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Animal model of menopausal depressive-like state in female mice: prolongation of immobility time in the forced swimming test following ovariectomy

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Abstract

Rationale

The onset of menopause produces a depressive state in women, but the mechanism involved in menopause-induced depression is poorly understood.

Objectives

Building upon previous studies that used the duration of immobility in male rodents during the forced swimming test as a behavioral measure of the depression-like state, we investigated whether the duration of immobility in female mice was altered following bilateral ovariectomy. We also evaluated the chronic effects of estradiol, antidepressants, scopolamine, and diazepam on both the duration of immobility and uterine weight.

Methods

We bilaterally resected the ovaries of ICR albino female mice at 9 weeks of age. The day after the surgery, drug treatment was started once per day for 2 weeks, after which, the behavioral test was administered. The duration of immobility was measured during the last 4 min of the 6-min trial.

Results

Bilateral ovariectomy significantly increased the duration of immobility. Chronic treatment with estradiol (15–30 μg kg−1 day−1) prevented the prolongation of immobility following ovariectomy and produced a significant increase in uterine weight. Chronic treatment with imipramine, fluvoxamine, and milnacipran at 5, 10, and 15 mg kg−1 day−1, respectively, significantly reduced the duration of immobility, whereas treatment with scopolamine or diazepam (0.5, 1.0, and 2.0 mg kg−1 day−1 for both) was ineffective.

Conclusion

Based on these results, we suggest that the prolongation of immobility in female mice following ovariectomy may be a useful tool for investigating menopausal depression.

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References

  • Alonso SJ, Castellano MA, Afonso D, Rodriguez M (1991) Sex differences in behavioral despair: relationships between behavioral despair and open field activity. Physiol Behav 49:69–72

    Article  PubMed  CAS  Google Scholar 

  • Bernardi M, Vergoni AV, Sandrini M, Tagliavini S, Bertolini A (1989) Influence of ovariectomy, estradiol and progesterone on the behavior of mice in an experimental model of depression. Physiol Behav 45:1067–1068

    Article  PubMed  CAS  Google Scholar 

  • Baker VL, Leitman D, Jaffe RB (2000) Selective estrogen receptor modulators in reproductive medicine and biology. Obstet Gynecol Surv 55:s21–s47

    Article  PubMed  CAS  Google Scholar 

  • Barros HM, Ferigolo M (1998) Ethopharmacology of imipramine in the forced swimming test: gender differences. Neurosci Biobehav Rev 23:279–286

    Article  PubMed  CAS  Google Scholar 

  • Bhavnani BR, Strickler RC (2005) Menopausal hormone therapy. J Obstet Gynaecol Can 27:137–162

    PubMed  Google Scholar 

  • Biala G (1998) Antidepressant-like properties of some serotonin receptor ligands and calcium channel antagonists measured with the forced swimming test in mice. Pol J Pharmacol 50:117–124

    PubMed  CAS  Google Scholar 

  • Birkhauser M (2002) Depression, menopause and estrogens: is there a correlation? Maturitas 15(Suppl 1):S3–S8

    Article  Google Scholar 

  • Borsini F, Meli A (1988) Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology (Berl) 94:147–160

    Article  CAS  Google Scholar 

  • Bourin M, Colombel MC, Malinge M, Bradwejn J (1991) Clonidine as a sensitizing agent in the forced swimming test for revealing antidepressant activity. J Psychiatry Neurosci 16:199–203

    PubMed  CAS  Google Scholar 

  • Brotto LA, Barr AM, Gorzalka BB (2000) Sex differences in forced-swim and open-field test behaviours after chronic administration of melatonin. Eur J Pharmacol 402(1–2):87–93

    Article  PubMed  CAS  Google Scholar 

  • Cryan JF, Hoyer D, Markou A (2003) Withdrawal from chronic amphetamine induces depressive-like behavioral effects in rodents. Biol Psychiatry 54:49–58

    Article  PubMed  CAS  Google Scholar 

  • De Pablo JM, Ortiz-Caro J, Sanchez-Santed F, Guillamon A (1991) Effect of diazepam, pentobarbital, scopolamine and the timing of saline injection on learned immobility in rats. Physiol Behav 50:895–899

    Article  PubMed  Google Scholar 

  • Drossopoulou G, Antoniou K, Kitraki E, Papathanasiou G, Papalexi E, Dalla C, Papadopoulou-Daifoti Z (2004) Sex differences in behavioral, neurochemical and neuroendocrine effects induced by the forced swim test in rats. Neuroscience 126:849–857

    Article  PubMed  CAS  Google Scholar 

  • Estrada-Camarena E, Fernandez-Guasti A, Lopez-Rubalcava C (2003) Antidepressant-like effect of different estrogenic compounds in the forced swimming test. Neuropsychopharmacology 28:830–838

    PubMed  CAS  Google Scholar 

  • Fink G, Sumner BE (1996) Oestrogen and mental state. Nature 383:306

    Article  PubMed  CAS  Google Scholar 

  • Fink G, Sumner BE, Rosie R, Grace O, Quinn JP (1996) Estrogen control of central neurotransmission: effect on mood, mental state, and memory. Cell Mol Neurobiol 16:325–344

    Article  PubMed  CAS  Google Scholar 

  • Fink G, Sumner BE, McQueen JK, Wilson H, Rosie R (1998) Sex steroid control of mood, mental state and memory. Clin Exp Pharmacol Physiol 25:764–775

    Article  PubMed  CAS  Google Scholar 

  • Galea L, Wide J, Barr A (2001) Estradiol alleviates depressive-like symptoms in a novel animal model of post-partum depression. Behav Brain Res 122:1–9

    Article  PubMed  CAS  Google Scholar 

  • Hata T, Nishikawa H, Itoh E, Watanabe A (1999) Depressive state with anxiety in repeated cold-stressed mice in forced swimming tests. Jpn J Pharmacol 79:243–249

    Article  PubMed  CAS  Google Scholar 

  • Hilakivi-Clarke L (1996) Role of estradiol in alcohol intake and alcohol-related behaviors. J Stud Alcohol 57:162–170

    PubMed  CAS  Google Scholar 

  • Kawashima K, Araki H, Aihara H (1986) Effect of chronic administration of antidepressants on duration of immobility in rats forced to swim. Jpn J Pharmacol 40:199–204

    Article  PubMed  CAS  Google Scholar 

  • Kimura N, Yoshimura H, Ogawa N (1987) Sex differences in stress-induced gastric ulceration: effects of castration and ovariectomy. Psychobiology 15:175–178

    Google Scholar 

  • Landry M, Di Paolo T (2003) Effect of chronic estradiol, tamoxifen or raloxifene treatment on serotonin 5-HT1A receptor. Mol Brain Res 112:82–89

    Article  PubMed  CAS  Google Scholar 

  • Okada M, Hayashi N, Kometani M, Nakao K, Inukai T (1997) Influences of ovariectomy and continuous replacement of 17β-estradiol on the tail skin temperature and behavior in the forced swimming test in rats. Jpn J Pharmacol 73:93–96

    Article  PubMed  CAS  Google Scholar 

  • Payne JL (2003) The role of estrogen in mood disorders in women. Int Rev Psychiatry 15:280–290

    Article  PubMed  CAS  Google Scholar 

  • Pearlstein T, Rosen K, Stone AB (1997) Mood disorders and menopause. Endocrinol Metab Clin North Am 26:279–294

    Article  PubMed  CAS  Google Scholar 

  • Petit-Demouliere B, Chenu F, Bourin M (2005) Forced swimming test in mice: a review of antidepressant activity. Psychopharmacology (Berl) 177:245–255

    Article  CAS  Google Scholar 

  • Porsolt RD, Bertin A, Jalfre M (1977) Behavioural despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn 229:327–336

    PubMed  CAS  Google Scholar 

  • Porsolt RD, Bertin A, Jalfre M (1978) “Behavioural despair” in rats and mice: strain differences and the effects of imipramine. Eur J Pharmacol 51:291–294

    Article  PubMed  CAS  Google Scholar 

  • Rachman IM, Unnerstall JR, Pfaff DW, Cohen RS (1998) Estrogen alters behavior and forebrain c-fos expression in ovariectomized rats subjected to the forced swim test. Proc Natl Acad Sci U S A 95:13941–13946

    Article  PubMed  CAS  Google Scholar 

  • Rocha BA, Fleischer R, Schaeffer JM, Rohrer SP, Hickey GJ (2005) 17β-estradiol-induced antidepressant-like effect in the forced swim test is absent in estrogen receptor-beta knockout (BERKO) mice. Psychopharmacology (Berl) 179:637–643

    Article  CAS  Google Scholar 

  • Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women's Health Initiative Investigators (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women's health initiative randomized controlled trial. JAMA 288:321–333

    Article  PubMed  CAS  Google Scholar 

  • Steiner M, Dunn E, Born L (2003) Hormones and mood: from menarche to menopause and beyond. J Affect Disord 74:67–83

    Article  PubMed  CAS  Google Scholar 

  • Sugiura K, Yoshimura Y, Yokoyama H (1997) An animal model of copulatory disorder induced by social stress in male mice: effects of apomorphine and l-dopa. Psychopharmacology (Berl) 133:249–255

    Article  CAS  Google Scholar 

  • Taylor M (2001) Psychological consequences of surgical menopause. J Reprod Med 46(Suppl 3):317–324

    PubMed  CAS  Google Scholar 

  • Tsourounis C (2001) Clinical effects of phytoestrogens. Clin Obstet Gynecol 44:836–842

    Article  PubMed  CAS  Google Scholar 

  • Willner P, Mitchell PJ (2002) The validity of animal models of predisposition to depression. Behav Pharmacol 13:169–188

    PubMed  CAS  Google Scholar 

  • Yonkers KA (2003) Special issues related to the treatment of depression in women. J Clin Psychiatry 18:8–13

    Google Scholar 

  • Yoshimura H (1987) Studies contrasting drug effects on reproduction induced agonistic behaviour in male and female mice. In: Olivier B, Mos J, Brain PF (eds) Ethopharmacology of agonistic behaviour in animals and humans. Martinus Nijhoff, Dordrecht, pp 94–109

    Google Scholar 

Download references

Acknowledgements

The following companies generously donated pharmaceutical reagents used in this study: Sumitomo Pharmaceutical Co., Ltd. (diazepam), Solvay-Meiji Yakuhin K.K. (fluvoxamine), and Asahi Kasei Corporation (milnacipran).

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Authors and Affiliations

  1. Behavioral Pharmacology Laboratory, Faculty of Health Sciences, Ehime University School of Medicine, Toon City, Ehime, 791-0295, Japan

    Naoko Bekku & Hiroyuki Yoshimura

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  1. Naoko Bekku
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  2. Hiroyuki Yoshimura
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Correspondence to Hiroyuki Yoshimura.

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Bekku, N., Yoshimura, H. Animal model of menopausal depressive-like state in female mice: prolongation of immobility time in the forced swimming test following ovariectomy. Psychopharmacology 183, 300–307 (2005). https://doi.org/10.1007/s00213-005-0179-0

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  • DOI: https://doi.org/10.1007/s00213-005-0179-0

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