Metabolic Brain Disease

, Volume 33, Issue 2, pp 467–480 | Cite as

Garcinia mangostana Linn displays antidepressant-like and pro-cognitive effects in a genetic animal model of depression: a bio-behavioral study in the Flinders Sensitive Line rat

  • Inge Oberholzer
  • Marisa Möller
  • Brendan Holland
  • Olivia M. Dean
  • Michael Berk
  • Brian H. Harvey
Original Article


There is abundant evidence for both disorganized redox balance and cognitive deficits in major depressive disorder (MDD). Garcinia mangostana Linn (GM) has anti-oxidant activity. We studied the antidepressant-like and pro-cognitive effects of raw GM rind in Flinders Sensitive Line (FSL) rats, a genetic model of depression, following acute and chronic treatment compared to a reference antidepressant, imipramine (IMI). The chemical composition of the GM extract was analysed for levels of α- and γ-mangostin. The acute dose-dependent effects of GM (50, 150 and 200 mg/kg po), IMI (20 mg/kg po) and vehicle were determined in the forced swim test (FST) in FSL rats, versus Flinders Resistant Line (FRL) control rats. Locomotor testing was conducted using the open field test (OFT). Using the most effective dose above coupled with behavioral testing in the FST and cognitive assessment in the novel object recognition test (nORT), a fixed dose 14-day treatment study of GM was performed and compared to IMI- (20 mg/kg/day) and vehicle-treated animals. Chronic treated animals were also assessed with respect to frontal cortex and hippocampal monoamine levels and accumulation of malondialdehyde. FSL rats showed significant cognitive deficits and depressive-like behavior, with disordered cortico-hippocampal 5-hydroxyindole acetic acid (5-HIAA) and noradrenaline (NA), as well as elevated hippocampal lipid peroxidation. Acute and chronic IMI treatment evoked pronounced antidepressant-like effects. Raw GM extract contained 117 mg/g and 11 mg/g α- and γ-mangostin, respectively, with acute GM demonstrating antidepressant-like effects at 50 mg/kg/day. Chronic GM (50 mg/kg/d) displayed significant antidepressant- and pro-cognitive effects, while demonstrating parity with IMI. Both behavioral and monoamine assessments suggest a more prominent serotonergic action for GM as opposed to a noradrenergic action for IMI, while both IMI and GM reversed hippocampal lipid peroxidation in FSL animals. Concluding, FSL rats present with cognitive deficits and depressive-like behaviors that are reversed by acute and chronic GM treatment, similar to that of IMI.


Ethnopharmacology Mangosteen Oxidative stress Inflammation Chromatographic fingerprinting Psychiatry 



The authors would like to thank Hylton Bunting and Antoinette Fick for their assistance in the breeding and welfare of the animals. The authors would also like to thank Dr Dewet Wolmarans for assistance with analyzing the nORT data, Dr Makhotso Lekhooa for valuable insights into the writing of the paper, and Trent Ashton (Deakin University, Australia) for assisting with the chromatographic fingerprinting of GM. We also acknowledge Walter Dreyer and Francois Viljoen for their assistance during the ELISA and HPLC analyses, respectively.

Sources of funding

The authors declare that this work has been funded by the South African National Research Foundation (BHH; grant number 77323). The grant-holder acknowledges that opinions, findings and conclusions or recommendations expressed in any publication generated by NRF supported research are those of the authors, and that the NRF accepts no liability whatsoever in this regard. This funder had no other role in the study. MB is supported by a NHMRC Senior Principal Research Fellowship 1,059,660.

Compliance with ethical standards

Conflict of interest

The authors declare that over the past three years, Brian Harvey has participated in advisory boards and received honoraria from Servier®, and has received research funding from Servier® and Lundbeck®. The authors declare that, except for income from the primary employer and research funding to BHH from the above-mentioned organizations and agencies, no financial support or compensation has been received from any individual or corporate entity over the past three years for research or professional services, and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.


  1. Abildgaard A, Solskov L, Volke V, Harvey BH, Lund S, Wegener G (2011) A high-fat diet exacerbates depressive-like behavior in the flinders sensitive line (FSL) rat, a genetic model of depression. Psychoneuroendocrinology 36:623–633CrossRefPubMedGoogle Scholar
  2. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders (DSM-5®), 5th edn. American Psychiatric Publishing, Washington, DCCrossRefGoogle Scholar
  3. Antunes M, Biala G (2012) The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn Process 13:93–110CrossRefPubMedGoogle Scholar
  4. Ashton M, Berk M, Ng C, Hopwood M, Harvey B, Dean O (2016) The efficacy of adjunctive Garcinia Mangostana Linn pericarp for bipolar depression: a 24-week double-blind, randomised, placebo controlled trial. Bipolar Disord 18:168–168Google Scholar
  5. Austin MP, Mitchell P, Goodwin GM (2001) Cognitive deficits in depression: possible implications for functional neuropathology. Brit J sychiatry 178:200–206CrossRefGoogle Scholar
  6. Baldessarini RJ (2006) Drug therapy of depression and anxiety disorders. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. Edited by Brunton LL, Lazo JS, Parker KL. 429–460Google Scholar
  7. Berk M, Dean OM, Cotton SM, Jeavons S, Tanious M, Kohlmann K, Hewitt K, Moss K, Allwang C, Schapkaitz I, Robbins J, Cobb H, Ng F, Dodd S, Bush AI, Malhi GS (2014) The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial. J clin psychiatry 75:628–636CrossRefPubMedGoogle Scholar
  8. Boyce PM, Berk M (2016) Biological models of mental illness: implications for therapy development. Med J Aust 204:339–340CrossRefPubMedGoogle Scholar
  9. Brand SJ, Harvey BH (2017a) Exploring a post-traumatic stress disorder paradigm in flinders sensitive line rats to model treatment-resistant depression I: bio-behavioural validation and response to imipramine. Acta Neuropsychiatr 29:193–206CrossRefPubMedGoogle Scholar
  10. Brand SJ, Harvey BH (2017b) Exploring a post-traumatic stress disorder paradigm in flinders sensitive line rats to model treatment-resistant depression II: response to antidepressant augmentation strategies. Acta Neuropsychiatr 29:207–221CrossRefPubMedGoogle Scholar
  11. Brand S, Möller M, H Harvey B (2015) A review of biomarkers in mood and psychotic disorders: a dissection of clinical vs. preclinical correlates. Curr Neuropharmacol 13:324–368CrossRefPubMedPubMedCentralGoogle Scholar
  12. Broadbent NJ, Gaskin S, Squire LR, Clark RE (2009) Object recognition memory and the rodent hippocampus. Learning & memory (Cold Spring Harbor, NY) 17:5–11CrossRefGoogle Scholar
  13. Brocardo PS, Boehme F, Patten A, Cox A, Gil-Mohapel J, Christie BR (2012) Anxiety-and depression-like behaviors are accompanied by an increase in oxidative stress in a rat model of fetal alcohol spectrum disorders: protective effects of voluntary physical exercise. Neuropharmacology 62:1607–1618CrossRefPubMedGoogle Scholar
  14. Catorce MN, Gevorkian G (2016) LPS-induced murine Neuroinflammation model: main features and suitability for pre-clinical assessment of Nutraceuticals. Curr Neuropharmacol 14:155–164CrossRefPubMedPubMedCentralGoogle Scholar
  15. Chaivisuthangkura A, Malaikaew Y, Chaovanalikit A, Jaratrungtawee A, Panseeta P, Ratananukul P, Suksamrarn S (2009) Prenylated xanthone composition of garcinia mangostana (mangosteen) fruit hull. Chromatographia 69:315–318CrossRefGoogle Scholar
  16. Chen F, Wegener G, Madsen TM, Nyengaard JR (2013) Mitochondrial plasticity of the hippocampus in a genetic rat model of depression after antidepressant treatment. Synapse 67:127–134CrossRefPubMedGoogle Scholar
  17. Chenu F, El Mansari M, Blier P (2013). Electrophysiological effects of repeated administration of agomelatine on the dopamine, norepinephrine, and serotonin systems in the rat brain. Neuropsychopharmacology 38:275–284Google Scholar
  18. Chin Y-W, Kinghorn AD (2008) Structural characterization, biological effects, and synthetic studies on xanthones from mangosteen (Garcinia Mangostana), a popular botanical dietary supplement. Mini Rev Org Chem 5:355–364CrossRefPubMedPubMedCentralGoogle Scholar
  19. Chiu K, Lau WM, Lau HT, So KF, Chang RCC (2007) Micro-dissection of rat brain for RNA or protein extraction from specific brain region. JoVE 7:e269–e269Google Scholar
  20. Colalto C (2010) Herbal interactions on absorption of drugs: mechanisms of action and clinical risk assessment. Pharmacol Res 62:207–227CrossRefPubMedGoogle Scholar
  21. Conradi HJ, Ormel J, de Jonge P (2011) Presence of individual (residual). Symptoms during depressive episodes and periods of remission: a 3-year prospective study. Psychol Med 41:1165–1174CrossRefPubMedGoogle Scholar
  22. Coyle JT, Puttfarcken P (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science (New York, NY) 2621:689–695CrossRefGoogle Scholar
  23. Cryan JF, Valentino RJ, Lucki I (2005) Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neurosci Biobehav Rev 29:547–569CrossRefPubMedGoogle Scholar
  24. Dazzi L, Ladu S, Spiga F, Vacca G, Rivano A, Pira L, Biggio G (2002) Chronic treatment with imipramine or mirtazapine antagonizes stress- and FG7142-induced increase in cortical norepinephrine output in freely moving rats. Synapse 43:70–77CrossRefPubMedGoogle Scholar
  25. De Bundel D, Femenia T, DuPont CM, Konradsson-Geuken A, Feltmann K, Schilstrom B, Lindskog M (2013) Hippocampal and prefrontal dopamine D1/5 receptor involvement in the memory-enhancing effect of reboxetine. Int J Neuropsychopharmacol 16:2041–2051CrossRefPubMedGoogle Scholar
  26. Devi Sampath P, Vijayaraghavan K (2007) Cardioprotective effect of α-mangostin, a xanthone derivative from mangosteen on tissue defense system against isoproterenol-induced myocardial infarction in rats. J Biochem Mol Toxicol 21:336–339CrossRefPubMedGoogle Scholar
  27. Dey A, De JN (2015) Neuroprotective therapeutics from botanicals and phytochemicals against Huntington's disease and related neurodegenerative disorders. J Herb Med 5:1–19CrossRefGoogle Scholar
  28. Dodd S, Maes M, Anderson G, Dean OM, Moylan S, Berk M (2013) Putative neuroprotective agents in neuropsychiatric disorders. Prog Neuro-Psychopharmacol Biol Psychiatry 42:135–145CrossRefGoogle Scholar
  29. Du Jardin KG, Liebenberg N, Müller HK, Elfving B, Sanchez C, Wegener G (2016) Differential interaction with the serotonin system by S-ketamine, vortioxetine, and fluoxetine in a genetic rat model of depression Psychopharmacology (Berl) 233(14):2813–2825.Google Scholar
  30. Ennaceur A, Delacour J (1988) A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data. Behav Brain Res 31:47–59CrossRefPubMedGoogle Scholar
  31. Fajemiroye JO, da Silva DM, de Oliveira DR, Costa EA (2016) Treatment of anxiety and depression: medicinal plants in retrospect. Fundam Clin Pharmacol 30:198–215CrossRefPubMedGoogle Scholar
  32. Ferguson JN, Young LJ, Insel TR (2002) The neuroendocrine basis of social recognition. Front Neuroendocrinol 23:200–224CrossRefPubMedGoogle Scholar
  33. Ferreira F, Biojone C, Joca S, Guimaraes F (2008) Antidepressant-like effects of N-acetyl-L-cysteine in rats. Behav Pharmacol 19:747–757CrossRefPubMedGoogle Scholar
  34. Fukui K, OMOI N, Hayasaka T, Shinnkai T, Suzuki S, Abe K, Urano S (2002) Cognitive impairment of rats caused by oxidative stress and aging, and its prevention by vitamin E. Ann N Y Acad Sci 959:275–284CrossRefPubMedGoogle Scholar
  35. Garrity AR, Morton GA, Morten JC (2004) Nutraceutical mangosteen composition. 6730333 B1 20040504. US Patent. 7Google Scholar
  36. Gemmel M, Rayen I, Lotus T, van Donkelaar E, Steinbusch HW, De Lacalle S, Kokras N, Dalla C, Pawluski JL (2016). Developmental fluoxetine and prenatal stress effects on serotonin, dopamine, and synaptophysin density in the PFC and hippocampus of offspring at weaning. Dev Psychobiol 58:315–327Google Scholar
  37. Gigliucci V, Gormley S, Gibney S, Rouine J, Kerskens C, Connor TJ, Harkin A (2014) Characterisation of the antidepressant properties of nitric oxide synthase inhibitors in the olfactory bulbectomised rat model of depression. Eur Neuropsychopharmacol 24:1349–1361CrossRefPubMedGoogle Scholar
  38. Gillman P (2007) Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Brit Aust J Pharm 151:737–748CrossRefGoogle Scholar
  39. Gómez-Galán M, De Bundel D, Van Eeckhaut A, Smolders I, Lindskog M (2013) Dysfunctional astrocytic regulation of glutamate transmission in a rat model of depression. Mol Psychiatry 18:582–594CrossRefPubMedGoogle Scholar
  40. Gotlib IH, Joormann J (2010) Cognition and depression: current status and future directions. Ann Rev Clin Psychology 6:285–312CrossRefGoogle Scholar
  41. Grayson B, Idris NF, Neill JC (2007) Atypical antipsychotics attenuate a sub-chronic PCP-induced cognitive deficit in the novel object recognition task in the rat. Behav Brain Res 184:31–38CrossRefPubMedGoogle Scholar
  42. Gualtieri CT, Johnson LG, Benedict KB (2006) Neurocognition in depression: patients on and off medication versus healthy comparison subjects. J Neuropsychiatr Clin Neurosci 18:217–225CrossRefGoogle Scholar
  43. Han X, Tong J, Zhang J, Farahvar A, Wang E, Yang J, Samadani U, Smith DH, Huang JH (2011) Imipramine treatment improves cognitive outcome associated with enhanced hippocampal neurogenesis after traumatic brain injury in mice. J Neurotrauma 28:995–1007CrossRefPubMedPubMedCentralGoogle Scholar
  44. Harvey BH, Brand L, Jeeva Z, Stein DJ (2006) Cortical/hippocampal monoamines, HPA-axis changes and aversive behavior following stress and restress in an animal model of post-traumatic stress disorder. Physiol Behav 87(5):881–890CrossRefPubMedGoogle Scholar
  45. Harvey BH, Duvenhage I, Viljoen F, Scheepers N, Malan SF, Wegener G, Brink CB, Petzer JP (2010) Role of monoamine oxidase, nitric oxide synthase and regional brain monoamines in the antidepressant-like effects of methylene blue and selected structural analogues. Biochem Pharmacol 80:1580–1591CrossRefPubMedGoogle Scholar
  46. Hasegawa S, Nishi K, Watanabe A, Overstreet DH, Diksic M (2006) Brain 5-HT synthesis in the flinders sensitive line rat model of depression: an autoradiographic study. Neurochem Int 48:358–366CrossRefPubMedGoogle Scholar
  47. Hasler G (2010) Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World Psychiatry 9:155–161CrossRefPubMedPubMedCentralGoogle Scholar
  48. Jung HA, BN S, Keller WJ, Mehta RG, Kinghorn AD (2006) Antioxidant xanthones from the pericarp of Garcinia Mangostana (Mangosteen). J Agric Food Chem 54:2077–2082CrossRefPubMedGoogle Scholar
  49. Kessler RC, Bromet EJ (2013) The epidemiology of depression across cultures. Ann rev. Public Health 34:119–138CrossRefGoogle Scholar
  50. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 8:e1000412Google Scholar
  51. Köhler O, Benros ME, Nordentoft M, Farkouh ME, Iyengar RL, Mors O, Krogh J (2014) Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry 71:1381–1391CrossRefPubMedGoogle Scholar
  52. Lavi-Avnon Y, Yadid G, Overstreet DH, Weller A (2005) Abnormal patterns of maternal behavior in a genetic animal model of depression. Physiol Behav 84:607–615CrossRefPubMedGoogle Scholar
  53. Leonard B, Maes M (2012) Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev 36:764–785CrossRefPubMedGoogle Scholar
  54. Li L, Han AR, Kinghorn AD, Frye RF, Derendorf H, Butterweck V (2013) Pharmacokinetic properties of pure xanthones in comparison to a mangosteen fruit extract in rats. Planta Med 79:646–653CrossRefPubMedGoogle Scholar
  55. Liang YZ, Xie P, Chan K (2004) Quality control of herbal medicines. J Chromatogr B 812:53–70CrossRefGoogle Scholar
  56. Liebenberg N, Harvey BH, Brand L, Brink CB (2010) Antidepressant-like properties of phosphodiesterase type 5 inhibitors and cholinergic dependency in a genetic rat model of depression. Behav Pharmacol 21:540–547CrossRefPubMedGoogle Scholar
  57. Lucki I (1997) The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav Pharmacol 8:523–532CrossRefPubMedGoogle Scholar
  58. Maes M, Galecki P, Chang YS, Berk M (2011) A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro) degenerative processes in that illness. Prog Neuro-Psychopharmacol Biol Psychiatry 35:676–692CrossRefGoogle Scholar
  59. Majumder I, White JM, Irvine RJ (2011) Antidepressant-like effects of 3,4-methylenedioxymethamphetamine in an animal model of depression. Behav Pharmacol 22:758–765CrossRefPubMedGoogle Scholar
  60. Márquez L, García-Bueno B, Madrigal JL, Leza JC (2012) Mangiferin decreases inflammation and oxidative damage in rat brain after stress. Eur. J Nutr 51:729–739Google Scholar
  61. Márquez-Valadez B, Lugo-Huitrón R, Valdivia-Cerda V, Miranda-Ramírez LR, Pérez-De La Cruz V, González-Cuahutencos O, Rivero-Cruz I, Mata R, Santamaría A, Pedraza-Chaverrí J (2009) The natural xanthone alpha-mangostin reduces oxidative damage in rat brain tissue. Nutr Neurosci 12:35–42CrossRefPubMedGoogle Scholar
  62. McIntyre RS, Cha DS, Soczynska JK, Woldeyohannes HO, Gallaugher LA, Kudlow P, Alsuwaidan M, Baskaran A (2013) Cognitive deficits and functional outcomes in major depressive disorder: determinants, substrates, and treatment interventions. Depress Anxiety 30:515–527CrossRefPubMedGoogle Scholar
  63. Mehlman PT, Westergaard GC, Hoos BJ (2000) CSF 5-HIAA and nighttime activity in free-ranging primates. Neuropsychopharmacology 22:210–218CrossRefPubMedGoogle Scholar
  64. Mokoena ML, Harvey BH, Viljoen F, Ellis SM, Brink CB (2015) Ozone exposure of flinders sensitive line rats is a rodent translational model of neurobiological oxidative stress with relevance for depression and antidepressant response. Psychopharmacology (Berlin) 232:2921–2938CrossRefGoogle Scholar
  65. Möller M, Harvey BH, Du Preez JL, Emsley R (2011) Isolation rearing-induced deficits in sensorimotor gating and social interaction in rats are related to cortico-striatal oxidative stress, and reversed by sub-chronic clozapine administration. Eur Neuropsychopharmacol 21:471–483CrossRefPubMedGoogle Scholar
  66. Möller M, Du Preez JL, Viljoen FP, Berk M, Emsley R, Harvey BH (2013) Social isolation rearing induces mitochondrial, immunological, neurochemical and behavioural deficits in rats, and is reversed by clozapine or N-acetyl cysteine. Brain Behav Immun 30:156–167CrossRefPubMedGoogle Scholar
  67. Morley-Fletcher S, Darnaudery M, Mocaer E, Froger N, Lanfumey L, Laviola G, Casolini P, Zuena A, Marzano L, Hamon M (2004) Chronic treatment with imipramine reverses immobility behaviour, hippocampal corticosteroid receptors and cortical 5-HT 1A receptor mRNA in prenatally stressed rats. Neuropharmacology 47:841–847CrossRefPubMedGoogle Scholar
  68. Negi J, Bisht V, Singh P, Rawat M, Joshi G (2013) Naturally occurring Xanthones: chemistry and biology. J Appl Chem 2013:1Google Scholar
  69. Neumann I, Wegener G, Homberg J, Cohen H, Slattery D, Zohar J, Olivier J, Mathe A (2011) Animal models of depression and anxiety: what do they tell us about human condition? Prog Neuro-Psychopharmacol Biol Psychiatry 35:1357–1375CrossRefGoogle Scholar
  70. Overstreet DH, Wegener G (2013) The flinders sensitive line rat model of depression--25 years and still producing. Pharmacol Rev 65:143–155CrossRefPubMedGoogle Scholar
  71. Overstreet DH, Friedman E, Mathé AA, Yadid G (2005) The flinders sensitive line rat: a selectively bred putative animal model of depression. Neurosci Biobehav Rev 29(4–5):739–759CrossRefPubMedGoogle Scholar
  72. Pardo Andreu GL, Maurmann N, Reolon GK, de Farias CB, Schwartsmann G, Delgado R, Roesler R (2010) Mangiferin, a naturally occurring glucoxilxanthone improves long-term object recognition memory in rats. Eur J Pharmacol 635:124–128CrossRefPubMedGoogle Scholar
  73. Pedraza-Chaverri J, Cárdenas-Rodríguez N, Orozco-Ibarra M, Pérez-Rojas JM (2008) Medicinal properties of mangosteen (Garcinia Mangostana). Food Chem Toxicol 46:3227–3239CrossRefPubMedGoogle Scholar
  74. Peselow ED, Corwin J, Fieve RR, Rotrosen J, Cooper TB (1991) Disappearance of memory deficits in outpatient depressives responding to imipramine. J Affect Disord 21:173–183CrossRefPubMedGoogle Scholar
  75. Phyu MP, Tangpong J (2014) Neuroprotective effects of xanthone derivative of Garcinia Mangostana against lead-induced acetylcholinesterase dysfunction and cognitive impairment. Food Chem Toxicol 70:151CrossRefPubMedGoogle Scholar
  76. Pineyro G, Blier P (1999) Autoregulation of serotonin neurons: role in antidepressant drug action. Pharmacol Rev 51:533–591PubMedGoogle Scholar
  77. Porsolt RD (2000) Animal models of depression: utility for transgenic research. Rev Neurosci 11:53–58CrossRefPubMedGoogle Scholar
  78. Reus GZ, Stringari RB, de Souza B, Petronilho F, Dal-Pizzol F, Hallak JE, Zuardi AW, Crippa JA, Quevedo J (2010) Harmine and imipramine promote antioxidant activities in prefrontal cortex and hippocampus. Oxidative Med Cell Longev 3:325–331CrossRefGoogle Scholar
  79. Richards D (2011) Prevalence and clinical course of depression: a review. Clin Psychol Rev 31:1117–1125CrossRefPubMedGoogle Scholar
  80. Rojas P, Serrano-García N, Medina-Campos ON, Pedraza-Chaverri J, Ögren SO, Rojas C (2011) Antidepressant-like effect of a Ginkgo Biloba extract (EGb761) in the mouse forced swimming test: role of oxidative stress. Neurochem Int 59:628–636CrossRefPubMedGoogle Scholar
  81. Sani MH, Taher M, Susanti D, Kek TL, Salleh MZ, Zakaria ZA (2015) Mechanisms of α-mangostin-induced antinociception in a rodent model. Biol Res Nurs 17:68–77CrossRefPubMedGoogle Scholar
  82. Sarandol A, Sarandol E, Eker SS, Erdinc S, Vatansever E, Kirli S (2007) Major depressive disorder is accompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative–antioxidative systems. Hum Psychopharmacol Clin Exp 22:67–73CrossRefGoogle Scholar
  83. Shannon NJ, Gunnet JW, Moore KE (1986) A comparison of biochemical indices of 5-hydroxytryptaminergic neuronal activity following electrical stimulation of the dorsal raphe nucleus. J Neurochem 47:958–965CrossRefPubMedGoogle Scholar
  84. Slattery DA, Cryan JF (2012) Using the rat forced swim test to assess antidepressant-like activity in rodents. Nat Protoc 7:1009–1014CrossRefPubMedGoogle Scholar
  85. Talbott SM, Morton DA, Templeman JF (2011) Mangosteen–traditional and modern uses. J Austr Integrative Med Ass 16(1):10–11Google Scholar
  86. Toua C, Brand L, Möller M, Harvey BH, Emsley RA (2010) The effects of sub-chronic clozapine and haloperidol administration on isolation rearing induced changes in frontal cortical N-methyl-d-aspartate and D1 receptor binding in rats. Neuroscience 165:492–499CrossRefPubMedGoogle Scholar
  87. Udani JK, Singh BB, Barratt ML, Singh VJ (2009) Evaluation of mangosteen juice blend on biomarkers of inflammation in obese subjects: a pilot, dose finding study. Nutr J 8:1CrossRefGoogle Scholar
  88. Uher R, Payne JL, Pavlova B, Perlis RH (2014) Major depressive disorder in DSM-5: implications for clinical practice and research of changes from DSM-IV. Depression. Anxiety 31:459–471CrossRefPubMedGoogle Scholar
  89. Uys M, Shahid M, Sallinen J, Harvey BH (2017) The α2C-adrenoceptor antagonist, ORM-10921, exerts antidepressant-like effects in the flinders sensitive line rat. Behav. Pharmacology 28:9–18Google Scholar
  90. Walker EB (2007) HPLC analysis of selected xanthones in mangosteen fruit. J Sep Sci 30:1229–1234CrossRefPubMedGoogle Scholar
  91. Zhang M, He L, Wan C, Zhao Z (2010) A meta-analysis of oxidative stress markers in schizophrenia. Sci China Life Sci 53:112–124CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Inge Oberholzer
    • 1
  • Marisa Möller
    • 1
  • Brendan Holland
    • 2
  • Olivia M. Dean
    • 3
    • 4
    • 5
  • Michael Berk
    • 3
    • 6
  • Brian H. Harvey
    • 1
  1. 1.Division of Pharmacology and Center of Excellence for Pharmaceutical Sciences, School of PharmacyNorth West UniversityPotchefstroomSouth Africa
  2. 2.Centre for Chemistry and Biotechnology, School of Life and Environmental SciencesDeakin UniversityGeelongAustralia
  3. 3.Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon HealthGeelongAustralia
  4. 4.Florey Institute for Neuroscience and Mental HealthUniversity of MelbourneParkvilleAustralia
  5. 5.Department of Psychiatry, Level 1 North, Main Block, Royal Melbourne HospitalUniversity of MelbourneParkvilleAustralia
  6. 6.Orygen, The National Centre of Excellence in Youth Mental Health, the Department of Psychiatry, and the Florey Institute of Neuroscience and Mental HealthThe University of MelbourneParkvilleAustralia

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