2006) Epsilon protein kinase C as a potential therapeutic target for the ischemic heart. Cardiovasc Res 70:222–30

    CAS  PubMed  Google Scholar 

  • Jordan VC (1992) The role of tamoxifen in the treatment and prevention of breast cancer. Curr Probl Cancer 16:129–76

    CAS  PubMed  Google Scholar 

  • Jordan VC (2003) Tamoxifen: a most unlikely pioneering medicine. Nat Rev Drug Discov 2:205–13

    CAS  PubMed  Google Scholar 

  • Kantor L, Gnegy ME (1998) Protein kinase C inhibitors block amphetamine-mediated dopamine release in rat striatal slices. J Pharmacol Exp Ther 284:592–8

    CAS  PubMed  Google Scholar 

  • Kara NZ, Einat H (2013) Rodent models for mania: practical approaches. Cell Tissue Res 354:191–201

    CAS  PubMed  Google Scholar 

  • Karn A, Jha AK, Shrestha S, Acharya B, Poudel S, Bhandari RB (2010) Tamoxifen for breast cancer. JNMA J Nepal Med Assoc 49:62–7

    CAS  PubMed  Google Scholar 

  • Kato T (2008) Molecular neurobiology of bipolar disorder: a disease of 'mood-stabilizing neurons'?. Trends Neurosci 31:495–503

    Google Scholar 

  • Kimelberg HK, Feustel PJ, Jin Y, Paquette J, Boulos A, Keller RW, Tranmer BI (2000) Acute treatment with tamoxifen reduces ischemic damage following middle cerebral artery occlusion. Neuroreport 11:2675–9

    CAS  PubMed  Google Scholar 

  • Krishnan KR (2005) Psychiatric and medical comorbidities of bipolar disorder. Psychosom Med 67:1–8

    PubMed  Google Scholar 

  • Kulkarni J, Garland KA, Scaffidi A, Headey B, Anderson R, de Castella A, Fitzgerald P, Davis SR (2006) A pilot study of hormone modulation as a new treatment for mania in women with bipolar affective disorder. Psychoneuroendocrinology 31:543–7

    CAS  PubMed  Google Scholar 

  • Kuloglu M, Ustundag B, Atmaca M, Canatan H, Tezcan AE, Cinkilinc N (2002) Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder. Cell Biochem Funct 20:171–5

    CAS  PubMed  Google Scholar 

  • Kupfer DJ (2005) The increasing medical burden in bipolar disorder. Jama 293:2528–30

    CAS  PubMed  Google Scholar 

  • Kurita M, Nishino S, Ohtomo K, Rai M, Shirakawa H, Mashiko H, Niwa S, Nakahata N (2007) Sodium valproate at therapeutic concentrations changes Ca2+ response accompanied with its weak inhibition of protein kinase C in human astrocytoma cells. Prog Neuropsychopharmacol Biol Psychiatry 31:600–4

    Google Scholar 

  • Kuruvilla A, Uretsky NJ (1981) Effect of sodium valproate on motor function regulated by the activation of GABA receptors. Psychopharmacol (Berl) 72:167–72

    CAS  Google Scholar 

  • Lenox RH, Watson DG, Patel J, Ellis J (1992) Chronic lithium administration alters a prominent PKC substrate in rat hippocampus. Brain Res 570:333–40

    CAS  PubMed  Google Scholar 

  • Lerer B, Globus M, Brik E, Hamburger R, Belmaker RH (1984) Effect of treatment and withdrawal from chronic lithium in rats on stimulant-induced responses. Neuropsychobiology 11:28–32

    CAS  PubMed  Google Scholar 

  • MacDonald JF, Kotecha SA, Lu WY, Jackson MF (2001) Convergence of PKC-dependent kinase signal cascades on NMDA receptors. Curr Drug Targets 2:299–312

    CAS  PubMed  Google Scholar 

  • Machado-Vieira R, Kapczinski F, Soares JC (2004) Perspectives for the development of animal models of bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry 28:209–24

    PubMed  Google Scholar 

  • Machado-Vieira R, Salvadore G, DiazGranados N, Ibrahim L, Latov D, Wheeler-Castillo C, Baumann J, Henter ID, Zarate CA (2010) New therapeutic targets for mood disorders. Sci World J 10:713–26

    CAS  Google Scholar 

  • Mackay HJ, Twelves CJ (2007) Targeting the protein kinase C family: are we there yet? Nat Rev Cancer 7:554–62

    CAS  PubMed  Google Scholar 

  • Maioli E, Valacchi G (2010) Rottlerin: bases for a possible usage in psoriasis. Curr Drug Metab 11:425–30

    CAS  PubMed  Google Scholar 

  • Malkesman O, Austin DR, Chen G, Manji HK (2009) Reverse translational strategies for developing animal models of bipolar disorder. Dis Model Mech 2:238–45

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mamelak M (1978) An amphetamine model of manic depressive illness. Int Pharmacopsychiatry 13:193–208

    CAS  PubMed  Google Scholar 

  • Manji HK, Bersudsky Y, Chen G, Belmaker RH, Potter WZ (1996) Modulation of protein kinase C isozymes and substrates by lithium: the role of myo-inositol. Neuropsychopharmacol 15:370–81

    Google Scholar 

  • Manji H (2008) The role of synaptic and cellular plasticity cascades in the pathophysiology and treatment of bipolar disorder. Actas Esp Psiquiatr 36(Suppl 1):1–2

    Google Scholar 

  • Manji HK, Lenox RH (2000) Signaling: cellular insights into the pathophysiology of bipolar disorder. Biol Psychiatry 48:518–30

    CAS  PubMed  Google Scholar 

  • Manji HK, Etcheberrigaray R, Chen G, Olds JL (1993) Lithium decreases membrane-associated protein kinase C in hippocampus: selectivity for the alpha isozyme. J Neurochem 61:2303–10

    CAS  PubMed  Google Scholar 

  • Mastronardi L, Puzzilli F, Couldwell WT, Farah JO, Lunardi P (1998) Tamoxifen and carboplatin combinational treatment of high-grade gliomas. Results of a clinical trial on newly diagnosed patients. J Neurooncol 38:59–68

    CAS  PubMed  Google Scholar 

  • Meinhard N, Kessing LV, Vinberg M (2013) The role of estrogen in bipolar disorder, a review. Nord J Psychiatry.

  • Mellor H, Parker PJ (1998) The extended protein kinase C superfamily. Biochem J 332(Pt 2):281–92

    CAS  PubMed  Google Scholar 

  • Mochly-Rosen D, Das K, Grimes KV (2012) Protein kinase C, an elusive therapeutic target? Nat Rev Drug Discov 11:937–57

    CAS  PubMed Central  PubMed  Google Scholar 

  • Moretti M, Valvassori SS, Steckert AV, Rochi N, Benedet J, Scaini G, Kapczinski F, Streck EL, Zugno AI, Quevedo J (2011) Tamoxifen effects on respiratory chain complexes and creatine kinase activities in an animal model of mania. Pharmacol Biochem Behav 98:304–10

    CAS  PubMed  Google Scholar 

  • Morgan MA, Pfaff DW (2001) Effects of estrogen on activity and fear-related behaviors in mice. Horm Behav 40:472–82

    CAS  PubMed  Google Scholar 

  • Morgan MA, Pfaff DW (2002) Estrogen's effects on activity, anxiety, and fear in two mouse strains. Behav Brain Res 132:85–93

    CAS  PubMed  Google Scholar 

  • Morgan MA, Schulkin J, Pfaff DW (2004) Estrogens and non-reproductive behaviors related to activity and fear. Neurosci Biobehav Rev 28:55–63

    CAS  PubMed  Google Scholar 

  • Murriel CL, Mochly-Rosen D (2003) Opposing roles of delta and epsilonPKC in cardiac ischemia and reperfusion: targeting the apoptotic machinery. Arch Biochem Biophys 420:246–54

    CAS  PubMed  Google Scholar 

  • Nestler EJ, Hyman SE (2010) Animal models of neuropsychiatric disorders. Nat Neurosci 13:1161–9

    CAS  PubMed Central  PubMed  Google Scholar 

  • Newton AC (1995) Protein kinase C. Seeing two domains. Curr Biol 5:973–6

    CAS  PubMed  Google Scholar 

  • Nierenberg AA (2010) A critical appraisal of treatments for bipolar disorder. Prim Care Companion J Clin Psychiatry 12:23–9

    PubMed Central  PubMed  Google Scholar 

  • Nishizuka Y (1992) Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258:607–14

    CAS  PubMed  Google Scholar 

  • Nishizuka Y, Nakamura S (1995) Lipid mediators and protein kinase C for intracellular signalling. Clin Exp Pharmacol Physiol Suppl 22:S202–3

    CAS  PubMed  Google Scholar 

  • Nogues X (1997) Protein kinase C, learning and memory: a circular determinism between physiology and behaviour. Progress Neuro-psychopharmacol Biol Psychiatry 21:507–29

    CAS  Google Scholar 

  • Obata T (2006) Tamoxifen protect against hydroxyl radical generation induced by phenelzine in rat striatum. Toxicology 222:46–52

    CAS  PubMed  Google Scholar 

  • Ohno S, Kawasaki H, Imajoh S, Suzuki K, Inagaki M, Yokokura H, Sakoh T, Hidaka H (1987) Tissue-specific expression of three distinct types of rabbit protein kinase C. Nature 325:161–6

    CAS  PubMed  Google Scholar 

  • Ozcan ME, Gulec M, Ozerol E, Polat R, Akyol O (2004) Antioxidant enzyme activities and oxidative stress in affective disorders. Int Clin Psychopharmacol 19:89–95

    PubMed  Google Scholar 

  • Pandey GN, Ren X, Dwivedi Y, Pavuluri MN (2008) Decreased protein kinase C (PKC) in platelets of pediatric bipolar patients: effect of treatment with mood stabilizing drugs. J Psychiatr Res 42:106–16

    PubMed Central  PubMed  Google Scholar 

  • Peet M, Peters S (1995) Drug-induced mania. Drug Saf 12:146–53

    CAS  PubMed  Google Scholar 

  • Pereira M, Martynhak BJ, Baretta IP, Correia D, Siba IP, Andreatini R (2011) Antimanic-like effect of tamoxifen is not reproduced by acute or chronic administration of medroxyprogesterone or clomiphene. Neurosci Lett 500:95–8

    CAS  PubMed  Google Scholar 

  • Perry W, Minassian A, Paulus MP, Young JW, Kincaid MJ, Ferguson EJ, Henry BL, Zhuang X, Masten VL, Sharp RF, Geyer MA (2009) A reverse-translational study of dysfunctional exploration in psychiatric disorders: from mice to men. Arch Gen Psychiatry 66:1072–80

    PubMed Central  PubMed  Google Scholar 

  • Perry W, Minassian A, Henry B, Kincaid M, Young JW, Geyer MA (2010) Quantifying over-activity in bipolar and schizophrenia patients in a human open field paradigm. Psychiatry Res 178:84–91

    PubMed Central  PubMed  Google Scholar 

  • Pollack IF, DaRosso RC, Robertson PL, Jakacki RL, Mirro JR Jr, Blatt J, Nicholson S, Packer RJ, Allen JC, Cisneros A, Jordan VC (1997) A phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood. Clin Cancer Res 3:1109–15

    CAS  PubMed  Google Scholar 

  • Post RM, Weiss SR (1989) Sensitization, kindling, and anticonvulsants in mania. J Clin Psychiatry 50(Suppl):23–30, discussion 45–7

    PubMed  Google Scholar 

  • Rajkowska G (2002) Cell pathology in bipolar disorder. Bipolar Disord 4:105–16

    PubMed  Google Scholar 

  • Ramakers GM, Pasinelli P, Hens JJ, Gispen WH, De Graan PN (1997) Protein kinase C in synaptic plasticity: changes in the in situ phosphorylation state of identified pre- and postsynaptic substrates. Prog Neuropsychopharmacol Biol Psychiatry 21:455–86

    CAS  PubMed  Google Scholar 

  • Ranjekar PK, Hinge A, Hegde MV, Ghate M, Kale A, Sitasawad S, Wagh UV, Debsikdar VB, Mahadik SP (2003) Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res 121:109–22

    CAS  PubMed  Google Scholar 

  • Sabioni P, Baretta IP, Ninomiya EM, Gustafson L, Rodrigues AL, Andreatini R (2008) The antimanic-like effect of tamoxifen: behavioural comparison with other PKC-inhibiting and antiestrogenic drugs. Prog Neuropsychopharmacol Biol Psychiatry 32:1927–31

    CAS  PubMed  Google Scholar 

  • Schloesser RJ, Huang J, Klein PS, Manji HK (2007) Cellular Plasticity Cascades in the Pathophysiology and Treatment of Bipolar Disorder. Neuropsychopharmacology 33:110–133

    PubMed  Google Scholar 

  • Shaldubina A, Einat H, Szechtman H, Shimon H, Belmaker RH (2002) Preliminary evaluation of oral anticonvulsant treatment in the quinpirole model of bipolar disorder. J Neural Transm 109:433–40

    CAS  PubMed  Google Scholar 

  • Smith DF (1981) Central and peripheral effects of lithium on amphetamine-induced hyperactivity in rats. Pharmacol Biochem Behav 14:439–42

    CAS  PubMed  Google Scholar 

  • Smith LA, Cornelius V, Warnock A, Tacchi MJ, Taylor D (2007) Pharmacological interventions for acute bipolar mania: a systematic review of randomized placebo-controlled trials. Bipolar Disord 9:551–60

    CAS  PubMed  Google Scholar 

  • Soares JC, Chen G, Dippold CS, Wells KF, Frank E, Kupfer DJ, Manji HK, Mallinger AG (2000) Concurrent measures of protein kinase C and phosphoinositides in lithium-treated bipolar patients and healthy individuals: a preliminary study. Psychiatry Res 95:109–18

    Google Scholar 

  • Stabel S, Parker PJ (1991) Protein kinase C. Pharmacol Ther 51:71–95

    CAS  PubMed  Google Scholar 

  • Steckert AV, Valvassori SS, Mina F, Lopes-Borges J, Varela RB, Kapczinski F, Dal-Pizzol F, Quevedo J (2012) Protein kinase C and oxidative stress in an animal model of mania. Curr Neurovasc Res 9:47–57

    CAS  PubMed  Google Scholar 

  • Steketee JD (1993) Injection of the protein kinase inhibitor H7 into the A10 dopamine region blocks the acute responses to cocaine: behavioral and in vivo microdialysis studies. Neuropharmacology 32:1289–97

    CAS  PubMed  Google Scholar 

  • Steketee JD (1994) Intra-A10 injection of H7 blocks the development of sensitization to cocaine. Neuroreport 6:69–72

    CAS  PubMed  Google Scholar 

  • Steketee JD (1997) Intra-ventral tegmental area administration of H7 delays, but does not prevent the development of cocaine-induced sensitization. Brain Res Bull 43:565–71

    CAS  PubMed  Google Scholar 

  • Szabo ST, Machado-Vieira R, Yuan P, Wang Y, Wei Y, Falke C, Cirelli C, Tononi G, Manji HK, Du J (2009) Glutamate receptors as targets of protein kinase C in the pathophysiology and treatment of animal models of mania. Neuropharmacology 56:47–55

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tanaka C, Nishizuka Y (1994) The protein kinase C family for neuronal signaling. Ann Rev Neurosci 17:551–67

    CAS  PubMed  Google Scholar 

  • Tang P, Roldan G, Brasher PM, Fulton D, Roa W, Murtha A, Cairncross JG, Forsyth PA (2006) A phase II study of carboplatin and chronic high-dose tamoxifen in patients with recurrent malignant glioma. J Neurooncol 78:311–6

    CAS  PubMed  Google Scholar 

  • Torres IJ, DeFreitas VG, DeFreitas CM, Kauer-Sant'Anna M, Bond DJ, Honer WG, Lam RW, Yatham LN (2010) Neurocognitive functioning in patients with bipolar I disorder recently recovered from a first manic episode. J Clin Psychiatry 71:1234–42

    PubMed  Google Scholar 

  • Totoń E, Ignatowicz E, Skrzeczkowska K, Rybczyńska M (2011) Protein kinase Cε as a cancer marker and target for anticancer therapy. Pharmacol Rep 63:19–29

    PubMed  Google Scholar 

  • Tuquet C, Dupont J, Mesneau A, Roussaux J (2000) Effects of tamoxifen on the electron transport chain of isolated rat liver mitochondria. Cell Biol Toxicol 16:207–19

    CAS  PubMed  Google Scholar 

  • Wade GN (1972) Gonadal hormones and behavioral regulation of body weight. Physiol Behav 8:523–34

    CAS  PubMed  Google Scholar 

  • Walf AA, Frye CA (2006) A review and update of mechanisms of estrogen in the hippocampus and amygdala for anxiety and depression behavior. Neuropsychopharmacology 31:1097–111

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang HY, Friedman E (1989) Lithium inhibition of protein kinase C activation-induced serotonin release. Psychopharmacol (Berl) 99:213–8

    CAS  Google Scholar 

  • Wang HY, Friedman E (1996) Enhanced protein kinase C activity and translocation in bipolar affective disorder brains. Biol Psychiatry 40:568–75

    CAS  PubMed  Google Scholar 

  • Wang HY, Markowitz P, Levinson D, Undie AS, Friedman E (1999) Increased membrane-associated protein kinase C activity and translocation in blood platelets from bipolar affective disorder patients. J Psychiatr Res 33:171–9

    Google Scholar 

  • Wang H, Friedman E (2001) Increased association of brain protein kinase C with the receptor for activated C kinase-1 (RACK1) in bipolar affective disorder. Biol Psychiatry 50:364–70

    CAS  PubMed  Google Scholar 

  • Watson DG, Lenox RH (1996) Chronic lithium-induced down-regulation of MARCKS in immortalized hippocampal cells: potentiation by muscarinic receptor activation. J Neurochem 67:767–77

    CAS  PubMed  Google Scholar 

  • Wehr TA (1991) Sleep-loss as a possible mediator of diverse causes of mania. Br J Psychiatry 159:576–8

    CAS  PubMed  Google Scholar 

  • Wehr TA, Goodwin FK, Wirz-Justice A, Breitmaier J, Craig C (1982) 48-hour sleep-wake cycles in manic-depressive illness: naturalistic observations and sleep deprivation experiments. Arch Gen Psychiatry 39:559–65

    CAS  PubMed  Google Scholar 

  • Wehr TA, Sack DA, Rosenthal NE (1987) Sleep reduction as a final common pathway in the genesis of mania. Am J Psychiatry 144:201–4

    CAS  PubMed  Google Scholar 

  • Wu-Zhang AX, Newton AC (2013) Protein kinase C pharmacology: refining the toolbox. Biochem J 452:195–209

    CAS  PubMed  Google Scholar 

  • Yildiz A, Guleryuz S, Ankerst DP, Ongur D, Renshaw PF (2008) Protein kinase C inhibition in the treatment of mania: a double-blind, placebo-controlled trial of tamoxifen. Arch Gen Psychiatry 65:255–63

    CAS  PubMed  Google Scholar 

  • Young JW, Henry BL, Geyer MA (2011) Predictive animal models of mania: hits, misses and future directions. Br J Pharmacol 164:1263–84

    CAS  PubMed  Google Scholar 

  • Zanin-Zhorov A, Dustin ML, Blazar BR (2011) PKC-θ function at the immunological synapse: prospects for therapeutic targeting. Trends Immunol 32:358–63

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zarate CA, Manji HK (2009) Protein kinase C inhibitors: rationale for use and potential in the treatment of bipolar disorder. CNS Drugs 23:569–82

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zarate CA Jr, Singh JB, Carlson PJ, Quiroz J, Jolkovsky L, Luckenbaugh DA, Manji HK (2007) Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot study. Bipolar Disord 9:561–70

    CAS  PubMed  Google Scholar 

  • Zhang D, Anantharam V, Kanthasamy A, Kanthasamy AG (2007) Neuroprotective effect of protein kinase C delta inhibitor rottlerin in cell culture and animal models of Parkinson's disease. J Pharmacol Exp Ther 322:913–22

    CAS  PubMed  Google Scholar 

  • Zhao Y, Wang LM, Chaiswing L, Yen HC, Oberley TD, Lien YC, Lin SM, Mattson MP, St Clair D (2006) Tamoxifen protects against acute tumor necrosis factor alpha-induced cardiac injury via improving mitochondrial functions. Free Radic Biol Med 40:1234–41

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to declare our deepest appreciation for the critical input and contributions of Prof. Roberto Frussa-Filho (in memoriam).

Conflict of interest

All researchers listed in the present study reported no biomedical financial interests or potential conflicts of interest.

Author information

Authors and Affiliations

  1. Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil

    Fernanda Armani, Monica Levy Andersen & José Carlos Fernandes Galduróz

  2. Rua Botucatu, 862, 04023-062, São Paulo, SP, Brazil

    José Carlos Fernandes Galduróz

Authors
  1. Fernanda Armani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Monica Levy Andersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. José Carlos Fernandes Galduróz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to José Carlos Fernandes Galduróz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Armani, F., Andersen, M.L. & Galduróz, J.C.F. Tamoxifen use for the management of mania: a review of current preclinical evidence. Psychopharmacology 231, 639–649 (2014). https://doi.org/10.1007/s00213-013-3397-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-013-3397-x

Keywords

Search

Navigation