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Activity of mitochondrial respiratory chain is increased by chronic administration of antidepressants

Published online by Cambridge University Press:  24 June 2014

Giselli Scaini ,
Débora D. Maggi ,
Bruna T. De-Nês ,
Cinara L. Gonçalves ,
Gabriela K. Ferreira ,
Brena P. Teodorak ,
Gisele D. Bez ,
Gustavo C. Ferreira ,
Patricia F. Schuck  and
João Quevedo
...Show all authors
Giselli Scaini
Affiliation:
Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina
Débora D. Maggi
Affiliation:
Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina
Bruna T. De-Nês
Affiliation:
Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina
Cinara L. Gonçalves
Affiliation:
Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina
Gabriela K. Ferreira
Affiliation:
Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina
Brena P. Teodorak
Affiliation:
Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina
Gisele D. Bez
Affiliation:
Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina
Gustavo C. Ferreira
Affiliation:
Programa de Pós-graduação em Ciências da Saúde, Universidade do Sul de Santa Catarina, Tubarão, SC, Brazil
Patricia F. Schuck
Affiliation:
Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
João Quevedo
Affiliation:
Instituto Nacional de Ciência e Tecnologia Translacional em Medicina Laboratório de Neurociências, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
Emilio L. Streck*
Affiliation:
Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina
*
Emilio L. Streck, Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil. Tel: +55 48 3431 2539; Fax: +55 48 3431 2671; E-mail: emiliostreck@gmail.com
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Extract

Objective: Depressive disorders, including major depression, are serious and disabling for affected patients. Although the neurobiological understanding of major depressive disorder focuses mainly on the monoamine hypothesis, the exact pathophysiology of depression is not fully understood.

Methods: Animals received daily intra-peritoneal injections of paroxetine (10 mg/kg), nortriptyline (15 mg/kg) or venlafaxine (10 mg/kg) in 1.0 ml/kg volume for 15 days. Twelve hours after the last injection, the rats were killed by decapitation, where the brain was removed and homogenised. The activities of mitochondrial respiratory chain complexes in different brain structures were measured.

Results: We first verified that chronic administration of paroxetine increased complex I activity in prefrontal cortex, hippocampus, striatum and cerebral cortex. In addition, complex II activity was increased by the same drug in hippocampus, striatum and cerebral cortex and complex IV activity in prefrontal cortex. Furthermore, chronic administration of nortriptyline increased complex II activity in hippocampus and striatum and complex IV activity in prefrontal cortex, striatum and cerebral cortex. Finally, chronic administration of venlafaxine increased complex II activity in hippocampus, striatum and cerebral cortex and complex IV activity in prefrontal cortex.

Conclusion: On the basis of the present findings, it is tempting to speculate that an increase in brain energy metabolism by the antidepressant paroxetine, nortriptyline and venlafaxine could play a role in the mechanism of action of these drugs. These data corroborate with other studies suggesting that some antidepressants modulate brain energy metabolism.

Keywords

brainmitochondrial respiratory chainnortriptylineparoxetinevenlafaxine
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 23 , Issue 3 , June 2011 , pp. 112 - 118
Copyright
Copyright © Cambridge University Press 2011

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References

1.Kessler, RC, Walters, EE.Epidemiology of DSM-III-R major depression and minor depression among adolescents and young adults in the National Comorbidity Survey. Depress Anxiety 1998;7:3–14.Google Scholar
2.Turner, JR, Gil, AG.Psychiatric and substance use disorders in South Florida racial/ethnic and gender contrasts in a young adult cohort. Arch Gen Psychiatry 2002;59:43–50.Google Scholar
3.Kessler, RC, Berglund, P, Demler, O, Jin, R, Merikans, KR, Walters, EE.Lifetime prevalence and age-of-onset distributions of DSM-IV disorder in the national comorbidity survey replication. Arch Gen Psychiatry 2005;62: 593–768.Google Scholar
4.Murphy, JM, Laird, NM, Monson, RR, Sobol, AM, Leighton, AH.40-year perspective on the prevalence of depression. The Stirling County Study. Arch Gen Psychiatry 2000;57:209–215.CrossRefGoogle ScholarPubMed
5World Health Organization (WHO). 2009. Programmes and projects/mental health/disorders management/depression. URL http://www.who.int/mental_health/management/depression/definition/en/ [accessed on 1 March 2010].Google Scholar
6.Skolnick, P.Beyond monoamine-based therapies: clues to new approaches. J Clin Psychiatry 2002;63:19–23.Google ScholarPubMed
7.Charney, DS.Monoamine dysfunction and the pathophysiology and treatment of depression. J Clin Psychiatry 1998;59:11–14.Google Scholar
8.Castrén, E.Is mood chemistry? Nat Rev Neurosci 2005;6:241–246.CrossRefGoogle ScholarPubMed
9.Shelton, RC.The molecular neurobiology of depression. Psychiatr Clin N Am 2007;30:1–11.Google Scholar
10.Krishnan, V, Nestler, EJ.The molecular neurobiology of depression. Nature 2008;894–902.Google Scholar
11.Zarate, CA Jr, Singh, JB, Carlson, PJ et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006;63:856–64.Google Scholar
12.Millan, MJ.Multi-target strategies for the improved treatment of depressive states: conceptual foundations and neuronal substrates, drug discovery and therapeutic application. Pharmacol Ther 2006;110:135–370.Google Scholar
13.Baghai, TC, Grunze, H, Sartorius, N.Antidepressant medications and other treatments of depressive disorders: a CINP task force report based on a review of evidence. Int J Neuropsychopharmacol 2007;10:S1–S207.Google Scholar
14.Morilak, DA, Frazer, A.Antidepressants and brain monoaminergic systems: a dimensional approach to understanding their behavioural effects in depression and anxiety disorders. Int J Neuropsychopharmacol 2007;7:193–218.CrossRefGoogle Scholar
15.Johnson, AM.Paroxetine: A pharmacological review. Int Clin Psychopharmacology 1992;6:15–24.Google Scholar
16.Richelson, E.Pharmacology of anti-depressants – characteristics of the ideal drug. Mayo Clin Proc 1999;69: 1069–1081.CrossRefGoogle Scholar
17.Duman, RS, Heninger, GR, Nestler, EJ.A molecular and cellular theory of depression. Arch Gen Psychiatry 1997;54:597–606.CrossRefGoogle ScholarPubMed
18.Calabrese, V, Scapagnini, G, Giuffrida-Stella, AM, Bates, TE, Clark, JB.Mitochondrial involvement in brain function and dysfunction: relevance to aging, neurodegenerative disorders and longevity. Neurochem Res 2001;26: 739–764.Google Scholar
19.Horn, D, Barrientos, A.Mitochondrial copper metabolism and delivery to cytochrome c oxidase. IUBMB Life 2008;60:421–429.Google Scholar
20.Blass, JP.Brain metabolism and brain disease: is metabolic deficiency the proximate cause of Alzheimer dementia? J Neurosci Res 2001;66:851–856.Google Scholar
21.Brennan, WA, Bird, ED, Aprille, JR.Regional mitochondrial respiratory activity in Huntington's disease brain. J Neurochem 1985;44:1948.CrossRefGoogle ScholarPubMed
22.Heales, SJ, Bolanõs, JP, Stewart, VC, Brookes, PS, Land, JM, Clark, JB.Nitric oxide, mitochondria and neurological disease. Biochim Biophys Acta 1999;1410:215–228.CrossRefGoogle ScholarPubMed
23.Schurr, A.Energy metabolism, stress hormones and neural recovery from cerebral ischemia/hypoxia. Neurochem Int 2002;41:1–8.Google Scholar
24.Monsalve, M, Borniquel, S, Valle, I, Lamas, S.Mitochondrial dysfunction in human pathologies. Front Biosci 2007;12:1131–1153.Google Scholar
25.Moreira, PI, Santos, MS, Oliveira, CR.Alzheimer's disease: a lesson from mitochondrial dysfunction. Antioxid Redox Signal 2007;9:1621–1630.Google Scholar
26.Moreira, PI, Santos, MS, Seiça, R, Oliveira, CR.Brain mitochondrial dysfunction as a link between Alzheimer's disease and diabetes. J Neurol Sci 2007;257:206–214.CrossRefGoogle Scholar
27.Tretter, L, Mayer-Takacs, D, Adam-Vizi, V.The effect of bovine serum albumin on the membrane potential and reactive oxygen species generation in succinate-supported isolated brain mitochondria. Neurochem Int 2007; 50:139–147.CrossRefGoogle ScholarPubMed
28.Petrosillo, G, Matera, M, Casanova, G, Ruggiero, FM, Paradies, G.Mitochondrial dysfunction in rat brain with aging: involvement of complex I, reactive oxygen species and cardiolipin. Neurochem Int 2008;53:126–131.Google Scholar
29.Kanarik, M, Matrov, D, Kõiv, K, Eller, M, Tõnissaar, M, Harro, J.Changes in regional long-term oxidative metabolism induced by partial serotonergic denervation and chronic variable stress in rat brain. Neurochem Int 2008;52: 432–437.Google Scholar
30.Stanyer, L, Jorgensen, W, Hori, O, Clark, JB, Heales, SJ.Inactivation of brain mitochondrial Lon protease by peroxynitrite precedes electron transport chain dysfunction. Neurochem Int 2008;53:95–101.Google Scholar
31.Nestler, EJ, McMahon, A, Sabban, EL, Tallman, JF, Duman, RS.Chronic antidepressant administration decreases the expression of tyrosine hydroxylase in the rat locus coeruleus. Proc Natl Acad Sci U S A 1990;87: 7522–7526.CrossRefGoogle ScholarPubMed
32.Berrocoso, E, Rojas-Corrales, MO, Micó, JA.Non- selective opioid receptor antagonism of the antidepressant-like effect of venlafaxine in the forced swimming test in mice. Neurosci Lett 2004;363:25–28.CrossRefGoogle ScholarPubMed
33.Casarotto, PC, Andreatini, R.Repeated paroxetine treatment reverses anhedonia induced in rats by chronic mild stress or dexamethasone. Eur Neuropsychopharmacol 2007;17:735–742.Google Scholar
34.Drapier, D, Bentué-Ferrer, D, Laviolle, B, Millet, B, Allain, H, Bourin, M, Reymann, JM.Effects of acute fluoxetine, paroxetine and desipramine on rats tested on the elevated plus-maze. Behav Brain Res 2007;176:202–209.Google Scholar
35.Ide, S, Fujiwara, S, Fujiwara, M et al. Antidepressant-like effect of venlafaxine is abolished in µ-opioid receptor-knockout mice. J Pharmacol Sci 2010;114:107–110.Google Scholar
36.Lowry, OH, Rosebough, NG, Farr, AL, Randall, RJ.Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–275.CrossRefGoogle ScholarPubMed
37.Cassina, A, Radi, R.Differential inhibitory Aation of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 1996;328:309–316.Google Scholar
38.Fischer, JC, Ruitenbeek, W, Berden, JA et al. Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 1985;153:23–26.CrossRefGoogle ScholarPubMed
39.Rustin, P, Chretien, D, Bourgeron, T et al. Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 1994;228:35–51.CrossRefGoogle ScholarPubMed
40.Rex, A, Schickert, R, Fink, H.Antidepressant-like effect of nicotinamide adenine dinucleotide in the forced swim test in rats. Pharmacol Biochem Behav 2004;77:303–307.CrossRefGoogle ScholarPubMed
41.Boekema, EJ, Braun, HP.Supramolecular structure of the mitochondrial oxidative phosphorylation system. J Chem Biol 2007;282:1–4.Google Scholar
42.Fattal, O, Budur, K, Vaughan, AJ, Franco, K.Review of the literature on major mental disorders in adult patients with mitochondrial diseases. Psychosomatics 2006; 47:1–7.CrossRefGoogle ScholarPubMed
43.Madrigal, JL, Olivenza, R, Moro, M et al. Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology 2001;24:420–429.Google Scholar
44.Gardner, A, Johansson, A, Wibom, R et al. Alterations of mitochondrial function and correlations with personality traits in selected major depressive disorder patients. J Affect Disord 2003;76:55–68.CrossRefGoogle ScholarPubMed
45.Gamaro, GD, Streck, EL, Matté, C, Prediger, ME, Wyse, AT, Dalmaz, C.Reduction of hippocampal Na+,K+-ATPase activity in rats subjected to an experimental model of depression. Neurochem Res 2003;28:1339–1344.CrossRefGoogle Scholar
46.Rezin, GT, Cardoso, MR, Gonçalves, CL et al. Inhibition of mitochondrial respiratory chain in brain of rats subjected to an experimental model of depression. Neurochem Int 2008;53:395–400.CrossRefGoogle Scholar
47.Assis, LC, Rezin, GT, Comim, CM et al. Effect of acute administration of ketamine and imipramine on creatine kinase activity in the brain of rats. Rev Bras Psiquiatr 2009;31:247–252.Google Scholar
48.Santos, PM, Scaini, G, Rezin, GT et al. Brain creatine kinase activity is increased by chronic administration of paroxetine. Brain Res Bull 2009;80:327–330.Google Scholar
49.Scaini, G, Santos, PM, Benedet, J et al. Evaluation of Krebs cycle enzymes in the brain of rats after chronic administration of paroxetine. Brain Res Bull 2010;82: 224–227.CrossRefGoogle Scholar
50.Consoni, FT, Vital, MA, Andreatini, R.Dual monoamine modulation for the antidepressant-like effect of lamotrigine in the modified forced swimming test. Eur Neuropsychopharmacol 2006;16:451–458.Google Scholar
51.Krass, M, Wegener, G, Vasar, E, Volke, V.The antidepressant action of imipramine and venlafaxine involves suppression of nitric oxide synthesis. Behav Brain Res 2011; 218:57–63.CrossRefGoogle ScholarPubMed
52.Streck, EL, Feier, G, Búrigo, M et al. Effects of electroconvulsive seizures on Na+, K+-ATPase activity in the rat hippocampus. Neurosci Lett 2006;404:254–257.Google Scholar
53.Búrigo, M, Roza, CA, Bassani, C et al. Decreased creatine kinase activity caused by electroconvulsive shock. Neurochem Res 2006;31:877–881.Google Scholar
54.Kálmán, J, Palotás, A, Juhász, A et al. Impact of venlafaxine on gene expression profile in lymphocytes of the elderly with major depression–evolution of antidepressants and the role of the “neuro-immune” system. Neurochem Res 2005;30:1429–1438.Google Scholar
55.Piubelli, C, Gruber, S, El Khoury, A, Mathé, AA, Domenici, E, Carboni, L.Nortriptyline influences protein pathways involved in carbohydrate metabolism and actin-related processes in a rat gene-environment model of depression. Eur Neuropsychopharmacol 2010. [E-pub ahead of print; DOI:10.1016/j.euroneuro.2010.11.003]Google Scholar
56.McHugh, PC, Rogers, GR, Loudon, B, Glubb, DM, Joyce, PR, Kennedy, MA. Proteomic analysis of embryonic stem cell-derived neural cells exposed to the antidepressant paroxetine. J Neurosci Res 2008;86:306–316.Google Scholar