Skip to main content
SpringerLink
Log in

The Effect of 17β-Estradiol and Its Analogues on Cognition in Preclinical and Clinical Research: Relevance to Schizophrenia

  • Chapter
  • First Online:
Psychiatry and Neuroscience Update - Vol. II

Abstract

Epidemiological and clinical evidence suggests estrogen plays a role in the development and severity of schizophrenia, and a growing body of literature indicates estrogen therapy is a feasible treatment option. Current pharmacological treatments for schizophrenia primarily address the positive symptoms and fail to adequately address the cognitive deficits; thus, novel treatments require exploration. The sex steroid hormone 17β-estradiol has been extensively studied as a treatment for schizophrenia, and selective estrogen receptor modulators (SERMs) have been more recently investigated as other potential candidates. This chapter aims to critically analyse the current evidence for the clinical applicability of 17β-estradiol and the SERM raloxifene for the treatment of schizophrenia, with particular emphasis on treating cognitive symptoms.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Gogos A, van den Buuse M. Comparing the effects of 17β-oestradiol and the selective oestrogen receptor modulators, raloxifene and tamoxifen, on prepulse inhibition in female rats. Schizophr Res. 2015;168(3):634–9.

    Article  PubMed  Google Scholar 

  2. Kulkarni J, Berk M, Gavrilidis E, Fitzgerald P, Wang W, Worsley R, et al. Estradiol for treatment-resistant schizophrenia: a large-scale randomized–controlled trial in women of child-bearing age. Mol Psychiatry. 2015;20(6):695–702.

    Article  CAS  PubMed  Google Scholar 

  3. Riecher-Rössler A. Estrogens and schizophrenia. In: Bergemann N, Riecher-Rössler PDA, editors. Estrogen effects in psychiatric disorders. Vienna: Springer; 2005.

    Google Scholar 

  4. Saha S, Chant D, Welham J, McGrath J. A systematic review of the prevalence of schizophrenia. PLoS Med. 2005;2(5):e141.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Mueser KT, McGurk SR. Schizophrenia. Lancet. 2004;363(9426):2063–72.

    Article  PubMed  Google Scholar 

  6. Bowie CR, Harvey PD. Cognitive deficits and functional outcome in schizophrenia. Neuropsychiatr Dis Treat. 2006;2(4):531–6.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996;153(3):321–30.

    Article  CAS  PubMed  Google Scholar 

  8. Marder SR. The NIMH-MATRICS project for developing cognition-enhancing agents for schizophrenia. Dialogues Clin Neurosci. 2006;8(1):109–13.

    PubMed  PubMed Central  Google Scholar 

  9. Keefe RSE, Silva SG, Perkins DO, Lieberman JA. The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis. Schizophr Bull. 1999;25(2):201–22.

    Article  CAS  PubMed  Google Scholar 

  10. Keefe RSE. The longitudinal course of cognitive impairment in schizophrenia: an examination of data from premorbid through posttreatment phases of illness. J Clin Psychiatry. 2014;75(Suppl 2):8–13.

    Article  PubMed  Google Scholar 

  11. Stevenson A. Oxford dictionary of english. Oxford: Oxford University Press; 2010.

    Google Scholar 

  12. Forbes NF, Carrick LA, McIntosh AM, Lawrie SM. Working memory in schizophrenia: a meta-analysis. Psychol Med. 2009;39(6):889–905.

    Article  CAS  PubMed  Google Scholar 

  13. van Oel CJ, Sitskoorn MM, Cremer MPM, Kahn RS. School performance as a premorbid marker for schizophrenia: a twin study. Schizophr Bull. 2002;28(3):401–14.

    Article  PubMed  Google Scholar 

  14. Park S, Püschel J, Sauter BH, Rentsch M, Hell D. Spatial working memory deficits and clinical symptoms in schizophrenia: a 4-month follow-up study. Biol Psychiatry. 1999;46(3):392–400.

    Article  CAS  PubMed  Google Scholar 

  15. Marder SR, Fenton W. Measurement and treatment research to improve cognition in schizophrenia: NIMH MATRICS initiative to support the development of agents for improving cognition in schizophrenia. Schizophr Res. 2004;72(1):5–9.

    Article  PubMed  Google Scholar 

  16. Häfner H, Maurer K, Löffler W, Riecher-Rössler A. The influence of age and sex on the onset and early course of schizophrenia. Br J Psychiatry J Ment Sci. 1993;162:80–6.

    Article  Google Scholar 

  17. Abel KM, Drake R, Goldstein JM. Sex differences in schizophrenia. Int Rev Psychiatry. 2010;22(5):417–28.

    Article  PubMed  Google Scholar 

  18. Canuso CM, Pandina G. Gender and schizophrenia. Psychopharmacol Bull. 2007;40(4):178–90.

    PubMed  Google Scholar 

  19. Markham JA. Sex steroids and schizophrenia. Rev Endocr Metab Disord. 2012;13(3):187–207.

    Article  CAS  PubMed  Google Scholar 

  20. Brockington IF, Kelly A, Hall P, Deakin W. Premenstrual relapse of puerperal psychosis. J Affect Disord. 1988;14(3):287–92.

    Article  CAS  PubMed  Google Scholar 

  21. Kendell RE, Chalmers JC, Platz C. Epidemiology of puerperal psychoses. Br J Psychiatry. 1987;150(5):662–73.

    Article  CAS  PubMed  Google Scholar 

  22. Nott PN. Psychiatric illness following childbirth in Southampton: a case register study. Psychol Med. 1982;12(03):557–61.

    Article  CAS  PubMed  Google Scholar 

  23. Seeman M. Psychopathology in women and men: focus on female hormones. Am J Psychiatry. 1997;154(12):1641–7.

    Article  CAS  PubMed  Google Scholar 

  24. Dalton K. Menstruation and acute psychiatric illnesses. Br Med J. 1959;1(5115):148–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Halari R, Kumari V, Mehrotra R, Wheeler M, Hines M, Sharma T. The relationship of sex hormones and cortisol with cognitive functioning in schizophrenia. J Psychopharmacol (Oxf). 2004;18(3):366–74.

    Article  CAS  Google Scholar 

  26. Hallonquist JD, Seeman M, Lang M, Rector NA. Variation in symptom severity over the menstrual cycle of schizophrenics. Biol Psychiatry. 1993;33(3):207–9.

    Article  CAS  PubMed  Google Scholar 

  27. Cohen RZ, Seeman M, Gotowiec A, Kopala L. Earlier puberty as a predictor of later onset of schizophrenia in women. Am J Psychiatry. 1999;156(7):1059–64.

    CAS  PubMed  Google Scholar 

  28. Fischer B, Gleason C, Asthana S. Effects of hormone therapy on cognition and mood. Fertil Steril. 2014;101(4):898–904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Srivastava DP, Woolfrey KM, Penzes P. Insights into rapid modulation of neuroplasticity by brain estrogens. Pharmacol Rev. 2013;65(4):1318–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ross SM. Menstruation in its relationships to insanity. Br J Psychiatry. 1909;55(229):270–80.

    Article  Google Scholar 

  31. Lønning PE, Taylor PD, Anker G, Iddon J, Wie L, Jørgensen L-M, et al. High-dose estrogen treatment in postmenopausal breast cancer patients heavily exposed to endocrine therapy. Breast Cancer Res Treat. 2001;67(2):111–6.

    Article  PubMed  Google Scholar 

  32. Oh WK. The evolving role of estrogen therapy in prostate cancer. Clin Prostate Cancer. 2002;1(2):81–9.

    Article  CAS  PubMed  Google Scholar 

  33. Lindsay R, Tohme JF. Estrogen treatment of patients with established postmenopausal osteoporosis. Obstet Gynecol. 1990;76(2):290–5.

    CAS  PubMed  Google Scholar 

  34. Klaiber EL, Broverman DM, Vogel W, Kobayashi Y. Estrogen therapy for severe persistent depressions in women. Arch Gen Psychiatry. 1979;36(5):550–4.

    Article  CAS  PubMed  Google Scholar 

  35. Ahokas A, Kaukoranta J, Aito M. Estrogen deficiency in severe postpartum depression: successful treatment with sublingual physiologic 17beta-estradiol: a preliminary study. J Clin Psychiatry. 2001;62(5):332–6.

    Article  CAS  PubMed  Google Scholar 

  36. Schmidt PJ, Nieman L, Danaceau MA, Tobin MB, Roca CA, Murphy JH, et al. Estrogen replacement in perimenopause-related depression: a preliminary report. Am J Obstet Gynecol. 2000;183(2):414–20.

    Article  CAS  PubMed  Google Scholar 

  37. Kulkarni J, Garland KA, Scaffidi A, Headey B, Anderson R, de Castella A, et al. A pilot study of hormone modulation as a new treatment for mania in women with bipolar affective disorder. Psychoneuroendocrinology. 2006;31(4):543–7.

    Article  CAS  PubMed  Google Scholar 

  38. Rao ML, Kölsch H. Effects of estrogen on brain development and neuroprotection—implications for negative symptoms in schizophrenia. Psychoneuroendocrinology. 2003;28(Supplement 2):83–96.

    Article  CAS  PubMed  Google Scholar 

  39. Seeman M. The role of estrogen in schizophrenia. J Psychiatry Neurosci. 1996;21(2):123–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Diczfalusy E, Lauritzen C. Oestrogene beim Menschen. Berlin/Heidelberg: Springer; 1961.

    Book  Google Scholar 

  41. Bergemann N, Riecher-Rössler A. Estrogen effects in psychiatric disorders. New York: Springer; 2005.

    Book  Google Scholar 

  42. Montgomery J, Winterbottom E, Jessani M, Kohegyi E, Fulmer J, Seamonds B, et al. Prevalence of hyperprolactinemia in schizophrenia: association with typical and atypical antipsychotic treatment. J Clin Psychiatry. 2004;65(11):1491–8.

    Article  PubMed  Google Scholar 

  43. Bergemann N, Parzer P, Nagl I, Salbach B, Runnebaum B, Mundt C, et al. Acute psychiatric admission and menstrual cycle phase in women with schizophrenia. Arch Womens Ment Health. 2002;5(3):119–26.

    Article  CAS  PubMed  Google Scholar 

  44. Bergemann N, Mundt C, Parzer P, Jannakos I, Nagl I, Salbach B, et al. Plasma concentrations of estradiol in women suffering from schizophrenia treated with conventional versus atypical antipsychotics. Schizophr Res. 2005;73(2–3):357–66.

    Article  PubMed  Google Scholar 

  45. Zhang-Wong JH, Seeman MV. Antipsychotic drugs, menstrual regularity and osteoporosis risk. Arch Womens Ment Health. 2002;5(3):93–8.

    Article  CAS  PubMed  Google Scholar 

  46. Gogos A, Sbisa AM, Sun J, Gibbons A, Udawela M, Dean B. A role for estrogen in schizophrenia: clinical and preclinical findings. Int J Endocrinol. 2015;2015:615356.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Weickert CS, Miranda-Angulo AL, Wong J, Perlman WR, Ward SE, Radhakrishna V, et al. Variants in the estrogen receptor alpha gene and its mRNA contribute to risk for schizophrenia. Hum Mol Genet. 2008;17(15):2293–309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Sayed Y, Taxel P. The use of estrogen therapy in men. Curr Opin Pharmacol. 2003;3(6):650–4.

    Article  CAS  PubMed  Google Scholar 

  49. Azcoitia I, Yague JG, Garcia-Segura LM. Estradiol synthesis within the human brain. Neuroscience. 2011;191:139–47.

    Article  CAS  PubMed  Google Scholar 

  50. Broverman DM, Vogel W, Klaiber EL, Majcher D, Shea D, Paul V. Changes in cognitive task performance across the menstrual cycle. J Comp Physiol Psychol. 1981;95(4):646–54.

    Article  CAS  PubMed  Google Scholar 

  51. Sherwin BB. Estrogen and cognitive functioning in women. Endocr Rev. 2003;24(2):133–51.

    Article  CAS  PubMed  Google Scholar 

  52. Joffe H, Hall JE, Gruber S, Sarmiento IA, Cohen LS, Yurgelun-Todd D, et al. Estrogen therapy selectively enhances prefrontal cognitive processes: a randomized, double-blind, placebo-controlled study with functional magnetic resonance imaging in perimenopausal and recently postmenopausal women. Menopause. 2006;13(3):411–22.

    Article  PubMed  Google Scholar 

  53. Luine VN, Jacome L, Maclusky N. Rapid enhancement of visual and place memory by estrogens in rats. Endocrinology. 2003;144(7):2836–44.

    Article  CAS  PubMed  Google Scholar 

  54. Inagaki T, Gautreaux C, Luine VN. Acute estrogen treatment facilitates recognition memory consolidation and alters monoamine levels in memory-related brain areas. Horm Behav. 2010;58(3):415–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Barha CK, Galea LAM. Influence of different estrogens on neuroplasticity and cognition in the hippocampus. Biochim Biophys Acta. 2010;1800(10):1056–67.

    Article  CAS  PubMed  Google Scholar 

  56. Luine VN. Estradiol and cognitive function: past, present and future. Horm Behav. 2014;66(4):602–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Wharton W, Baker LD, Gleason CE, Dowling M, Barnet JH, Johnson S, et al. Short-term hormone therapy with transdermal estradiol improves cognition for postmenopausal women with Alzheimer’s disease: results of a randomized controlled trial. J Alzheimers Dis. 2011;26(3):495–505.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Sundström Poromaa I, Gingnell M. Menstrual cycle influence on cognitive function and emotion processing from a reproductive perspective. Front Neurosci. 2014;8:380.

    PubMed  PubMed Central  Google Scholar 

  59. Hausmann M, Slabbekoorn D, Van Goozen SHM, Cohen-Kettenis PT, Gunturkun O. Sex hormones affect spatial abilities during the menstrual cycle. Behav Neurosci. 2000;114(6):1245–50.

    Article  CAS  PubMed  Google Scholar 

  60. Sherwin BB. Estrogen and cognitive functioning in women: lessons we have learned. Behav Neurosci. 2012;126(1):123–7.

    Article  CAS  PubMed  Google Scholar 

  61. Hampson E. Variations in sex-related cognitive abilities across the menstrual cycle. Brain Cogn. 1990;14(1):26–43.

    Article  CAS  PubMed  Google Scholar 

  62. Gordon HW, Lee PA. No difference in cognitive performance between phases of the menstrual cycle. Psychoneuroendocrinology. 1993;18(7):521–31.

    Article  CAS  PubMed  Google Scholar 

  63. Jacobs E, D’Esposito M. Estrogen shapes dopamine-dependent cognitive processes: Implications for women’s health. J Neurosci. 2011;31(14):5286–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Maki PM, Rich JB, Rosenbaum SR. Implicit memory varies across the menstrual cycle: estrogen effects in young women. Neuropsychologia. 2002;40(5):518–29.

    Article  PubMed  Google Scholar 

  65. Mordecai KL, Rubin LH, Maki PM. Effects of menstrual cycle phase and oral contraceptive use on verbal memory. Horm Behav. 2008;54(2):286–93.

    Article  CAS  PubMed  Google Scholar 

  66. Rosenberg L, Park S. Verbal and spatial functions across the menstrual cycle in healthy young women. Psychoneuroendocrinology. 2002;27(7):835–41.

    Article  CAS  PubMed  Google Scholar 

  67. Gogos A. Natural and synthetic sex hormones: effects on higher-order cognitive function and prepulse inhibition. Biol Psychol. 2013;93(1):17–23.

    Article  PubMed  Google Scholar 

  68. Gogos A, Wu YC, Williams AS, Byrne LK. The effects of ethinylestradiol and progestins (“the pill”) on cognitive function in pre-menopausal women. Neurochem Res. 2014;39(12):2288–300.

    Article  CAS  PubMed  Google Scholar 

  69. Cyr M, Calon F, Morissette M, Di Paolo T. Estrogenic modulation of brain activity: implications for schizophrenia and Parkinson’s disease. J Psychiatry Neurosci. 2002;27(1):12–27.

    PubMed  PubMed Central  Google Scholar 

  70. Nelson HD. Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review. JAMA. 2004;291(13):1610–20.

    Article  CAS  PubMed  Google Scholar 

  71. Resnick SM, Maki PM, Rapp SR, Espeland MA, Brunner R, Coker LH, et al. Effects of combination estrogen plus progestin hormone treatment on cognition and affect. J Clin Endocrinol Metab. 2006;91(5):1802–10.

    Article  CAS  PubMed  Google Scholar 

  72. Engler-Chiurazzi EB, Talboom JS, Braden BB, Tsang CWS, Mennenga S, Andrews M, et al. Continuous estrone treatment impairs spatial memory and does not impact number of basal forebrain cholinergic neurons in the surgically menopausal middle-aged rat. Horm Behav. 2012;62(1):1–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Luine VN, Richards ST, Wu VY, Beck KD. Estradiol enhances learning and memory in a spatial memory task and effects levels of monoaminergic neurotransmitters. Horm Behav. 1998;34(2):149–62.

    Article  CAS  PubMed  Google Scholar 

  74. Akhondzadeh S, Nejatisafa AA, Amini H, Mohammadi MR, Larijani B, Kashani L, et al. Adjunctive estrogen treatment in women with chronic schizophrenia: a double-blind, randomized, and placebo-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27(6):1007–12.

    Article  CAS  PubMed  Google Scholar 

  75. Kulkarni J, Riedel A, de Castella AR, Fitzgerald PB, Rolfe TJ, Taffe J, et al. Estrogen — a potential treatment for schizophrenia. Schizophr Res. 2001;48(1):137–44.

    Article  CAS  PubMed  Google Scholar 

  76. Kulkarni J, de Castella A, Smith D, Taffe J, Keks N, Copolov D. A clinical trial of the effects of estrogen in acutely psychotic women. Schizophr Res. 1996;20(3):247–52.

    Article  CAS  PubMed  Google Scholar 

  77. Ko Y-H, Joe S-H, Cho W, Park J-H, Lee J-J, Jung I-K, et al. Estrogen, cognitive function and negative symptoms in female schizophrenia. Neuropsychobiology. 2006;53(4):169–75.

    Article  CAS  PubMed  Google Scholar 

  78. Kulkarni J, Riedel A, de Castella AR, Fitzgerald PB, Rolfe TJ, Taffe J, et al. A clinical trial of adjunctive oestrogen treatment in women with schizophrenia. Arch Womens Ment Health. 2002;5(3):99–104.

    Article  CAS  PubMed  Google Scholar 

  79. Kulkarni J, de Castella A, Fitzgerald PB, Gurvich CT, Bailey M, Bartholomeusz C, et al. Estrogen in severe mental illness: a potential new treatment approach. Arch Gen Psychiatry. 2008;65(8):955–60.

    Article  PubMed  Google Scholar 

  80. Bergemann N, Mundt C, Parzer P, Pakrasi M, Eckstein-Mannsperger U, Haisch S, et al. Estrogen as an adjuvant therapy to antipsychotics does not prevent relapse in women suffering from schizophrenia: results of a placebo-controlled double-blind study. Schizophr Res. 2005;74(2–3):125–34.

    Article  PubMed  Google Scholar 

  81. Lindamer LA, Buse DC, Lohr JB, Jeste DV. Hormone replacement therapy in postmenopausal women with schizophrenia: positive effect on negative symptoms? Biol Psychiatry. 2001;49(1):47–51.

    Article  CAS  PubMed  Google Scholar 

  82. Hoff AL, Kremen WS, Wieneke MH, Lauriello J, et al. Association of estrogen levels with neuropsychological performance in women with schizophrenia. Am J Psychiatry. 2001;158(7):1134–9.

    Article  CAS  PubMed  Google Scholar 

  83. Bergemann N, Parzer P, Jaggy S, Auler B, Mundt C, Maier-Braunleder S. Estrogen and comprehension of metaphoric speech in women suffering from schizophrenia: results of a double-blind, placebo-controlled trial. Schizophr Bull. 2008;34(6):1172–81.

    Article  PubMed  Google Scholar 

  84. Gibbs RB. Estrogen therapy and cognition: a review of the cholinergic hypothesis. Endocr Rev. 2010;31(2):224–53.

    Article  CAS  PubMed  Google Scholar 

  85. Arad M, Weiner I. Contrasting effects of increased and decreased dopamine transmission on latent inhibition in ovariectomized rats and their modulation by 17β-estradiol: an animal model of menopausal psychosis? Neuropsychopharmacology. 2010;35(7):1570–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Arad M, Weiner I. Sex-dependent antipsychotic capacity of 17β-estradiol in the latent inhibition model: a typical antipsychotic drug in both sexes, atypical antipsychotic drug in males. Neuropsychopharmacology. 2010;35(11):2179–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Barha CK, Dalton GL, Galea LAM. Low doses of 17α-estradiol and 17β-estradiol facilitate, whereas higher doses of estrone and 17α- and 17β-estradiol impair, contextual fear conditioning in adult female rats. Neuropsychopharmacology. 2009;35(2):547–59.

    Article  PubMed Central  CAS  Google Scholar 

  88. Bimonte HA, Denenberg VH. Estradiol facilitates performance as working memory load increases. Psychoneuroendocrinology. 1999;24(2):161–73.

    Article  CAS  PubMed  Google Scholar 

  89. Bimonte-Nelson HA, Francis KR, Umphlet CD, Granholm A-C. Progesterone reverses the spatial memory enhancements initiated by tonic and cyclic oestrogen therapy in middle-aged ovariectomized female rats. Eur J Neurosci. 2006;24(1):229–42.

    Article  PubMed  Google Scholar 

  90. Bohacek J, Daniel JM. The beneficial effects of estradiol on attentional processes are dependent on timing of treatment initiation following ovariectomy in middle-aged rats. Psychoneuroendocrinology. 2010;35(5):694–705.

    Article  CAS  PubMed  Google Scholar 

  91. Chesler EJ, Juraska JM. Acute administration of estrogen and progesterone impairs the acquisition of the spatial Morris water maze in ovariectomized rats. Horm Behav. 2000;38(4):234–42.

    Article  CAS  PubMed  Google Scholar 

  92. Daniel JM, Fader AJ, Spencer AL, Dohanich GP. Estrogen enhances performance of female rats during acquisition of a radial arm maze. Horm Behav. 1997;32(3):217–25.

    Article  CAS  PubMed  Google Scholar 

  93. Daniel JM, Lee CD. Estrogen replacement in ovariectomized rats affects strategy selection in the Morris water maze. Neurobiol Learn Mem. 2004;82(2):142–9.

    Article  CAS  PubMed  Google Scholar 

  94. Daniel JM, Hulst JL, Berbling JL. Estradiol replacement enhances working memory in middle-aged rats when initiated immediately after ovariectomy but not after a long-term period of ovarian hormone deprivation. Endocrinology. 2006;147(1):607–14.

    Article  CAS  PubMed  Google Scholar 

  95. Davis DM, Jacobson TK, Aliakbari S, Mizumori SJY. Differential effects of estrogen on hippocampal- and striatal-dependent learning. Neurobiol Learn Mem. 2005;84(2):132–7.

    Article  CAS  PubMed  Google Scholar 

  96. Diaz-Veliz G, Urresta F, Dussaubat N, Mora S. Effects of estradiol replacement in ovariectomized rats on conditioned avoidance responses and other behaviors. Physiol Behav. 1991;50(1):61–5.

    Article  CAS  PubMed  Google Scholar 

  97. El-Bakri NK, Islam A, Zhu S, Elhassan A, Mohammed A, Winblad B, et al. Effects of estrogen and progesterone treatment on rat hippocampal NMDA receptors: relationship to Morris water maze performance. J Cell Mol Med. 2004;8(4):537–44.

    Article  CAS  PubMed  Google Scholar 

  98. Fader AJ, Hendricson AW, Dohanich GP. Estrogen improves performance of reinforced T-maze alternation and prevents the amnestic effects of scopolamine administered systemically or intrahippocampally. Neurobiol Learn Mem. 1998;69(3):225–40.

    Article  CAS  PubMed  Google Scholar 

  99. Fader AJ, Johnson PEM, Dohanich GP. Estrogen improves working but not reference memory and prevents amnestic effects of scopolamine on a radial-arm maze. Pharmacol Biochem Behav. 1999;62(4):711–7.

    Article  CAS  PubMed  Google Scholar 

  100. Feng Z, Cheng Y, Zhang J. Long-term effects of melatonin or 17β-estradiol on improving spatial memory performance in cognitively impaired, ovariectomized adult rats. J Pineal Res. 2004;37(3):198–206.

    Article  CAS  PubMed  Google Scholar 

  101. Frick KM, Fernandez SM, Bennett JC, Prange-Kiel J, MacLusky NJ, Leranth C. Behavioral training interferes with the ability of gonadal hormones to increase CA1 spine synapse density in ovariectomized female rats. Eur J Neurosci. 2004;19(11):3026–32.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Frye CA, Rhodes ME. Enhancing effects of estrogen on inhibitory avoidance performance may be in part independent of intracellular estrogen receptors in the hippocampus. Brain Res. 2002;956(2):285–93.

    Article  CAS  PubMed  Google Scholar 

  103. Frye CA, Duffy CK, Walf AA. Estrogens and progestins enhance spatial learning of intact and ovariectomized rats in the object placement task. Neurobiol Learn Mem. 2007;88(2):208–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Galea LAM, Wide JK, Paine TA, Holmes MM, Ormerod BK, Floresco SB. High levels of estradiol disrupt conditioned place preference learning, stimulus response learning and reference memory but have limited effects on working memory. Behav Brain Res. 2001;126(1–2):115–26.

    Google Scholar 

  105. Gibbs RB. Estrogen replacement enhances acquisition of a spatial memory task and reduces deficits associated with hippocampal muscarinic receptor inhibition. Horm Behav. 1999;36(3):222–33.

    Article  CAS  PubMed  Google Scholar 

  106. Gibbs RB. Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats. Neurobiol Aging. 2000;21(1):107–16.

    Article  CAS  PubMed  Google Scholar 

  107. Gibbs RB. Estradiol enhances DMP acquisition via a mechanism not mediated by turning strategy but which requires intact basal forebrain cholinergic projections. Horm Behav. 2007;52(3):352–9.

    Article  CAS  PubMed  Google Scholar 

  108. Gibbs RB, Johnson DA. Sex-specific effects of gonadectomy and hormone treatment on acquisition of a 12-arm radial maze task by Sprague Dawley rats. Endocrinology. 2008;149(6):3176–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Gogos A, van den Buuse M. Estrogen and progesterone prevent disruption of prepulse inhibition by the serotonin-1a receptor agonist 8-hydroxy-2-dipropylaminotetralin. J Pharmacol Exp Ther. 2004;309(1):267–74.

    Article  CAS  PubMed  Google Scholar 

  110. Gogos A, Kwek P, Chavez C, van den Buuse M. Estrogen treatment blocks 8-Hydroxy-2-Dipropylaminotetralin- and apomorphine-induced disruptions of prepulse inhibition: involvement of dopamine D1 or D2 or serotonin 5-HT1A, 5-HT2A, or 5-HT7 receptors. J Pharmacol Exp Ther. 2010;333(1):218–27.

    Article  CAS  PubMed  Google Scholar 

  111. Gogos A, Kwek P, van den Buuse M. The role of estrogen and testosterone in female rats in behavioral models of relevance to schizophrenia. Psychopharmacology (Berl). 2012;219(1):213–24.

    Article  CAS  Google Scholar 

  112. Hammond R, Mauk R, Ninaci D, Nelson D, Gibbs R. Chronic treatment with estrogen receptor agonists restores acquisition of a spatial learning task in young ovariectomized rats. Horm Behav. 2009;56(3):309–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Hawley WR, Grissom EM, Moody NM, Dohanich GP, Vasudevan N. Activation of G-protein-coupled receptor 30 is sufficient to enhance spatial recognition memory in ovariectomized rats. Behav Brain Res. 2014;262:68–73.

    Article  CAS  PubMed  Google Scholar 

  114. Hoffman AN, Armstrong CE, Hanna JJ, Conrad CD. Chronic stress, cyclic 17β-estradiol, and daily handling influences on fear conditioning in the female rat. Neurobiol Learn Mem. 2010;94(3):422–33.

    Article  CAS  PubMed  Google Scholar 

  115. Holmes MM, Wide JK, Galea LAM. Low levels of estradiol facilitate, whereas high levels of estradiol impair, working memory performance on the radial arm maze. Behav Neurosci. 2002;116(5):928–34.

    Article  CAS  PubMed  Google Scholar 

  116. Horvath KM, Hårtig W, Van der Veen R, Keijser JN, Mulder J, Ziegert M, et al. 17β-Estradiol enhances cortical cholinergic innervation and preserves synaptic density following excitotoxic lesions to the rat nucleus basalis magnocellularis. Neuroscience. 2002;110(3):489–504.

    Article  CAS  PubMed  Google Scholar 

  117. Jacome LF, Gautreaux C, Inagaki T, Mohan G, Alves S, Lubbers LS, et al. Estradiol and ERβ agonists enhance recognition memory, and DPN, an ERβ agonist, alters brain monoamines. Neurobiol Learn Mem. 2010;94(4):488–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Kiss A, Delattre AM, Pereira SIR, Carolino RG, Szawka RE, Anselmo-Franci JA, et al. 17β-Estradiol replacement in young, adult and middle-aged female ovariectomized rats promotes improvement of spatial reference memory and an antidepressant effect and alters monoamines and BDNF levels in memory- and depression-related brain areas. Behav Brain Res. 2012;227(1):100–8.

    Article  CAS  PubMed  Google Scholar 

  119. Korol DL, Kolo LL. Estrogen-induced changes in place and response learning in young adult female rats. Behav Neurosci. 2002;116(3):411–20.

    Article  CAS  PubMed  Google Scholar 

  120. Lipatova O, Toufexis DJ. Estrogen enhances the retention of spatial reference memory in the open field tower task, but disrupts the expression of spatial memory following a novel start position. Neurobiol Learn Mem. 2013;99:50–8.

    Article  CAS  PubMed  Google Scholar 

  121. Lipatova O, Byrd D, Green JT, Toufexis DJ. Effects of continuous vs. cycling estrogen replacement on the acquisition, retention and expression of place- and response-learning in the open-field tower maze. Neurobiol Learn Mem. 2014;114:81–9.

    Article  CAS  PubMed  Google Scholar 

  122. Liu J, Lin H, Huang Y, Liu Y, Wang B, Su F. Cognitive effects of long-term dydrogesterone treatment used alone or with estrogen on rat menopausal models of different ages. Neuroscience. 2015;290:103–14.

    Article  CAS  PubMed  Google Scholar 

  123. Lowry NC, Pardon LP, Yates MA, Juraska JM. Effects of long-term treatment with 17 β-estradiol and medroxyprogesterone acetate on water maze performance in middle aged female rats. Horm Behav. 2010;58(2):200–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Luine VN, Rodriguez M. Effects of estradiol on radial arm maze performance of young and aged rats. Behav Neural Biol. 1994;62(3):230–6.

    Article  CAS  PubMed  Google Scholar 

  125. Markham JA, Pych JC, Juraska JM. Ovarian hormone replacement to aged ovariectomized female rats benefits acquisition of the morris water maze. Horm Behav. 2002;42(3):284–93.

    Article  CAS  PubMed  Google Scholar 

  126. Markowska AL, Savonenko AV. Effectiveness of estrogen replacement in restoration of cognitive function after long-term estrogen withdrawal in aging rats. J Neurosci Off J Soc Neurosci. 2002;22(24):10985–95.

    CAS  Google Scholar 

  127. McLaughlin KJ, Bimonte-Nelson H, Neisewander JL, Conrad CD. Assessment of estradiol influence on spatial tasks and hippocampal CA1 spines: Evidence that the duration of hormone deprivation after ovariectomy compromises 17β-estradiol effectiveness in altering CA1 spines. Horm Behav. 2008;54(3):386–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Nofrey BS, Ben-Shahar OM, Brake WG. Estrogen abolishes latent inhibition in ovariectomized female rats. Brain Cogn. 2008;66(2):156–60.

    Article  PubMed  Google Scholar 

  129. Packard MG, Teather LA. Posttraining estradiol injections enhance memory in ovariectomized rats: cholinergic blockade and synergism. Neurobiol Learn Mem. 1997;68(2):172–88.

    Article  CAS  PubMed  Google Scholar 

  130. Ping SE, Trieu J, Wlodek ME, Barrett GL. Effects of estrogen on basal forebrain cholinergic neurons and spatial learning. J Neurosci Res. 2008;86(7):1588–98.

    Article  CAS  PubMed  Google Scholar 

  131. Rhodes ME, Frye CA. Estrogen has mnemonic-enhancing effects in the inhibitory avoidance task. Pharmacol Biochem Behav. 2004;78(3):551–8.

    Article  CAS  PubMed  Google Scholar 

  132. Rhodes ME, Frye CA. ERβ-selective SERMs produce mnemonic-enhancing effects in the inhibitory avoidance and water maze tasks. Neurobiol Learn Mem. 2006;85(2):183–91.

    Article  CAS  PubMed  Google Scholar 

  133. Rodgers SP, Bohacek J, Daniel JM. Transient estradiol exposure during middle age in ovariectomized rats exerts lasting effects on cognitive function and the hippocampus. Endocrinology. 2010;151(3):1194–203.

    Article  CAS  PubMed  Google Scholar 

  134. Roseman AS, McGregor C, Thornton JE. Estradiol attenuates the cognitive deficits in the novel object recognition task induced by sub-chronic phencyclidine in ovariectomized rats. Behav Brain Res. 2012;233(1):105–12.

    Article  CAS  PubMed  Google Scholar 

  135. Sandstrom NJ, Williams CL. Memory retention is modulated by acute estradiol and progesterone replacement. Behav Neurosci. 2001;115(2):384–93.

    Article  CAS  PubMed  Google Scholar 

  136. Savonenko AV, Markowska AL. The cognitive effects of ovariectomy and estrogen replacement are modulated by aging. Neuroscience. 2003;119(3):821–30.

    Article  CAS  PubMed  Google Scholar 

  137. Singh M, Meyer EM, Millard WJ, Simpkins JW. Ovarian steroid deprivation results in a reversible learning impairment and compromised cholinergic function in female Sprague–Dawley rats. Brain Res. 1994;644(2):305–12.

    Article  CAS  PubMed  Google Scholar 

  138. Sinopoli KJ, Floresco SB, Galea LAM. Systemic and local administration of estradiol into the prefrontal cortex or hippocampus differentially alters working memory. Neurobiol Learn Mem. 2006;86(3):293–304.

    Article  CAS  PubMed  Google Scholar 

  139. Talboom JS, Williams BJ, Baxley ER, West SG, Bimonte-Nelson HA. Higher levels of estradiol replacement correlate with better spatial memory in surgically menopausal young and middle-aged rats. Neurobiol Learn Mem. 2008;90(1):155–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Tanabe F, Miyasaka N, Kubota T, Aso T. Estrogen and progesterone improve scopolamine-induced impairment of spatial memory. J Med Dent Sci. 2004;51(1):89–98.

    PubMed  Google Scholar 

  141. Thwaites SJ, van den Buuse M, Gogos A. Differential effects of estrogen and testosterone on auditory sensory gating in rats. Psychopharmacology (Berl). 2014;231(1):243–56.

    Article  CAS  Google Scholar 

  142. Vaillancourt C, Cyr M, Rochford J, Boksa P, Di Paolo T. Effects of ovariectomy and estradiol on acoustic startle responses in rats. Pharmacol Biochem Behav. 2002;74(1):103–9.

    Article  CAS  PubMed  Google Scholar 

  143. van den Buuse M, Eikelis N. Estrogen increases prepulse inhibition of acoustic startle in rats. Eur J Pharmacol. 2001;425(1):33–41.

    Article  PubMed  Google Scholar 

  144. van den Buuse M, Mingon RL, Gogos A. Chronic estrogen and progesterone treatment inhibits ketamine-induced disruption of prepulse inhibition in rats. Neurosci Lett. 2015;607:72–6.

    Article  PubMed  CAS  Google Scholar 

  145. Velázquez-Zamora DA, Garcia-Segura LM, González-Burgos I. Effects of selective estrogen receptor modulators on allocentric working memory performance and on dendritic spines in medial prefrontal cortex pyramidal neurons of ovariectomized rats. Horm Behav. 2012;61(4):512–7.

    Article  PubMed  CAS  Google Scholar 

  146. Walf AA, Rhodes ME, Frye CA. Ovarian steroids enhance object recognition in naturally cycling and ovariectomized, hormone-primed rats. Neurobiol Learn Mem. 2006;86(1):35–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Walf AA, Paris JJ, Frye CA. Chronic estradiol replacement to aged female rats reduces anxiety-like and depression-like behavior and enhances cognitive performance. Psychoneuroendocrinology. 2009;34(6):909–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Wang VC, Sable HJK, Ju YH, Allred CD, Helferich WG, Korol DL, et al. Effects of chronic estradiol treatment on delayed spatial alternation and differential reinforcement of low rates of responding. Behav Neurosci. 2008;122(4):794–804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Wang VC, Neese SL, Korol DL, Schantz SL. Chronic estradiol replacement impairs performance on an operant delayed spatial alternation task in young, middle-aged, and old rats. Horm Behav. 2009;56(4):382–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Wide JK, Hanratty K, Ting J, Galea LAM. High level estradiol impairs and low level estradiol facilitates non-spatial working memory. Behav Brain Res. 2004;155(1):45–53.

    Article  CAS  PubMed  Google Scholar 

  151. Witty CF, Gardella LP, Perez MC, Daniel JM. Short-term estradiol administration in aging ovariectomized rats provides lasting benefits for memory and the hippocampus: a role for insulin-like growth factor-I. Endocrinology. 2012;154(2):842–52.

    Article  PubMed  CAS  Google Scholar 

  152. Wu J, Zhu Y, Wu J. Effects of estrogen and estrogenic compounds on cognition in ovariectomized rats. Climacteric. 2008;11(3):212–20.

    Article  CAS  PubMed  Google Scholar 

  153. Zurkovsky L, Brown SL, Korol DL. Estrogen modulates place learning through estrogen receptors in the hippocampus. Neurobiol Learn Mem. 2006;86(3):336–43.

    Article  CAS  PubMed  Google Scholar 

  154. Zurkovsky L, Brown SL, Boyd SE, Fell JA, Korol DL. Estrogen modulates learning in female rats by acting directly at distinct memory systems. Neuroscience. 2007;144(1):26–37.

    Article  CAS  PubMed  Google Scholar 

  155. Ziegler DR, Gallagher M. Spatial memory in middle-aged female rats: assessment of estrogen replacement after ovariectomy. Brain Res. 2005;1052(2):163–73.

    Article  CAS  PubMed  Google Scholar 

  156. Desbonnet L, Waddington JL, O’Tuathaigh CMP. Mutant models for genes associated with schizophrenia. Biochem Soc Trans. 2009;37(1):308.

    Article  CAS  PubMed  Google Scholar 

  157. van den Buuse M. Modeling the positive symptoms of schizophrenia in genetically modified mice: pharmacology and methodology aspects. Schizophr Bull. 2010;36(2):246–70.

    Article  PubMed  Google Scholar 

  158. Braff DL, Light GA. The use of neurophysiological endophenotypes to understand the genetic basis of schizophrenia. Dialogues Clin Neurosci. 2005;7(2):125–35.

    PubMed  PubMed Central  Google Scholar 

  159. Gogos A, van den Buuse M. Castration reduces the effect of Serotonin-1A receptor stimulation on prepulse inhibition in rats. Behav Neurosci. 2003;117(6):1407–15.

    Article  CAS  PubMed  Google Scholar 

  160. Sutcliffe JS, Rhaman F, Marshall KM, Neill JC. Oestradiol attenuates the cognitive deficit induced by acute phencyclidine treatment in mature female hooded-Lister rats. J Psychopharmacol (Oxf). 2008;22(8):918–22.

    Article  CAS  Google Scholar 

  161. Sánchez MG, Bourque M, Morissette M, Di Paolo T. Steroids–dopamine interactions in the pathophysiology and treatment of CNS disorders. CNS Neurosci Ther. 2010;16(3):e43–71.

    Article  PubMed  CAS  Google Scholar 

  162. Dhingra K. Antiestrogens — tamoxifen, SERMs and beyond. Invest New Drugs. 1999;17(3):285–311.

    Article  CAS  PubMed  Google Scholar 

  163. Maximov PY, Lee TM, Jordan VC. The discovery and development of selective estrogen receptor modulators (SERMs) for clinical practice. Curr Clin Pharmacol. 2013;8(2):135–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Janicki SC, Schupf N. Hormonal influences on cognition and risk for alzheimer disease. Curr Neurol Neurosci Rep. 2010;10(5):359–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Calmarza-Font I, Lagunas N, Garcia-Segura LM. Antidepressive and anxiolytic activity of selective estrogen receptor modulators in ovariectomized mice submitted to chronic unpredictable stress. Behav Brain Res. 2012;227(1):287–90.

    Article  CAS  PubMed  Google Scholar 

  166. Legault C, Maki PM, Resnick SM, Coker L, Hogan P, Bevers TB, et al. Effects of tamoxifen and raloxifene on memory and other cognitive abilities: cognition in the study of tamoxifen and raloxifene. J Clin Oncol. 2009;27(31):5144–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Fisher B, Costantino JP, Redmond CK, Fisher ER, Wickerham DL, Cronin WM, et al. Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst. 1994;86(7):527–37.

    Article  CAS  PubMed  Google Scholar 

  168. Kulkarni J, Gurvich C, Lee SJ, Gilbert H, Gavrilidis E, de Castella A, et al. Piloting the effective therapeutic dose of adjunctive selective estrogen receptor modulator treatment in postmenopausal women with schizophrenia. Psychoneuroendocrinology. 2010;35(8):1142–7.

    Article  CAS  PubMed  Google Scholar 

  169. Kianimehr G, Fatehi F, Hashempoor S, Khodaei-Ardakani M-R, Rezaei F, Nazari A, et al. Raloxifene adjunctive therapy for postmenopausal women suffering from chronic schizophrenia: a randomized double-blind and placebo controlled trial. DARU J Pharm Sci. 2014;22(1):55.

    Article  CAS  Google Scholar 

  170. Usall J, Huerta-Ramos E, Iniesta R, Cobo J, Araya S, Roca M, et al. Raloxifene as an adjunctive treatment for postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry. 2011;72(11):1552.

    Article  CAS  PubMed  Google Scholar 

  171. Usall J, Huerta-Ramos E, Labad J, Cobo J, Núñez C, Creus M, et al. Raloxifene as an adjunctive treatment for postmenopausal women with schizophrenia: a 24-week double-blind, randomized, parallel, placebo-controlled trial. Schizophr Bull. 2016;46:309–17.

    Article  Google Scholar 

  172. Weickert TW, Weinberg D, Lenroot R, Catts SV, Wells R, Vercammen A, et al. Adjunctive raloxifene treatment improves attention and memory in men and women with schizophrenia. Mol Psychiatry. 2015;20(6):685–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Buwalda B, Schagen SB. Is basic research providing answers if adjuvant anti-estrogen treatment of breast cancer can induce cognitive impairment? Life Sci. 2013;93(17):581–8.

    Article  CAS  PubMed  Google Scholar 

  174. O’Neill K, Chen S, Brinton RD. Impact of the selective estrogen receptor modulator, raloxifene, on neuronal survival and outgrowth following toxic insults associated with aging and Alzheimer’s disease. Exp Neurol. 2004;185(1):63–80.

    Article  PubMed  CAS  Google Scholar 

  175. Khodaie-Ardakani M-R, Khosravi M, Zarinfard R, Nejati S, Mohsenian A, Tabrizi M, et al. A placebo-controlled study of raloxifene added to risperidone in men with chronic schizophrenia. Acta Med Iran. 2015;53(6):337–45.

    PubMed  Google Scholar 

  176. Huerta-Ramos E, Iniesta R, Ochoa S, Cobo J, Miquel E, Roca M, et al. Effects of raloxifene on cognition in postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial. Eur Neuropsychopharmacol. 2014;24(2):223–31.

    Article  CAS  PubMed  Google Scholar 

  177. Kulkarni J, Gurvich C, Gilbert H, Mehmedbegovic F, Mu L, Marston N, et al. Hormone modulation: a novel therapeutic approach for women with severe mental illness. Aust N Z J Psychiatry. 2008;42(1):83–8.

    Article  PubMed  Google Scholar 

  178. Sharma E, Raveendranathan D, Shivakumar V, Jayaram N, Rao NP, Venkatasubramanian G. Beneficial effects of add-on raloxifene in schizophrenia. Arch Womens Ment Health. 2012;15(2):147–8.

    Article  Google Scholar 

  179. Wong J, Seeman M, Shapiro H. Case report — raloxifene in postmenopausal women with psychosis: preliminary findings. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry. 2003;11(6):697–8.

    Google Scholar 

  180. Espeland MA, Shumaker SA, Limacher M, Rapp SR, Bevers TB, Barad DH, et al. Relative effects of tamoxifen, raloxifene, and conjugated equine estrogens on cognition. J Womens Health. 2010;19(3):371–9.

    Article  Google Scholar 

  181. Jacobsen DE, Samson MM, Emmelot-Vonk MH, Verhaar HJJ. Raloxifene improves verbal memory in late postmenopausal women: a randomized, double-blind, placebo-controlled trial. Menopause. 2010;17(2):309–14.

    Article  PubMed  Google Scholar 

  182. Yaffe K, Krueger K, Cummings SR, Blackwell T, Henderson VW, Sarkar S, et al. Effect of raloxifene on prevention of dementia and cognitive impairment in older women: the multiple outcomes of raloxifene evaluation (MORE) randomized trial. Am J Psychiatry. 2005;162(4):683–90.

    Article  PubMed  Google Scholar 

  183. Cabeza R, Nyberg L. Imaging Cognition II: an empirical review of 275 PET and fMRI studies. J Cogn Neurosci. 2000;12(1):1–47.

    Article  CAS  PubMed  Google Scholar 

  184. Kulkarni J, de Castella A, Headey B, Marston N, Sinclair K, Lee S, et al. Estrogens and men with schizophrenia: is there a case for adjunctive therapy? Schizophr Res. 2011;125(2–3):278–83.

    Article  PubMed  Google Scholar 

  185. Lagunas N, Calmarza-Font I, Grassi D, Garcia-Segura LM. Estrogen receptor ligands counteract cognitive deficits caused by androgen deprivation in male rats. Horm Behav. 2011;59(4):581–4.

    Article  CAS  PubMed  Google Scholar 

  186. Hao J, Rapp PR, Leffler AE, Leffler SR, Janssen WGM, Lou W, et al. Estrogen alters spine number and morphology in prefrontal cortex of aged female rhesus monkeys. J Neurosci. 2006;26(9):2571–8.

    Article  CAS  PubMed  Google Scholar 

  187. Rapp PR, Morrison JH, Roberts JA. Cyclic estrogen replacement improves cognitive function in aged ovariectomized Rhesus monkeys. J Neurosci. 2003;23(13):5708–14.

    CAS  PubMed  Google Scholar 

  188. Gibbs RB, Gabor R, Cox T, Johnson DA. Effects of raloxifene and estradiol on hippocampal acetylcholine release and spatial learning in the rat. Psychoneuroendocrinology. 2004;29(6):741–8.

    Article  CAS  PubMed  Google Scholar 

  189. Lacreuse A, Wilson ME, Herndon JG. Estradiol, but not raloxifene, improves aspects of spatial working memory in aged ovariectomized rhesus monkeys. Neurobiol Aging. 2002;23(4):589–600.

    Article  CAS  PubMed  Google Scholar 

  190. Vasudevan N, Pfaff DW. Non-genomic actions of estrogens and their interaction with genomic actions in the brain. Front Neuroendocrinol. 2008;29(2):238–57.

    Article  CAS  PubMed  Google Scholar 

  191. Morrison JH, Brinton RD, Schmidt PJ, Gore AC. Estrogen, menopause, and the aging brain: how basic neuroscience can inform hormone therapy in women. J Neurosci. 2006;26(41):10332–48.

    Article  CAS  PubMed  Google Scholar 

  192. Seeman P. Atypical antipsychotics: mechanism of action. FOCUS J Lifelong Learn Psychiatry. 2004;2(1):48–58.

    Google Scholar 

  193. Barnes P, Staal V, Muir J, Good MA. 17-β estradiol administration attenuates deficits in sustained and divided attention in young ovariectomized rats and aged acyclic female rats. Behavioral Neuroscience. 2006;120(6):1225–34. https://doi.org/10.1037/0735-7044.120.6.1225

Download references

Author information

Authors and Affiliations

  1. Florey Institute of Neuroscience and Mental Health, University of Melbourne, 30 Royal Parade, Parkville, Melbourne, VIC, 3052, Australia

    Alyssa M. Sbisa BAppSc (Hons) & Andrea Gogos

  2. School of Psychology and Public Health, La Trobe University, Bundoora, VIC, 3086, Australia

    Alyssa M. Sbisa BAppSc (Hons) & Maarten van den Buuse

Authors
  1. Alyssa M. Sbisa BAppSc (Hons)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maarten van den Buuse
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrea Gogos
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. National University of Cuyo, Catholic University of Argentina, Guaymallen Mendoza, Argentina

    Pascual Ángel Gargiulo

  2. Institute of Neurobiology Foundation, National Academy of Medicine, Buenos Aires, Argentina

    Humberto Luis Mesones-Arroyo

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Sbisa, A.M., van den Buuse, M., Gogos, A. (2017). The Effect of 17β-Estradiol and Its Analogues on Cognition in Preclinical and Clinical Research: Relevance to Schizophrenia. In: Gargiulo, P., Mesones-Arroyo, H. (eds) Psychiatry and Neuroscience Update - Vol. II. Springer, Cham. https://doi.org/10.1007/978-3-319-53126-7_26

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-53126-7_26

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-53125-0

  • Online ISBN: 978-3-319-53126-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation