Advertisement

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 391, Issue 3, pp 335–346 | Cite as

Omega-3 fatty acids supplementation with lithium and aripiprazole for improving the balance of circulating hormones and brain neurotransmitters in manic mice model

Original Article

Abstract

The present study was designed to evaluate the combined effect of lithium and aripiprazole supplemented with omega-3 fatty acids in methylphenidate (MPD)-induced manic mice. Swiss albino mice were administered with MPD or saline for 14 days, and based on changes in behavioral activities animals were treated with lithium, aripiprazole, and omega-3 fatty acids from the 8th day. Behavioral patterns were analyzed by video tracking. Thyroxine, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were assayed in serum using ELISA kits. The levels of neurotransmitters in the whole brain were analyzed spectrofluorometrically. Glycogen synthase kinase 3β (GSK3β) mice brain mRNA expression levels and phosphorylated Akt (pAkt) protein levels were measured using RT-PCR and western blot, respectively. Results indicated that the administration of MPD alters the behavioral activity, thyroid hormones, FSH, LH, and testosterone levels. Lithium, aripiprazole, and omega-3 fatty acids alone significantly reduced MPD-induced behavior, hormonal, and neurotransmitter abnormalities. However, GSK3β and pAkt in the brain showed no significant differences in the level of expression. These results reveal that the combination of lithium and aripiprazole supplemented with omega-3 fatty acids provide protective effects against MPD-induced neuroendocrine system and multiple neurochemical abnormalities.

Keywords

Mania Methylphenidate Open field test Thyroid hormone Dopamine Omega-3 fatty acids 

Notes

Acknowledgements

We wish to thank Annamalai University for the financial assistance with the award of a University Research Fellowship to Mr. P. Arunagiri.

Compliance with ethical standards

All experimental procedures were approved, and all the animals were cared for according to the Institutional Animal Ethics Committee of Rajah Muthiah Medical College and Hospital (Reg No. 160/1999/CPCSEA, Proposal number: 933) Annamalai Nagar Tamil Nadu, and India’s Animal Care Guidelines.

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. Anand A, Barkay G, Dzemidzic M, Albrecht D, Karne H, Zheng QH, Hutchins GD, Normandin MD, Yoder KK (2011) Striatal dopamine transporter availability in unmedicated bipolar disorder. Bipolar Disord 13(4):406–413.  https://doi.org/10.1111/j.1399-5618.2011.00936.x CrossRefPubMedGoogle Scholar
  2. Arunagiri P, Balamurugan E (2016) Omega-3 fatty acids combined with aripiprazole and lithium modulates activity of mitochondrial enzymes and acetylcholinesterase in methylphenidate-induced animal model of mania. PharmaNutrition 4(2):54–61.  https://doi.org/10.1016/j.phanu.2016.03.001 CrossRefGoogle Scholar
  3. Arunagiri P, Rajeshwaran K, Shanthakumar J, Tamilselvan T, Balamurugan E (2014) Combination of omega-3 fatty acids, lithium and aripiprazole reduces oxidative stress in brain of mice with mania. Boil Trace Elem Res 160(3):409–417.  https://doi.org/10.1007/s12011-014-0067-8 CrossRefGoogle Scholar
  4. Assie MB, Ravailhe V, Faucillon V, Newman-Tancredi A (2005) Contrasting contribution of 5-HT1A receptor activation to neurochemical profile of novel antipsychotics: frontocortical dopamine and hippocampal serotonin release in rat brain. J Pharmacol Exp Ther 315(1):265–272.  https://doi.org/10.1124/jpet.105.087163 CrossRefPubMedGoogle Scholar
  5. Barbosa FJ, Hesse B, de Almeida RB, Baretta IP, Boerngen-Lacerda R, Andreatini R (2011) Magnesium sulfate and sodium valproate block methylphenidate-induced hyperlocomotion, an animal model of mania. Pharmacol Rep 63(1):64–70.  https://doi.org/10.1016/S1734-1140(11)70399-1 CrossRefPubMedGoogle Scholar
  6. Barcelos RC, Benvegnú DM, Boufleur N, Reckziegel P, Müller LG et al (2009) Effects of omega-3 essential fatty acids [omega-3 EFAs] on motor disorders and memory dysfunction typical neuroleptic- induced: behavioral and biochemical parameter. Neurotox Res 17(3):228–237.  https://doi.org/10.1007/s12640-009-9095-0 CrossRefPubMedGoogle Scholar
  7. Bauer M, Heinz A, Whybrow PC (2002) Thyroid hormones, serotonin and mood: of synergy and significance in the adult brain. Mol Psychiatry 7(2):140–156.  https://doi.org/10.1038/sj.mp.4000963 CrossRefPubMedGoogle Scholar
  8. Beasley C, Cotter D, Everall I (2002) An investigation of the Wnt-signalling pathway in the prefrontal cortex in schizophrenia, bipolar disorder and major depressive disorder. Schizophr Res 58(1):63–67.  https://doi.org/10.1016/S0920-9964(01)00376-0 CrossRefPubMedGoogle Scholar
  9. Bilgiç A, Gürkan K, Türkoglu S (2007) Excessive masturbation and hypersexual behaviors associated with methylphenidate. J Am Acad Child Adolesc Psychiatry 46(7):789–790.  https://doi.org/10.1097/chi.0b013e318059360a CrossRefPubMedGoogle Scholar
  10. Bunney WEJ, Garland-Bunney BL (1987) Mechanisms of action of lithium in affective illness: basic and clinical implications. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven, New York, pp 553–565Google Scholar
  11. Chen G, Huang LD, Jiang YM, Manji HK (1999) The mood-stabilizing agent valproate inhibits the activity of glycogen synthase kinase-3. J Neurochem 72(3):1327–1330CrossRefPubMedGoogle Scholar
  12. Chomczynski P, Sacchi N (2006) The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: twenty-something years on. Nat Protoc 1(2):581–585.  https://doi.org/10.1038/nprot.2006.83 CrossRefPubMedGoogle Scholar
  13. Cutler A (2003) Sexual dysfunction and antipsychotic treatment. Psychoneuroendocrinology 28:69–82.  https://doi.org/10.1016/S0306-4530(02)00113-0 CrossRefPubMedGoogle Scholar
  14. Daban C, Vieta E, Mackin P, Young AH (2005) Hypothalamic-pituitary-adrenal axis and bipolar disorder. Psychiatr Clin North Am 28(2):469–480.  https://doi.org/10.1016/j.psc.2005.01.005 CrossRefPubMedGoogle Scholar
  15. Dinan G, Timothy C (2001) Psychoneuroendocrinology of mood disorders. Current Opinion in Psychiatry 14(1):51–55.  https://doi.org/10.1097/00001504-200101000-00009 CrossRefGoogle Scholar
  16. Findling RL (2008) Evolution of the treatment of attention- deficit/hyperactivity disorder in children: a review. Clin Ther 30(5):942–957.  https://doi.org/10.1016/j.clinthera.2008.05.006 CrossRefPubMedGoogle Scholar
  17. Gong SL, Wei J, Ramchand CN, Ramchand R, Hemmings GP (1993) Concentrations of homovanillic acid and gonadal hormones in the serum of male schizophrenic patients. Indian J Psychiatry 35:181–183PubMedPubMedCentralGoogle Scholar
  18. Greenwood TA, Alexander M, Keck PE, McElroy S, Sadovnick AD, Remick RA, Kelsoe JR (2001) Evidence for linkage disequilibrium between the dopamine transporter and bipolar disorder. Am J Med Genet 105(2):145–151.  https://doi.org/10.1002/1096-8628(2001)9999:9999<::AID-AJMG1161>3.0.CO;2-8 CrossRefPubMedGoogle Scholar
  19. Higgs BW, Elashoff M, Richman S, Barci B (2006) An online database for brain disease research. BMC Genomics 7(1):70.  https://doi.org/10.1186/1471-2164-7-70 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Janowsky DS, Overstreet DH (1995) The role of acetylcholine mechanisms in mood disorders. In: FE, Bloom., Kupfer, DJ [Eds.], Psychopharmacology. The fourth generation of progress. Raven, New York, pp 945–956Google Scholar
  21. Kelly B, Lundon D, McGuinness D, Brady C (2013) Methylphenidate-induced erections in a prepubertal child. J Pediatr Urol 9(1):e1–e2.  https://doi.org/10.1016/j.jpurol.2012.03.017 CrossRefPubMedGoogle Scholar
  22. Kishimoto T, De Hert M, Carlson HE, Manu P, Corrella CU (2012) Osteoporosis and fracture risk in people with schizophrenia. Current Opin Psychiatry 25(5):415–429.  https://doi.org/10.1097/YCO.0b013e328355e1ac CrossRefGoogle Scholar
  23. Kodas E, Galineau L, Bodard S, Vancassel S, Guilloteau D, Besnard JC, Chalon S (2004) Serotoninergic neurotransmission is affected by n-3 polyunsaturated fatty acids in the rat. J Neurochem 89(3):695–702.  https://doi.org/10.1111/j.1471-4159.2004.02401.x CrossRefPubMedGoogle Scholar
  24. Lesort M, Greendorfer A, Stockmeier C, Johnson GV, Jope RS (1999) Glycogen synthase kinase-3beta, beta-catenin, and tau in postmortem bipolar brain. J Neural Transm 106(11-12):1217–1222.  https://doi.org/10.1007/s007020050235 CrossRefPubMedGoogle Scholar
  25. Lowe IP, Robins E, Eyerman GS (1958) The fluorometric measurement of glutamic decarboxylase and its distribution in brain. J Neurochem 3(1):8–18.  https://doi.org/10.1111/j.1471-4159.1958.tb12604.x CrossRefPubMedGoogle Scholar
  26. Maes M, Bosmans E, Calabrese J, Smith R, Meltzer HY (1995) Interleukin-2 and interleukin-6 in schizophrenia and mania: effects of neuroleptics and mood stabilizers. J Psychiatr Res 29(2):141–152.  https://doi.org/10.1016/0022-3956(94)00049-W CrossRefPubMedGoogle Scholar
  27. Mavrikaki M, Nomikos GG, Panagis G (2010) Efficacy of the atypical antipsychotic aripiprazole in d-amphetamine-based preclinical models of mania. Int J Neuropsychopharmacol 13(04):541–548.  https://doi.org/10.1017/S1461145709991143 CrossRefPubMedGoogle Scholar
  28. Mazza M, Satta MA, Bria P, Mazza S (2004) Neuroendocrinology of mood disorders. Clin Ter 155(11-12):537–541PubMedGoogle Scholar
  29. Mcnamara RK, Jandacek R, Rider T, Tso P, Cole-strauss A, Lipton JW (2010) Omega-3 fatty acid deficiency increases constitutive pro-inflammatory cytokine production in rats : relationship with central serotonin turnover. Prostag Leukotr Ess 83(4-6):185–191.  https://doi.org/10.1016/j.plefa.2010.08.004 CrossRefGoogle Scholar
  30. Messamore E, McNamara RK (2016) Detection and treatment of omega-3 fatty acid deficiency in psychiatric practice: rationale and implementation. Lipids Health Dis 15(1):25.  https://doi.org/10.1186/s12944-016-0196-5 CrossRefPubMedPubMedCentralGoogle Scholar
  31. National Institutes of Health (2015) U. S. A Department of Health and Human Services, Depression (NIH Publication No. 15–3561). U.S. Government Printing Office, BethesdaGoogle Scholar
  32. Nemade R, Dombeck M. (2009) Bipolar disorder, neurochemistry and endocrinology in bipolar disorder. Ed by Patricelli K Mental Health & Substance Abuse Issues Aug 2009,Google Scholar
  33. Newcomer JW (2005) Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs 19:1–93CrossRefPubMedGoogle Scholar
  34. Nivoli AMA, Murru A, Goikolea JM, Crespo JM, Montes JM, González-pinto A, García- Portilla P, Bobes J, Sáiz-Ruiz J, Vieta E (2012) New treatment guidelines for acute bipolar mania: a critical review. J Affect Disord 140(2):125–141.  https://doi.org/10.1016/j.jad.2011.10.015 CrossRefPubMedGoogle Scholar
  35. Nogoceke FP, Barcaro IM, de Sousa DP, Andreatini R (2016) Antimanic-like effects of [R]-[-]-Carvone and [S]-[+]-Carvone in mice. Neurosci Lett 619:43–48.  https://doi.org/10.1016/j.neulet.2016.03.013. CrossRefPubMedGoogle Scholar
  36. Otero L, Zurita M, Aguayo C, Bonilla C, Rodríguez A, Vaquero J (2010) Video-Tracking-Box linked to Smart software as a tool for evaluation of locomotor activity and orientation in brain-injured rats. J Neurosci Methods 188(1):53–57.  https://doi.org/10.1016/j.jneumeth.2010.01.036 CrossRefPubMedGoogle Scholar
  37. Petty F (1995) GABA and mood disorders: a brief review and hypothesis. J Affect Disord 34(4):275–281.  https://doi.org/10.1016/0165-0327(95)00025-I CrossRefPubMedGoogle Scholar
  38. Post RM, Kramlinger KG, Joffe RT, Roy-Byrne PP, Rosoff A, Frye MA, Huggins T (1997) Rapid cycling bipolar affective disorder: lack of relation to hypothyroidism. Psychiatry Res 72(1):1–7.  https://doi.org/10.1016/S0165-1781(97)00076-0 CrossRefPubMedGoogle Scholar
  39. Prickaerts J, Moechars D, Cryns K, Lenaerts I, van Craenendonck H, Goris I, Daneels G, Bouwknecht JA, Steckler T (2006) Transgenic mice overexpressing glycogen synthase kinase 3beta: a putative model of hyperactivity and mania. J Neurosci 26(35):9022–9029.  https://doi.org/10.1523/JNEUROSCI.5216-05.2006 CrossRefPubMedGoogle Scholar
  40. Rainka MM, Capote HA, Ross CA, Gengo FM (2009) Attenuation of risperidone-induced hyperprolactinemia with the addition of aripiprazole. J Clin Pharm Ther 34(5):595–598.  https://doi.org/10.1111/j.1365-2710.2008.01009.x CrossRefPubMedGoogle Scholar
  41. Saravanakumar A, Gandhimathi R (2009) Effect of Guettarda speciosa extracts on biogenic amines concentrations in rat brain after induction of seizure. Int J Phar Pharmaceutical Sci 1:1Google Scholar
  42. Schwarz MJ, Myint AM, Opgen-Rhein M, Musil R, Spellmann I, Riedel M (2008) Relationship between serum aripiprazole, dehydroaripiprazole, prolactin and testosterone concentrations and clinical response to aripiprazole in male schizophrenic patients. Pharmacopsychiatry 41:A30CrossRefGoogle Scholar
  43. Siesser WB, Cheng SY, McDonald MP (2005) Hyperactivity, impaired learning on a vigilance task, and a differential response to methylphenidate in the TR beta PV knock-in mouse. Psychopharmacology 181(4):653–663.  https://doi.org/10.1007/s00213-005-0024-5 CrossRefPubMedGoogle Scholar
  44. Silambarasan T, Manivannan J, Priya K, Suganya N, Chatterjee S, Raja B (2014) Sinapic acid prevents hypertension and cardiovascular remodeling in pharmacological model of nitric oxide inhibited rats. PLoS One 9(12):e115682.  https://doi.org/10.1371/journal.pone. 0115682 CrossRefPubMedPubMedCentralGoogle Scholar
  45. Souza LS, Silva EF, Santos WB, Asth L, Lobão-Soares B, Soares-Rachetti VP, Medeiros IU, Gavioli EC (2016) Lithium and valproate prevent methylphenidate-induced mania- like behaviors in the hole board test. Neurosci Lett 629:143–148.  https://doi.org/10.1016/j.neulet.2016.06.044 CrossRefPubMedGoogle Scholar
  46. Souza LL, Cordeiro A, Oliveira LS, de Paula GS, Faustino LC, Ortiga-Carvalho TM et al (2011) Thyroid hormone contributes to the hypolipidemic effect of polyunsaturated fatty acids from fish oil?: in vivo evidence for cross talking mechanisms. J Endocrinol 211(1):65–72.  https://doi.org/10.1530/JOE-11-0142 CrossRefPubMedGoogle Scholar
  47. Tamilselvan T, Siddique SA, Vishnupriya M, Sindhu G, Balamurugan E (2017) Behavioral and neurochemical evaluation of ethanol on olanzapine treated methylphenidate induced manic like behaviors in swiss albino mice. BJBAS 6:48–56.  https://doi.org/10.1016/j.bjbas.2017.01.001 Google Scholar
  48. Tanaka K, Farooqui AA, Siddiqi NJ, Alhomida AS, Ong W-Y (2012) Effects of docosahexaenoic acid on neurotransmission. Biomol Ther (Seoul). Mar 20(2):152–157Google Scholar
  49. Yang P, Singhal N, Modi G, Swann A, Dafny N (2001) Effects of lithium chloride on induction and expression of methylphenidate sensitization. Eur J Pharmacol 426(1-2):65–72.  https://doi.org/10.1016/S0014-2999(01)01213-4 CrossRefPubMedGoogle Scholar
  50. Young JW, Goey AKL, Arpi M, Perry W, Paulus MP, Geyer MA (2010) GBR 12909 administration as a mouse model of bipolar disorder mania: mimicking quantitative assessment of manic behavior. Psychopharmacology 208(3):443–454.  https://doi.org/10.1007/s00213-009-1744-8 CrossRefPubMedGoogle Scholar
  51. Zhang Z, Li Q, Kang W, Tan Q, Gao C et al (2006) Differences in hypothyroidism between lithium-free and-treated patients with bipolar disorders. Life Sci 78(7):771–776.  https://doi.org/10.1016/j.lfs.2005.05.090 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai UniversityAnnamalainagarIndia
  2. 2.Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health SciencesUniversity of KwaZulu-NatalDurbanSouth Africa

Personalised recommendations