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Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala

Published online by Cambridge University Press:  24 June 2014

Gislaine Z. Réus ,
Roberto B. Stringari ,
Karine F. Ribeiro ,
Tatiana Luft ,
Helena M. Abelaira ,
Gabriel R. Fries ,
Bianca W. Aguiar ,
Flávio Kapczinski ,
Jaime E. Hallak  and
Antônio W. Zuardi
...Show all authors
Gislaine Z. Réus
Affiliation:
Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
Roberto B. Stringari
Affiliation:
Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
Karine F. Ribeiro
Affiliation:
Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
Tatiana Luft
Affiliation:
Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
Helena M. Abelaira
Affiliation:
Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
Gabriel R. Fries
Affiliation:
Laboratório de Psiquiatria Molecular and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Bianca W. Aguiar
Affiliation:
Laboratório de Psiquiatria Molecular and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Flávio Kapczinski
Affiliation:
Laboratório de Psiquiatria Molecular and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Jaime E. Hallak
Affiliation:
Departamento de Neurociências e Ciências do Comportamento and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
Antônio W. Zuardi
Affiliation:
Departamento de Neurociências e Ciências do Comportamento and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
José A. Crippa
Affiliation:
Departamento de Neurociências e Ciências do Comportamento and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
João Quevedo*
Affiliation:
Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
*
Professor João Quevedo, MD, PhD, Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil. Tel: +554834312792; Fax: +554834312736; E-mail: quevedo@unesc.net
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Extract

Réus GZ, Stringari RB, Ribeiro KF, Luft T, Abelaira HM, Fries GR, Aguiar BW, Kapczinski F, Hallak JE, Zuardi AW, Crippa JA, Quevedo J. Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala.

Objective: Cannabidiol is a chemical constituent from Cannabis sativa and it has multiple mechanisms of action, including antidepressant effects. The main objective of the present study was to evaluate behavioural and molecular effects induced by administration of cannabidiol and imipramine in rats.

Methods: In the present study, rats were acutely or chronically treated for 14 days once a day with saline, cannabidiol (15, 30 and 60 mg/kg) or imipramine (30 mg/kg) and the animals behaviour was assessed in forced swimming and open-field tests. Afterwards, the prefrontal cortex, hippocampus and amygdala brain-derived neurotrophic factor (BDNF) levels were assessed by enzyme-linked immunosorbent sandwich assay.

Results: We observed that both acute and chronic treatments with imipramine at the dose of 30 mg/kg and cannabidiol at the dose of 30 mg/kg reduced immobility time and increased swimming time; climbing time was increased only with imipramine at the dose of 30 mg/kg, without affecting locomotor activity. In addition, chronic treatment with cannabidiol at the dose of 15 mg/kg and imipramine at the dose of 30 mg/kg increased BDNF levels in the rat amygdala.

Conclusion: In conclusion, our results indicate that cannabidiol has an antidepressant-like profile and could be a new pharmacological target for the treatment of major depression.

Keywords

brain-derived neurotrophic factorcannabidioldepressionforced swimming testimipramine
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 23 , Issue 5 , October 2011 , pp. 241 - 248
Copyright
Copyright © Cambridge University Press 2011

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References

1. Baune, BT, Adrian, I, Jacobi, F. Medical disorders affect health outcome and general functioning depending on comorbid major depression in the general population. J Psychosom Res 2007;62:109–118. CrossRefGoogle ScholarPubMed
2. Mathers, C, Loncar, D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006;3: 442. CrossRefGoogle ScholarPubMed
3. Castrén, E. Is mood chemistry? Nat Rev Neurosci 2005;6: 241–246. CrossRefGoogle ScholarPubMed
4. Duman, RS, Heninger, GR, Nestler, EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry 1997;54: 597–606. CrossRefGoogle ScholarPubMed
5. Moreira, FA, Guimarães, FS. Cannabidiol inhibits the hyperlocomotion induced by psychotomimetic drugs in mice. Eur J Pharmacol 2005;512:199–205. CrossRefGoogle ScholarPubMed
6. Souery, D, Amsterdam, J, de Montigny, C et al. Treatment resistant depression: methodological overview and operational criteria. Eur Neuropsychopharmacol 1999;9:83–91. CrossRefGoogle ScholarPubMed
7. Tomba, E, Grandi, S, Fava, GA. Therapeutic factors in depression: new strategies. Riv Psichiatr 2009;44:95–101. Google ScholarPubMed
8. Gaoni, Y, Mechoulam, RJ. The isolation and structure of delta-1-tetrahydrocannabinol and other neutral cannabinoids from hashish. Am Chem Soc 1971;93:217–224. CrossRefGoogle ScholarPubMed
9. Zuardi, AW, Shirakawa, I, Finkelfarb, E, Karniol, IG. Action of cannabidiol on the anxiety and other effects produced by Δ9-THC in normal subjects. Psychopharmacology 1982;76:245–250. CrossRefGoogle Scholar
10. Zuardi, AW, Crippa, JAS, Hallak, JEC, Moreira, FA, Guimarães, FS. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res 2006;39: 421–429. CrossRefGoogle ScholarPubMed
11. Pertwee, RG. Pharmacology of cannabinoids CB1 and CB2 receptors. Pharmacol Ther 1997;74:129–180. CrossRefGoogle ScholarPubMed
12. Herkenham, M, Lynn, AB, Johnson, MR, Melvin, LS, de Costa, BR, Rice, KC. Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 1991;11:563–583. CrossRefGoogle Scholar
13. Honório, KM, Arroio, A, Silva, . ABF – therapeutical aspects of compounds of the plant Cannabis sativa. Quím Nova 2006;29:318–325. CrossRefGoogle Scholar
14. Tsou, K, Brown, S, Sanudo-Pena, MC, Mackie, K, Walker, JM. Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 1998;83:393–411. CrossRefGoogle ScholarPubMed
15. Zuardi, AW. Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev Bras Psiquiatr 2008;30:271–280. CrossRefGoogle ScholarPubMed
16. Costa, B, Colleoni, M, Conti, S et al. Oral antiinflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. Naunyn Schmiedebergs Arch Pharmacol 2004;369:294–299. CrossRefGoogle ScholarPubMed
17. Sumariwalla, PF, Gallily, R, Tchilibon, S, Fride, E, Mechoulam, R, Feldmann, M. A novel synthetic, nonpsychoactive cannabinoid acid (HU-320) with anti-inflammatory properties in murine collagen-induced arthritis. Arthritis Rheum 2004;50:985–998. CrossRefGoogle ScholarPubMed
18. Walter, L, Franklin, A, Witting, A et al. Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J Neurosci 2003;23:1398–1405. CrossRefGoogle ScholarPubMed
19. Hampson, AJ, Grimaldi, M, Axelrod, J, Wink, D. Cannabidiol and delta-9 tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci U S A 1998;95: 8268–8273. CrossRefGoogle ScholarPubMed
20. Jacobsson, SO, RongÄrd, E, Stridh, M, Tiger, G, Fowler, SJ. Serum dependent effects of tamoxifen and cannabinoids upon C6 glioma cell viability. Biochem Pharmacol 2000; 60:1807–1813. CrossRefGoogle ScholarPubMed
21. Mechoulam, RE, Parker, LA, Gallily, R. Cannabidiol: an overview of some pharmacological aspects. J Clin Pharmacol 2002;42:11–19. CrossRefGoogle ScholarPubMed
22. Valvassori, SS, Elias, G, de Souza, B et al. Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of mania. J Psychopharmacol 2011;25:274–280.CrossRefGoogle Scholar
23. Dirikoc, S, Priola, SA, Marella, M, Zsurger, N, Chabry, J. Nonpsychoactive cannabidiol prevents prion accumulation and protects neurons against prion toxicity. J Neurosci 2007;27:9537–9544. CrossRefGoogle ScholarPubMed
24. El-Remessy, AB, Khalil, IE, Matragoon, S et al. Neuroprotective effect of delta-9-tetrahydrocannabinol and cannabidiol in N-Methyl-D-Aspartate-induced retinal neurotoxicity. Am J Pathol 2003;163:1997–2008. CrossRefGoogle ScholarPubMed
25. Ryan, D, Drysdale, AJ, Lafourcade, C, Pertwee, RG, Platt, B. Cannabidiol targets mitochondria to regulate intracellular Ca2+ levels. J Neurosci 2009;29:2053–2063. CrossRefGoogle ScholarPubMed
26. Weiss, L, Zeira, M, Reich, S et al. Cannabidiol arrests onset of autoimmune diabetes in NOD mice. Neuropharmacology 2008;54:244–249. CrossRefGoogle ScholarPubMed
27. Durst, R, Danenberg, H, Gallily, R et al. Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury. Am J Physiol Heart Circ Physiol 2007;293:3602–3607. CrossRefGoogle ScholarPubMed
28. Carlini, EA, Leite, JR, Tanhauser, M, Berardi, AC. Cannabidiol and Cannabis sativa extract protect mice and rats against convulsive agents. J Pharm Pharmacol 1973;25: 664–665. CrossRefGoogle ScholarPubMed
29. Izquierdo, I, Orsingher, OA, Berardi, AC. Effect of cannabidiol and other Cannabis sativa compounds on hippocampal seizures discharges. Psychopharmacology 1973; 28:95–102. CrossRefGoogle ScholarPubMed
30. Turkanis, SA, Cely, W, Olsen, DM, Karler, R. Anticonvulsant properties of cannabidiol. Res Commun Chem Pathol Pharmacol 1974;8:231–246. Google ScholarPubMed
31. Karniol, IG, Carlini, EA. Pharmacological interaction between cannabidiol and delta 9-tetrahydrocannabinol. Psychopharmacology 1973;3:53–70. CrossRefGoogle Scholar
32. Long, LE, Malone, DT, Taylor, DA. Cannabidiol reverses MK-801-induced disruption of prepulse inhibition in mice. Neuropsychopharmacology 2006;31:795–803. CrossRefGoogle ScholarPubMed
33. Moreira, FA, Aguiar, DC, Guimarães, FC. Anxiolyticlike effect of cannabidiol in the rat Vogel conflict test. Prog Neuropsychopharmacol Biol Psychiatry 2006;30:1466–1471. CrossRefGoogle ScholarPubMed
34. Zuardi, AW, Morais, SL, Guimarães, FS, Mechoulam, R. Antipsychotic effect of cannabidiol. J Clin Psychiatry 1995; 56:485–486. Google ScholarPubMed
35. Crippa, JA, Zuardi, AW, Garrido, GE et al. Effects of cannabidiol (CBD) on regional cerebral blood flow. Neuropsychopharmacol 2004;29:417–426. CrossRefGoogle ScholarPubMed
36. Fusar-Poli, P, Crippa, JA, Bhattacharyya, S et al. Distinct effects of delta-9-Tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatry 2009;66:95–105. CrossRefGoogle ScholarPubMed
37. Guimarães, FS, Chiaretti, TM, Graeff, FG, Zuardi, AW. Antianxiety effect of cannabidiol in the elevated plus-maze. Psychopharmacology 1990;100:558–559. CrossRefGoogle ScholarPubMed
38. Guimarães, FS, de Aguiar, JC, Mechoulam, R, Breuer, A. Anxiolytic effect of cannabidiol derivatives in the elevated plus-maze. Gen Pharmacol 1994;25:161–164. CrossRefGoogle ScholarPubMed
39. Zuardi, AW, Cosme, RA, Graeff, FG, Guimarães, FS. Effects of ipsapirone and cannabidiol on human experimental anxiety. J Psychopharmacol 1993;7:82–88. CrossRefGoogle ScholarPubMed
40. El-Alfy, AT, Ivey, K, Robinson, K et al. Antidepressant-like effect of Delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacol Biochem Behav 2010;95:434–442. CrossRefGoogle ScholarPubMed
41. Hill, MN, Gorzalka, BB. Enhancement of the anxiety-like response to the cannabinoid receptor agonist HU-210 following chronic stress. Eur J Pharmacol 2004;24:291–295. CrossRefGoogle Scholar
42. Hill, MN, Patel, S, Carrier, EJ et al. Dowregulation of endocannabinoid signaling in the hippocampus following chronic unpredictable stress. Neuropsychopharmacology 2005;30:508–515. CrossRefGoogle Scholar
43. Zanelati, TV, Biojone, C, Moreira, FA, Guimarães, FS, Joca, SR. Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors. Br J Pharmacol 2010;159:122–128. CrossRefGoogle Scholar
44. Russo, EB, Burbett, A, Hall, B, Parker, KK. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res 2005;30:1037–1043. CrossRefGoogle Scholar
45. Anderson, IM. Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a attenuates the effects of antidepressants on the forced swim test in rats. Brain Res 1996;709:215–220. Google Scholar
46. Joca, SR, Padovan, CM, Guimarães, FS. Stress, depression and the hippocampus. Rev Bras Psiquiatr 2003;2:46–51. CrossRefGoogle Scholar
47. Karege, F, Vaudan, G, Schwald, M, Perroud, N, La Harpe, R. Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs. Brain Res Mol Brain Res 2005;136: 29–37. CrossRefGoogle ScholarPubMed
48. Shirayama, Y, Chen, AC, Nakagawa, S, Russell, DS, Duman, RS. Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci 2002;22:3251–3261. CrossRefGoogle ScholarPubMed
49. Nibuya, M, Morinobu, S, Duman, RS. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 1995;15:7539–7547. CrossRefGoogle ScholarPubMed
50. Siuciak, JA, Lewis, DR, Wiegand, SJ, Lindsay, RM. Antidepressant-like effect of brain-derived neurotrophic factor (BDNF). Pharmacol Biochem Behav 1997;56:131–137. CrossRefGoogle ScholarPubMed
51. McArthur, R, Borsini, F. Animal models of depression in drug discovery: a historical perspective. Pharmacol Biochem Behav 2006;84:436–452. CrossRefGoogle ScholarPubMed
52. Detke, MJ, Rickels, M, Lucki, I. Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology 1995;121:66–72. CrossRefGoogle ScholarPubMed
53. Garcia, LB, Comim, CM, Valvassori, SS et al. Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:140–144. CrossRefGoogle ScholarPubMed
54. Garcia, LB, Comim, CM, Valvassori, SS et al. Chronic administration of ketamine elicits antidepressant-like effects in rats without affecting hippocampal brain-derived neurotrophic factor protein levels. Basic Clin Pharmacol Toxicol 2008;103:502–506. CrossRefGoogle ScholarPubMed
55. Porsolt, RD, Le Pichon, M, Jalfre, M. Animal model of depression. Nature 1977;266:730–732. CrossRefGoogle Scholar
56. Lowry, OH, Rosebough, NG, Farr, AL, Randall, RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–275. CrossRefGoogle ScholarPubMed
57. Patel, S, Cravatt, BF, Hillard, CJ. Synergistic interactions between cannabinoids and environmental stress in the activation of the central amygdalae. Neuropsychopharmacology 2005;30:497–507. CrossRefGoogle Scholar
58. Martin, M, Ledent, C, Parmentier, M, Maldonado, R, Valverde, O. Involvement of CB1 cannabinoid receptors in emotional behavior. Psychopharmacology 2002;159: 379–387. CrossRefGoogle Scholar
59. Carlson, G, Wang, Y, Alger, BE. Endocannabinoids facilitate the induction of LTP in the hippocampus. Nat Neurosci 2002;5:723–724. CrossRefGoogle ScholarPubMed
60. Fortunato, JJ, Réus, GZ, Kirsch, TR et al. Acute harmine administration induces antidepressive-like effects and increases BDNF levels in the rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:1425–1430. CrossRefGoogle ScholarPubMed
61. Réus, GZ, Stringari, RB, Kirsch, TR et al. Neurochemical and behavioural effects of acute and chronic memantine administration in rats: further support for NMDA as a new pharmacological target for the treatment of depression? Brain Res Bull 2010;81:585–589. CrossRefGoogle ScholarPubMed
62. Krishnan, V, Nestler, EJ. The molecular neurobiology of depression. Nature 2008;455:894–902. CrossRefGoogle ScholarPubMed
63. Aan het Rot, M, Mathew, SJ, Charney, DS. Neurobiological mechanisms in major depressive disorder. CMAJ 2009;180:305–313. CrossRefGoogle ScholarPubMed
64. Martinowich, K, Lu, B. Interaction between BDNF and serotonin: role in mood disorders. Neuropsychopharmacology 2008;33:73–83. CrossRefGoogle ScholarPubMed
65. Nestler, EJ, Barrot, M, DiLeone, RJ, Eisch, AJ, Gold, SJ, Monteggia, LM. Neurobiology of depression. Neuron 2002;34:13–25. CrossRefGoogle ScholarPubMed
66. Duman, RS, Monteggia, LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry 2006;59: 1116–1127. CrossRefGoogle ScholarPubMed
67. Larsen, MH, Hay-Schmidt, A, Ronn, LCB, Mikkelsen, JD. Temporal expression of brain-derived neurotrophic factor (BDNF) mRNA in the rat hippocampus after treatment with selective and mixed monoaminergic antidepressants. Eur J Psychopharmacol 2008;578:114–122. CrossRefGoogle ScholarPubMed
68. Kovaru, H, Pav, M, Kovaru, F, Raboch, J, Fiserova, A. Cell signalling in CNS and immune system in depression and during antidepressant treatment: focus on glial and natural killer cells. Neuro Endocrinol Lett 2009;30:421–428. Google ScholarPubMed
69. Yu, H, Chen, Z. The role of BDNF in depression on the basis of its location in the neural circuity. Acta Pharmacol Sin 2011;32:3–11. CrossRefGoogle Scholar
70. Vyas, A, Mitra, R, Shankaranarayana Rao, BS, Chattarji, S. Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J Neurosci 2002;22:6810–6818. CrossRefGoogle ScholarPubMed
71. Pawlak, R, Rao, BS, Melchor, JP, Chattarji, S, McEwen, B, Strickland, S. Tissue plasminogen activator and plasminogen mediate stressinduced decline of neuronal and cognitive functions in the mouse hippocampus. Proc Natl Acad Sci U S A 2005;102:18201–18206. CrossRefGoogle ScholarPubMed
72. Pizarro, JM, Lumley, LA, Medina, W et al. Acute social defeat reduces neurotrophin expression in brain cortical and subcortical areas in mice. Brain Res 2004;1025:10–20. CrossRefGoogle ScholarPubMed
73. Fanous, S, Hammer, RP Nikulina EM. Short- and long-term effects of intermittent social defeat stress on brain-derived neurotrophic factor expression in mesocorticolimbic brain regions. Neuroscience 2010;167:598–607. CrossRefGoogle Scholar
74. Murray, EA. The amygdala, reward and emotion. Trends Cogn Sci 2007;11:489–497. CrossRefGoogle ScholarPubMed
75. Lucca, G, Comim, CM, Valvassori, SS et al. Effects of chronic mild stress on the oxidative parameters in the rat brain. Neurochem Int 2009a;54:358–362. CrossRefGoogle ScholarPubMed
76. Lucca, G, Comim, CM, Valvassori, SS et al. Increased oxidative stress in submitochondrial particles into the brain of rats submitted to the chronic mild stress paradigm. J Psychiatr Res 2009b;43:864–869. CrossRefGoogle Scholar