Effects of melatonin and agomelatine on doxorubicin induced anxiety and depression-like behaviors in rats

Yıl 2018, Cilt: 5 Sayı: 7, 253 - 259, 30.07.2018

Hatice Aygun , Serdar Savas Gul

https://doi.org/10.17546/msd.433289

Cited By: 1

Öz

Objective:  Doxorubicin (DOX) is a
chemotherapeutic agent used to treat several cancer types; however, it
exhibits severe side effects in the nervous system which DOX treatment evoked
neurobehavioral alterations such as anxiety and depressive-like behavior. We
investigated the use of melatonin and agomelatine to prevent neurobehavioral
alterations caused by DOX.

Material and Methods: Forty-nine Wistar albino rats were
randomly divided into 7 groups, namely control (CON, n=7), doxorubicin (DOX,
n=7), melatonin (MEL, n=7), agomelatine (AGO, n=7), melatonin + doxorubicin
(MEL + DOX, n=7), agomelatine + doxorubicin (AGO + DOX, n=7) melatonin +
agomelatine + doxorubicin (MEL + AGO + DOX, n=7) groups. Doxorubicin (18 mg/kg)
was injected intraperitoneally (i.p) on the 5th, 6th, 7th day of the study.
Animals were treated with melatonin (40 mg/kg/i.p), agomelatine (40
mg/kg/i.p), melatonin (40 mg/kg/i.p) + agomelatine (40 mg/kg/i.p), for 7 days
and then doxorubicin (18 mg/kg/i.p) was injected on the 5th, 6th, 7th day. On
the 8th day of the experiment, all animal evaluated open field test (OFT) and
forced swim test (FST) respectively.

Results: The only DOX-treated rats exhibited the reduced
exploration, grooming, and locomotor activity in the open field test and
increased immobility time, reduced swimming time. Our data showed that the
rats treated with DOX exhibited anxiety and depressive-like behavior.
Melatonin and agomelatine treatment reduced all the parameters of DOX-induced
anxiety and depressive-like behavior in rats.

Conclusions: Melatonin and agomelatine have a protective
effect of against DOX-induced neurobehavioral alterations in rats.

Anahtar Kelimeler

: doxorubicin, melatonin, agomelatine, rat, anxiety, depression

Kaynakça

• 1. Pal SK, Hurria A. Impact of age, sex, and comorbidity on cancer therapy and disease progression. J Clin Oncol Off J Am Soc Clin Oncol 2010; 28: 4086–4093.
• 2. Davison SN, Jhangri GS. The relationship between spirituality, psychosocial adjustment to illness, and health-related quality of life in patients with advanced chronic kidney disease. J Pain Symptom Manag 2013; 45: 170–178.
• 3. Quiles JL, Huertas JR, Battino M, Mataix J, Ramirez-Tortosa MC. Antioxidant nutrients and adriamycin toxicity. Toxicology 2002; 180: 79–95.
• 4. Booser DJ, Hortobagyi GN. Anthracycline antibiotics in cancer therapy. Focus on drug resistance. Drugs 1994; 47: 223-58.
• 5. Cutts SM, Swift LP, Rephaeli A, Nudelman A, Phillips DR. Sequence specificity of adriamycin-DNA adducts in human tumor cells. Mol Cancer Ther 2003; 2: 661–670.
• 6. Wefel JS, Witgert ME, Meyers CA. Neuropsychological sequelae of non-central nervous system cancer and cancer therapy. Neuropsychol Rev 2008; 18: 121–131.
• 7. Carvalho C1, Santos RX, Cardoso S, Correia S, Oliveira PJ, Santos MS, Moreira PI Doxorubicin: the good, the bad and the ugly effect. Curr Med Chem 2009; 16: 3267–3285.
• 8. Jansen CE, Dodd MJ, Miaskowski CA, Dowling GA, Kramer J. Preliminary results of a longitudinal study of changes in cognitive function in breast cancer patients undergoing chemotherapy with doxorubicin and cyclophosphamide. Psychooncology 2008; 17: 1189–1195.
• 9. Kwatra M, Kumar V, Jangra A, Mishra M, Ahmed S, Ghosh P, Vohora D, Khanam R. Ameliorative effect of naringin against doxorubicin-induced acute cardiac toxicity in rats. Pharm Biol 2016; 54: 637–647.
• 10. Merzoug S, Toumi ML, Boukhris N, Baudin B, Tahraoui A. Adriamycinrelated anxiety-like behavior, brain oxidative stress and myelotoxicity in male Wistar rats. Pharmacol Biochem Behav 2011; 99: 639–647.
• 11. Merzoug S, Toumi ML, Tahraoui A. Quercetin mitigates adriamycin-induced anxiety-and depression-like behaviors, immune dysfunction, and brain oxidative stress in rats. Naunyn Schmiedebergs Arch Pharmacol 2014; 387: 921–933.
• 12. Demyttenaere K. Agomelatine: a narrative review. Eur Neuropsychopharmacol 2011; 4: 703–709.
• 13. Delagrange P, Boutin JA. Therapeutic potential of melatonin ligands. Chronobiol Int 2006; 23: 413–418.
• 14. Aygun H, Aydin D, Inanir S, Ekici F, Ayyildiz M, Agar E. The effects of agomelatine and melatonin on ECoG activity of absence epilepsy model in WAG/Rij rats. Turkish J Biology 2015; 39: 904-910.
• 15. Leeboonngam T, Pramong R, Sae Ung K, Govitrapong P, Phansuwan Pujito. Neuroprotective effects of melatonin on amphetamine-induced dopaminergic fiber degeneration in the hippocampus of postnatal rats. J Pineal Res 2017; 64: 1-19.
• 16. Gomaa AM, Galal HM, Abou-Elgait AT. Neuroprotective effects of melatonin administration against chronic immobilization stress in rats. Int J Physiol Pathophysiol Pharmacol 2017; 9: 16–27.
• 17. Sáenz JCB, Villagra OR, Trías JF. Factor analysis of forced swimming test, sucrose preference test and open field test on enriched, social and isolated reared rats. Behav Brain Res 2006; 169: 57–65.
• 18. Molina-Hernández M, Tellez-Alcántara NP, Garcí JP, Lopez JIO, Jaramillo MT. Synergistic interaction between ketoconazole and several antidepressant drugs with allopregnanolone treatments in ovariectomized Wistar rats forced to swim. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 1337–1345.
• 19. Sarkisova KY, Midzianovskaia IS, Kulikov MA. Depressive-like behavioral alterations and c-fos expression in the dopaminergic brain regions in WAG/Rij rats with genetic absence epilepsy. Behav Brain Res 2003; 144: 211-226.
• 20. Sarkisova KY, Kulikov MA. Behavioral characteristics of WAG/Rij rats susceptible and non-susceptible to audiogenic seizures. Behav Brain Res 2006; 166: 9–18.
• 21. Willner P, Mitchell PJ. The validity of animal models of predisposition to depression. Behav Pharmacol 2002; 3: 169–188.
• 22. Kalueff AV, Lou YR, Laaksi I, Tuohimaa P. Increased anxiety in mice lacking vitamin D receptor gene. Neuroreport 2004; 15: 1271–1274.
• 23. Kalueff AV, Lou YR, Laaksi I, Tuohimaa P. Abnormal behavioral organization of grooming in mice lacking the vitamin D receptor gene. J Neurogenet 2005; 19: 1–24.
• 24. Zou J, Minasyan A, Keisala T, Zhang Y, Wang JH, Lou YR, Kalueff A, Pyykkö I, Tuohimaa P. Progressive hearing loss in mice with a mutated vitamin D receptor gene. Audiol Neurootol 2008; 13: 219–230.
• 25. Lopez-Rubalcava C, Lucki I. Strain differences in the behavioral effects of antidepressant drugs in the rat forced swimming test. Neuropsychopharmacology 2000; 22: 191–199.
• 26. Rocha PDSD, Campos JF, Nunes-Souza V, Vieira MDC, Boleti APA, Rabelo LA, Dos Santos EL, de Picoli Souza K. Antioxidant and protective effects of schinus terebinthifolius raddi against doxorubicin-induced toxicity. Appl Biochem Biotechnol 2017; 184: 869-884.
• 27. Konat GW, Kraszpulski M, James I, Zhang HT, Abraham J. Cognitive dysfunction induced by chronic administration of common cancer chemotherapeutics in rats. Metab Brain Dis 2008; 23: 325–333.
• 28. Liedke PE, Reolon GK, Kilpp B, Brunetto AL, Roesler R, Schwartsmann G. Systemic administration of doxorubicin impairs aversively motivated memory in rats. Pharmacol Biochem Behav 2009; 94: 239–243.
• 29. Joshi G, Sultana R, Tangpong J, Cole MP, St Clair DK, Vore M, Estus S, Butterfield DA. Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin: insight into chemobrain. Free Radic Res 2005; 39: 1147-1154.
• 30. Joshi G, Hardas S, Sultana R, St Clair DK, Vore M, Butterfield DA. Glutathione elevation by gamma-glutamyl cysteine ethyl ester as a potential therapeutic strategy for preventing oxidative stress in brain mediated by in vivo administration of adriamycin: implication for chemobrain. J Neurosci Res 2007; 85: 497–503.
• 31. Tangpong J, Cole MP, Sultana R, Joshi G, Estus S, Vore M, St Clair W, Ratanachaiyavong S, St Clair DK, Butterfield DA. Adriamycin-induced TNF-α-mediated central nervous system toxicity. Neurobiol Dis 2006; 23: 127–139.
• 32. Tangpong J, Cole MP, Sultana R, Estus S, Vore M, St Clair W, Ratanachaiyavong S, St Clair DK, Butterfield DA. Adriamycin-mediated nitration of manganese superoxide dismutase in the central nervous system: insight into the mechanism of chemobrain. J Neurochem 2007; 100: 191–201.
• 33. Dubovický M. Neurobehavioral manifestations of developmental impairment of the brain. Interdiscip Toxicol 2010; 3: 59–67.
• 34. Bains JS, Shaw CA. Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res Rev 1997; 25: 335-358.
• 35. Montilla P, Tunez I, Munoz MC, Soria JV, Lopez A. Antioxidative effect of melatonin in rat brain oxidative stress induced by adriamycin. Rev Esp Fisiol 1997; 53: 301–305.
• 36. Hill MN, Brotto LA, Lee TT, Gorzalka BB. Corticosterone attenuates the antidepressant-like effects elicited by melatonin in the forced swim test in both male and female rats, Prog. Neuro-Psychopharmacol. Biol Psychiatry 2003; 27: 905–911.
• 37. Micale V, Arezzi A, Rampello L, Drago F. Melatonin affects the immobility time of rats in the forced swim test: the role of serotonin neurotransmission. Eur Neuropsychopharmacol 2006; 16: 538–545.
• 38. Overstreet DH, Pucilowski O, Retton MC, Delagrange P, Guardiola-Lemaitre B. Effects of melatonin receptor ligands on swim test immobility. Neuroreport 1998; 9: 249-253.
• 39. Liu J, Clough SJ, Dubocovich ML. Role of the MT1 and MT2 melatonin receptors in mediating depressive and anxiety-like behaviors in C3H/HeN mice. Genes Brain Behav 2017; 16: 546-553.
• 40. Dagyte G, Luiten PG, De Jager T, Gabriel C, Mocaër E, Den Boer JA, Van der Zee EA. Chronic stress and antidepressant agomelatine induce region‐specific changes in synapsin I expression in the rat brain. J Neurosci Res 2011; 89(10): 1646-1657.
• 41. Reagan LP, Reznikov LR, Evans AN, Gabriel C, Mocaër E, Fadel JR. The antidepressant agomelatine inhibits stress-mediated changes in amino acid efflux in the rat hippocampus and amygdala. Brain Res 2012; 1466: 91-98.
• 42. Andreasson A, Arborelius L, Erlanson-Albertsson C, Lekander M. A putative role for cytokines in the impaired appetite in depression. Brain Behav Immun 2007; 21: 147–152.
• 43. Cyranowski JM, Marsland AL, Bromberger JT, Whiteside TL, Chang Y, Matthews KA. Depressive symptoms and production of proinflammatory cytokines by peripheral blood mononuclear cells stimulated in vitro. Brain Behav Immun 2007; 21:229–237.
• 44. Demirdaş A, Nazıroğlu M, Ünal GÖ. Agomelatine reduces brain, kidney, and liver oxidative stress but increases plasma cytokine production in the rats with chronic mild stress-induced depression. Metab Brain Dis 2016; 31(6): 1445-1453.