Advertisement

Lacidipine attenuates reserpine-induced depression-like behavior and oxido-nitrosative stress in mice

  • Kunal Khurana
  • Nitin BansalEmail author
Original Article
  • 3 Downloads

Abstract

Depression is a serious medical illness displaying high lifetime prevalence, early-age onset that adversely affects socio-economic status. The bidirectional association between oxidative stress and calcium-signaling adversely affects the monoaminergic neuron functions that instigate the pathogenesis of depression. The present study investigates the effect of lacidipine (LCD), L-type Ca2+-channel blocker, on reserpine-induced depression in mice. Separate groups of mice (Swiss albino, 18–25 g) were administered lacidipine (0.3, 1 and 3 mg/kg, i.p.) daily for 14 days and reserpine (5 mg/kg, i.p.) was injected on day 14. Rectal temperature, catalepsy, and tail-suspension test (TST) were performed 18 h and ptosis scores at 60, 120, 240, 360 min post-reserpine treatment. Whole-brain TBARS, GSH, nitrite, and superoxide dismutase (SOD) and catalase activities were estimated. Reserpine elevated the catalepsy, ptosis, hypothermia, and immobility period in TST owing to the marked increase in oxidative-nitrosative stress in the brain of mice. LCD attenuated the reserpine triggered the rise in catalepsy, ptosis scores, hypothermia, and immobility period in mice. LCD pretreatment attenuated the increase in TBARS and nitrite levels, and the decline of GSH, SOD, and catalase activities in the brain of reserpine injected mice. Bay-K8644 (0.5 mg/kg, i.p.), Ca2+-channel agonist, attenuated these effects of LCD (3 mg/kg) in reserpine-treated mice. It can be inferred that lacidipine (Ca2+ channel antagonist) attenuates depression-like symptoms in reserpine-treated mice. Furthermore, the abrogation of antidepressant-like effects of LCD by Bay-K8644 revealed that modulation of Ca2+-channels might present a potential strategy in the management of depression.

Keywords

Lacidipine Depression Calcium channel Oxidative stress Reserpine 

Notes

Acknowledgements

The authors are thankful to I. K. Gujral Punjab Technical University, Kapurthala (India) and ASBASJSM College of Pharmacy, Bela (Ropar), Punjab, India for providing the necessary facilities for carrying out research work.

Authors’ contribution

Prof. (Dr.) Nitin Bansal designed this study. Kunal Khurana (Ph.D. Research scholar) conducted the research and analyzed and interpreted the data. Both authors wrote the initial and final drafts of the article.

Compliance with ethical standards

The experimental protocol was approved by the Institutional Animal Ethics Committee (ASCB/IAEC/08/15/108).

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Aburawi S, Al-Tubuly R, Alghzewi E, Gorash Z (2007) Effects of calcium channel blockers on antidepressant action of alprazolam and imipramine. Libyan J Med 2(4):169–175.  https://doi.org/10.4176/070909 CrossRefGoogle Scholar
  2. Ahmed HH, Abd El Dayem SM, Aly Foda FM, Mohamed HA (2015) Significance of vitamin D in combination with calcium in modulation of depression in the experimental model. Der Pharma Chemica 7:128–147Google Scholar
  3. Arora V, Kuhad A, Tiwari V, Chopra K (2011) Curcumin ameliorates reserpine-induced pain-depression dyad: behavioural, biochemical, neurochemical and molecular evidences. Psychoneuroendocrinology 36(10):1570–1581.  https://doi.org/10.1016/j.psyneuen.2011.04.012 CrossRefGoogle Scholar
  4. Askew BM (1963) A simple screening procedure for imipramine-like antidepressant agents. Life Sci 2(10):725–730.  https://doi.org/10.1016/0024-3205(63)90076-6 CrossRefGoogle Scholar
  5. Bellosta S, Canavesi M, Favari E, Cominacini L, Gaviraghi G, Fumagalli R, Paoletti R, Bernini F (2001) Lacidipine modulates the secretion of matrix metalloproteinase-9 by human macrophages. J Pharmacol Exp Ther 296(3):736–743Google Scholar
  6. Bergantin LB, Caricati-Neto A (2016) Impact of interaction of Ca2+/cAMP intracellular signalling pathways in clinical pharmacology and translational medicine. Clin Pharmacol Transl Med 1(1):2–5Google Scholar
  7. Berkels R, Breitenbach T, Bartels H, Taubert D, Rosenkranz A, Klaus W, Roesen R (2005) Different antioxidative potencies of dihydropyridine calcium channel modulators in various models. Vasc Pharmacol 42(4):145–152.  https://doi.org/10.1016/j.vph.2004.11.003 CrossRefGoogle Scholar
  8. Cao X, Wei Z, Gabriel GG, Li X, Mousseau DD (2007) Calcium-sensitive regulation of monoamine oxidase-a contributes to the production of peroxyradicals in hippocampal cultures: implications for Alzheimer disease-related pathology. BMC Neurosci 8:73CrossRefGoogle Scholar
  9. Claiborne A (1985) Catalase activity. In: Greenwald RA (ed) CRC handbook of methods for oxygen radical research, 3rd edn. CRC, Boca Raton, pp 283–284Google Scholar
  10. Costall B, Naylor RJ (1974) On catalepsy and catatonia and the predictability of the catalepsy test for neuroleptic activity. Psychopharmacologia 34(3):233–241CrossRefGoogle Scholar
  11. Deak F, Lasztoczi B, Pacher P, Petheo GL, Kecskemeti V, Spat A (2000) Inhibition of voltage-gated calcium channels by fluoxetine in rat hippocampal pyramidal cells. Neuropharmacology 39(6):1029–1036.  https://doi.org/10.1016/S0028-3908(99)00206-3 CrossRefGoogle Scholar
  12. Dhingra D, Valecha R (2007) Evaluation of the antidepressant-like activity of Convolvulus pluricaulischoisy in the mouse forced swim and tail suspension tests. Med Sci Monit 13(7):BR155–BR161Google Scholar
  13. Dhir A, Kulkarni SK (2011) Nitric oxide and major depression. Nitric Oxide 24(3):125–131.  https://doi.org/10.1016/j.niox.2011.02.002 CrossRefGoogle Scholar
  14. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82(1):70–77.  https://doi.org/10.1016/0003-9861(59)90090-6 CrossRefGoogle Scholar
  15. Guan LP, Liu BY (2016) Antidepressant-like effects and mechanisms of flavonoids and related analogues. Eur J Med Chem 121:47–57.  https://doi.org/10.1016/j.ejmech.2016.05.026 CrossRefGoogle Scholar
  16. Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97(6):1634–1658.  https://doi.org/10.1111/j.1471-4159.2006.03907.x CrossRefGoogle Scholar
  17. Hasler G (2010) Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World Psychiatry 9:155–161.  https://doi.org/10.1002/j.2051-5545.2010.tb00298.x CrossRefGoogle Scholar
  18. Jackson KJ, Damaj MI (2009) L-type calcium channels and calcium/calmodulin-dependent kinase II differentially mediate behaviors associated with nicotine withdrawal in mice. J Pharmacol Exp Ther 330(1):152–161.  https://doi.org/10.1124/jpet.109.151530 CrossRefGoogle Scholar
  19. Joca SR, Guimaraes FS (2006) Inhibition of neuronal nitric oxide synthase in the rat hippocampus induces antidepressant-like effects. Psychopharmacology 185(3):298–305.  https://doi.org/10.1007/s00213-006-0326-2 CrossRefGoogle Scholar
  20. Kumar M, Bansal N (2018) Ellagic acid prevents dementia through modulation of PI3-kinase-endothelial nitric oxide synthase signalling in streptozotocin-treated rats. Naunyn Schmiedeberg's Arch Pharmacol 391(9):987–1001.  https://doi.org/10.1007/s00210-018-1524-2 CrossRefGoogle Scholar
  21. Kumbasar S, Yapca OE, Bilen H, Suleyman B, Ozgeris FB, Borekci B, Suleyman H (2012) The effect of Lacidipine on ischemia-reperfusion induced oxidative damage in ovaries of female rats. Biomed Res 23(4):495–500Google Scholar
  22. Liu T, Zhong S, Liao X, Chen J, He T, Lai S, Jia Y (2015) A meta-analysis of oxidative stress markers in depression. PLoS One 10(10):e0138904.  https://doi.org/10.1371/journal.pone.0138904 CrossRefGoogle Scholar
  23. Lohr JB, Kuczenski R, Niculescu AB (2003) Oxidative mechanisms and tardive dyskinesia. CNS Drugs 17(1):47–62.  https://doi.org/10.2165/00023210-200317010-00004 CrossRefGoogle Scholar
  24. Lowry OH, Rosebrough NJ, Farr A, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275Google Scholar
  25. Maes M, Fišar Z, Medina M, Scapagnini G, Nowak G, Berk M (2012) New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates--Nrf2 activators and GSK-3 inhibitors. Inflammopharmacology Jun 20(3):127–150.  https://doi.org/10.1007/s10787-011-0111-7 CrossRefGoogle Scholar
  26. McCormack PL, Wagstaff AJ (2003) Lacidipine: a review of its use in the management of hypertension. Drugs 63(21):2327–2356.  https://doi.org/10.2165/00003495-200363210-00008 CrossRefGoogle Scholar
  27. Nemeroff CB (2007) The burden of severe depression: a review of diagnostic challenges and treatment alternatives. J Psychiatr Res 41(3–4):189–206.  https://doi.org/10.1016/j.jpsychires.2006.05.008 CrossRefGoogle Scholar
  28. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358.  https://doi.org/10.1016/0003-2697(79)90738-3 CrossRefGoogle Scholar
  29. Paul IA (2001) Antidepressant activity and calcium signaling cascades. Hum Psychopharmacol 16(1):71–80.  https://doi.org/10.1002/hup.186 CrossRefGoogle Scholar
  30. Prakhie IV, Oxenkrug GF (1998) The effect of nifedipine, Ca(2+) antagonist, on activity of MAO inhibitors, N-acetylserotonin and melatonin in the mouse tail suspension test. Int J Neuropsychopharmacol 1(1):35–40.  https://doi.org/10.1017/S1461145798001096 CrossRefGoogle Scholar
  31. Ried LD, Tueth MJ, Handberg E, Kupfer S, Pepine CJ, INVEST Study Group (2005) A study of antihypertensive drugs and depressive symptoms (SADD-Sx) in patients treated with a calcium antagonist versus an atenolol hypertension treatment strategy in the International Verapamil SR-Trandolapril study (INVEST). Psychosom Med 67(3):398–406.  https://doi.org/10.1097/01.psy.0000160468.69451.7f CrossRefGoogle Scholar
  32. Ried LD, Tueth MJ, Taylor MD, Sauer BC, Lopez LM, Pepine CJ (2006) Depressive symptoms in coronary artery disease patients after hypertension treatment. Ann Pharmacother Apr 40(4):597–604. Epub 2006 Mar 28.  https://doi.org/10.1345/aph.1G438 CrossRefGoogle Scholar
  33. Rubin B, Malone MH, Waugh MH, Burke JC (1957) Bioassay of Rauwolfia roots and alkaloids. J Pharmacol Exp Ther 120(2):125–136Google Scholar
  34. Salido GM (2009) Oxidative stress, intracellular calcium signals and apoptotic processes. In: Salido GM, Rosado JA (eds) Apoptosis: involvement of oxidative stress and intracellular Ca2+ homeostasis, 1st edn. Springer, Dordrecht, pp 1–16CrossRefGoogle Scholar
  35. Sastry KV, Moudgal RP, Mohan J, Tyagi JS, Rao GS (2002) Spectrophotometric determination of serum nitrite and nitrate by copper-cadmium alloy. Anal Biochem 306(1):79–82.  https://doi.org/10.1006/abio.2002.5676 CrossRefGoogle Scholar
  36. Siwek M, Sowa-Kućma M, Dudek D, Styczeń K, Szewczyk B, Kotarska K, Misztakk P, Pilc A, Wolak M, Nowak G (2013) Oxidative stress markers in affective disorders. Pharmacol Rep 65(6):1558–1571.  https://doi.org/10.1016/S1734-1140(13)71517-2 CrossRefGoogle Scholar
  37. Spiers JG, Chen HJ, Sernia C, Lavidis NA (2015) Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress. Front Neurosci 8:456.  https://doi.org/10.3389/fnins.2014.00456 CrossRefGoogle Scholar
  38. Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85(3):367–370.  https://doi.org/10.1007/BF00428203 CrossRefGoogle Scholar
  39. van Amsterdam FT, Roveri A, Maiorino M, Ratti E, Ursini F (1992) Lacidipine: a dihydropyridine calcium antagonist with antioxidant activity. Free Radic Biol Med 12(3):183–187.  https://doi.org/10.1016/0891-5849(92)90025-C CrossRefGoogle Scholar
  40. Vavakova M, Durackova Z, Trebaticka J (2015) Markers of oxidative stress and neuroprogression in depression disorder. Oxidative Med Cell Longev 2015(898393):112.  https://doi.org/10.1155/2015/898393 CrossRefGoogle Scholar
  41. Winterbourn CC, Hawkins RE, Brian M, Carrell RW (1975) The estimation of red cell superoxide dismutase activity. J Lab Clin Med 85(2):337–341Google Scholar
  42. Wultsch T, Chourbaji S, Fritzen S, Kittel S, Grünblatt E, Gerlach M, Gutknecht L, Chizat F, Golfier G, Schmitt A, Gass P, Lesch KP, Reif A (2007) Behavioural and expressional phenotyping of nitric oxide synthase-I knockdown animals. J Neural Transm Suppl 72:69–85.  https://doi.org/10.1007/978-3-211-73574-9_10 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.I. K. Gujral Punjab Technical UniversityKapurthalaIndia
  2. 2.Department of PharmacologyASBASJSM College of PharmacyBela (Ropar)India

Personalised recommendations