Conjugated equine estrogen, with medroxyprogesterone acetate, enhances formation of 5α-reduced progestogens and reduces anxiety-like behavior of middle-aged rats

Behavioural Pharmacology

Volumn 21, Issue 5-6, 2010, Pages 530-539

  Frye, Cheryl A ^a   Walf, Alicia A ^a   Paris, Jason J ^a  

^a STATE UNIVERSITY OF NEW YORK   (United States)

Author keywords

Anxiety; conjugated equine estrogen; estradiol; medroxyprogesterone acetate; menopause; premarin; prempro; progesterone; rat

Indexed keywords

CONJUGATED ESTROGEN; ESTRADIOL; GESTAGEN; MEDROXYPROGESTERONE ACETATE; PROGESTERONE;

AGED; ANIMAL EXPERIMENT; ANIMAL MODEL; ANXIETY; ARTICLE; CONTROLLED STUDY; FEMALE; HIPPOCAMPUS; HORMONE METABOLISM; MAZE TEST; NONHUMAN; OPEN FIELD BEHAVIOR; RAT; SOCIAL INTERACTION;

20-ALPHA-DIHYDROPROGESTERONE; ANIMALS; ANXIETY; BEHAVIOR, ANIMAL; DESOXYCORTICOSTERONE; DISEASE MODELS, ANIMAL; DRUG THERAPY, COMBINATION; ESTROGENS, CONJUGATED (USP); FEMALE; HIPPOCAMPUS; MAZE LEARNING; MEDROXYPROGESTERONE ACETATE; PROGESTERONE; RATS; RATS, LONG-EVANS;

EID: 77955981868     PISSN: 09558810     EISSN: None     Source Type: Journal    
DOI: 10.1097/FBP.0b013e32833e0a23     Document Type: Article

References (75)

1. Acosta JI, Mayer L, Talboom JS, Zay C, Scheldrup M, Castillo J, et al. (2009). Premarin improves memory, prevents scopolamine-induced amnesia and increases number of basal forebrain choline acetyltransferase positive cells in middle-aged surgically menopausal rats. Horm Behav 55:454-464.
2. Barha CK, Galea LA (2010a). Influence of different estrogens on neuroplasticity and cognition in the hippocampus. Biochim Biophys Acta (in press).
3. Barha CK, Galea LA (2010b). Motherhood alters the cellular response to estrogens in the hippocampus later in life. Neurobiol Aging (in press).
4. Bhavnani BR (1998). Pharmacokinetics and pharmacodynamics of conjugated equine estrogens: chemistry and metabolism. Proc Soc Exp Biol Med 217:6-16.
5. Bohacek J, Daniel JM (2010). The beneficial effects of estradiol on attentional processes are dependent on timing of treatment initiation following ovariectomy in middle-aged rats. Psychoneuroendocrinology 35:694-705.
6. Bohacek J, Bearl AM, Daniel JM (2008). Long-term ovarian hormone deprivation alters the ability of subsequent oestradiol replacement to regulate choline acetyltransferase protein levels in hippocampus and prefrontal cortex of middle-aged rats. J Neuroendocrinol 20:1023-1027.
7. Braden BB, Talboom JS, Crain ID, Simard AR, Lukas RJ, Prokai L, et al. (2010). Medroxyprogesterone acetate impairs memory and alters the GABAergic system in aged surgically menopausal rats. Neurobiol Learn Mem 93:444-453.
8. Byrnes EM, Bridges RS (2006). Reproductive experience alters anxiety-like behavior in the female rat. Horm Behav 50:70-76.
9. Chakraborty TR, Gore AC (2004). Aging-related changes in ovarian hormones, their receptors, and neuroendocrine function. Exp Biol Med 229:977-987.
10. Cheng YJ, Karavolas HJ (1973). Conversion of progesterone to 5a-pregnane-3, 20-dione and 3a-hydroxy-5a-pregnan-20-one by rat medical basal hypotha-lami and the effects of estradiol and stage of estrous cycle on the conversion. Endocrinology 93:1157-1162.
11. Ciriza I, Carrero P, Frye CA, Garcia-Segura LM (2006). Reduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus. The synthetic progestin medroxyprogesterone acetate (Provera) is not neuroprotective. J Neurobiol 66:916-928.
12. Craig MC, Maki PM, Murphy DG (2005). The Women's Health Initiative Memory Study: findings and implications for treatment. Lancet Neurol 4:190-194.
13. Daniel JM, Bohacek J (2010). The critical period hypothesis of estrogen effects on cognition: insights from basic research. Biochim Biophys Acta (in press).
14. Daniel JM, Hulst JL, Berbling JL (2006). 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 147:607-614.
15. Diaz Brinton R, Chen S, Montoya M, Hsieh D, Minaya J, Kim J, et al. (2000). The women's health initiative estrogen replacement therapy is neurotrophic and neuroprotective. Neurobiol Aging 21:475-496.
16. Engler-Chiurazzi E, Tsang C, Nonnenmacher S, Liang WS, Corneveaux JJ, Prokai L, et al. (2010). Tonic Premarin dose-dependently enhances memory, affects neurotrophin protein levels and alters gene expression in middle-aged rats. Neurobiol Aging (in press).
17. Estrada-Camarena E, López-Rubalcava C, Vega-Rivera N, Récamier-Carballo S, Fernández-Guasti A (2010). Antidepressant effects of estrogens: a basic approximation. Behav Pharmacol (in press).
18. Freeman ME (1988). The ovarian cycle of the rat. In: Knobil E, Neil J, editors. Physiology of reproduction. New York, NY: Raven Press Ltd.; pp. 1893-1928.
19. Frye CA (2009). Neurosteroids-from basic research to clinical perspectives. In: Rubin RT, Pfaff DW, editors. Hormones, brain, and behaviour. San Diego: Academic Press; pp. 395-416.
20. Frye CA, Walf AA (2002). Changes in progesterone metabolites in the hippocampus can modulate open field and forced swim test behavior of proestrous rats. Horm Behav 41:306-315.
21. Frye CA, Rhodes ME (2005). Estrogen-priming can enhance progesterone's anti-seizure effects in part by increasing hippocampal levels of allopregnanolone. Pharmacol Biochem Behav 81:907-916.
22. Frye CA, Walf AA (2007). The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2:322-328.
23. Frye CA, Walf AA (2008). Progesterone enhances performance of aged mice in cortical or hippocampal tasks. Neurosci Lett 437:116-120.
24. Frye CA, Petralia SM, Rhodes ME (2000). Estrous cycle and sex differences in performance on anxiety tasks coincide with increases in hippocampal progesterone and 3a,5a-THP. Pharmacol Biochem Behav 67:587-596.
25. Frye CA, Walf AA, Rhodes ME, Harney JP (2004). Progesterone enhances motor, anxiolytic, analgesic, and antidepressive behavior of wild-type mice, but not those deficient in type 1 5a-reductase. Brain Res 1004:116-124.
26. Frye CA, Paris JJ, Rhodes ME (2007). Engaging in paced mating, but neither exploratory, anti-anxiety, nor social behavior, increases 5a-reduced progestin concentrations in midbrain, hippocampus, striatum, and cortex. Reproduction 133:663-674.
27. Frye CA, Koonce CJ, Walf AA (2010a). Mnemonic effects of progesterone to mice require formation of 3a,5a-THP. Neuroreport 21:590-595.
28. Frye CA, Paris JJ, Walf AA (2010b). Transition to reproductive senescence of middle-aged female rats is associated with decrements in courtship aspects of mating behavior. Brain Research (in preparation).
29. Galea LA (2008). Gonadal hormone modulation of neurogenesis in the dentate gyrus of adult male and female rodents. Brain Res Rev 57:332-341.
30. Gatewood JD, Morgan MD, Eaton M, McNamara IM, Stevens LF, Macbeth AH, et al. (2005). Motherhood mitigates aging-related decrements in learning and memory and positively affects brain aging in the rat. Brain Res Bull 66:91-98.
31. Genazzani AR, Stomati M, Bernardi F, Luisi S, Casarosa E, Puccetti S, et al. (2004). Conjugated equine estrogens reverse the effects of aging on central and peripheral allopregnanolone and b-endorphin levels in female rats. Fertil Steril 81:757-766.
32. Gibbs RB (2000). Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats. Neurobiol Aging 21:107-116.
33. Greenspan SL, Resnick NM, Parker RA (2005). The effect of hormone replacement on physical performance in community-dwelling elderly women. Am J Med 118:1232-1239.
34. Hodges DR, Karavolas HJ (1992). Pituitary progestin-metabolizing enzyme activities in the aged female rat. J Steroid Biochem Mol Biol 41:79-84.
35. Huang HH, Steger RW, Bruni JF, Meites J (1978). Patterns of sex steroid and gonadotropin secretion in aging female rats. Endocrinology 103:1855-1859.
36. Jensen EV, Jacobson HI, Walf AA, Frye CA (2010). Estrogen action: a historic perspective on the implications of considering alternative approaches. Physiol Behav 99:151-162.
37. Kinsley CH, Madonia L, Gifford GW, Tureski K, Griffin GR, Lowry C, et al. (1999). Motherhood improves learning and memory. Nature 402:137-138.
38. Littleton-Kearney MT, Klaus JA, Hurn PD (2005). Effects of combined oral conjugated estrogens and medroxyprogesterone acetate on brain infarction size after experimental stroke in rat. J Cereb Blood Flow Metab 25:421-426.
39. Lokuge S, Frey BN, Foster JA, Soares CN, Steiner M (2010). The rapid effects of estrogen: a mini-review. Behav Pharmacol (in press).
40. Long JA, Evans HM (1929). The estrous cycle in the rat and its associated phenomena. Memories Univ California 6:1-148.
41. Lowry NC, Pardon LP, Yates MA, Juraska JM (2010). Effects of long-term treatment with 17 beta-estradiol and medroxyprogesterone acetate on water maze performance in middle aged female rats. Horm Behav 58:200-207.
42. Lu KH, Hopper BR, Vargo TM, Yen SS (1979). Chronological changes in sex steroid, gonadotropin and prolactin secretions in aging female rats displaying different reproductive states. Biol Reprod 21:193-203.
43. Macbeth AH, Scharfman HE, Maclusky NJ, Gautreaux C, Luine VN (2008). Effects of multiparity on recognition memory, monoaminergic neurotransmit-ters, and brain-derived neurotrophic factor (BDNF). Horm Behav 54:7-17.
44. Marrone BL, Karavolas HJ (1982). Progesterone metabolism by the hypothala-mus, pituitary, and uterus of the aged rat. Endocrinology 111:162-167.
45. Nass TE, LaPolt PS, Judd HL, Lu JK (1984). Alterations in ovarian steroid and gonadotrophin secretion preceding the cessation of regular oestrous cycles in ageing female rats. J Endocrinol 100:43-50.
46. Nelson RJ (2005). An introduction to behavioral endocrinology. 3rd ed. Sunderland, MA: Sinauer Associates.
47. Nilsen J, Brinton RD (2002). Impact of progestins on estrogen-induced neuro-protection: synergy by progesterone and 19-norprogesterone and antagonism by medroxyprogesterone acetate. Endocrinol 143:205-212.
48. Paris JJ, Frye CA (2008). Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks. Reproduction 136:105-115.
49. Paris JJ, Walf AA, Frye CA (2010). Improved cognitive performance among middle-aged female rats is influenced by capacity to metabolize progesterone in the prefrontal cortex and hippocampus. Brain Res (submitted).
50. Pawluski JL, Walker SK, Galea LA (2006a). Reproductive experience differentially affects spatial reference and working memory performance in the mother. Horm Behav 49:143-149.
51. Pawluski JL, Vanderbyl BL, Ragan K, Galea LA (2006b). First reproductive experience persistently affects spatial reference and working memory in the mother and these effects are not due to pregnancy or mothering alone. Behav Brain Res 175:157-165.
52. Penning TM, Sharp RB, Krieger NR (1985). Purification and properties of 3 alpha-hydroxysteroid dehydrogenase from rat brain cytosol. Inhibition by nonsteroidal anti-inflammatory drugs and progestins. J Biol Chem 260:15266-15272.
53. Rhodes ME, Frye CA (2001). Inhibiting progesterone metabolism in the hippocampus of rats in behavioral estrus decreases anxiolytic behaviors and enhances exploratory and antinociceptive behaviors. Cogn Affect Behav Neurosci 1:287-296.
54. Sherwin BB (2007). The critical period hypothesis: can it explain discrepancies in the oestrogen-cognition literature? J Neuroendocrinol 19:77-81.
55. Sherwin BB (2009). Estrogen therapy: is time of initiation critical for neuroprotection? Nat Rev Endocrinol 5:620-627.
56. Sherwin BB, Henry JF (2008). Brain aging modulates the neuroprotective effects of estrogen on selective aspects of cognition in women: a critical review. Front Neuroendocrinol 29:88-113.
57. Soares CN, Prouty J, Born L, Steiner M (2005). Treatment of menopause-related mood disturbances. CNS Spectr 10:489-497.
58. Somers JM, Goldner EM, Waraich P, Hsu L (2006). Prevalence and incidence studies of anxiety disorders: a systematic review of the literature. Can J Psychiatry 51:100-103.
59. Steiner M, Dunn E, Born L (2003). Hormones and mood: from menarche to menopause and beyond. J Affect Disord 74:67-83.
60. Stern MD (1982). Pharmacology of conjugated oestrogens. Maturitas 4:333-339.
61. Taksande BG, Kotagale NR, Patel MR, Shelkar GP, Ugale RR, Chopde CT (2010). Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats. Eur J Pharmacol 637:89-101.
62. Toufexis DJ, Davis C, Hammond A, Davis M (2004). Progesterone attenuates corticotropin-releasing factor-enhanced but not fear-potentiated startle via the activity of its neuroactive metabolite, allopregnanolone. J Neurosci 24:10280-10287.
63. Vongher JM, Frye CA (1999). Progesterone in conjunction with estradiol has neuroprotective effects in an animal model of neurodegeneration. Pharmacol Biochem Behav 64:777-785.
64. Walf AA, Frye CA (2002). Changes in progesterone metabolites in the hippocampus can modulate open field and forced swim test behavior of proestrous rats. Horm Behav 41:306-315.
65. Walf AA, Frye CA (2008a). Conjugated equine estrogen enhances rats' cognitive, anxiety, & social behavior. Neuroreport 19:789-792.
66. Walf AA, Frye CA (2008b). Parity and estrogen-administration alter affective behavior of ovariectomized rats. Physiol Behav 93:351-356.
67. Walf AA, Frye CA (2009a). Estradiol enhances sociosexual behavior and can have proliferative effects in ovariectomized rats. Age 31:221-229.
68. Walf AA, Frye CA (2009b). Effects of two estradiol regimens on anxiety and depressive behaviors and trophic effects in peripheral tissues in a rodent model. Gend Med 6:300-311.
69. Walf AA, Frye CA (2010). Raloxifene and/or estradiol decrease anxiety-like and depressive-like behavior, whereas only estradiol increases carcinogen-induced tumorigenesis and uterine proliferation among ovariectomized rats. Behav Pharm 21:231-240.
70. Walf AA, Rhodes ME, Frye CA (2006). Ovarian steroids enhance object recognition in naturally cycling and ovariectomized, hormone-primed rats. Neurobiol Learn Mem 86:35-46.
71. Walf AA, Paris JJ, Frye CA (2009a). Middle-aged rats undergoing reproductive senescence demonstrate more anxiety-like, but not nociceptive, behavior than do reproductively competent rats of the same age. Gend Med 6:235-246.
72. Walf AA, Paris JJ, Frye CA (2009b). Chronic estradiol replacement to aged female rats reduces anxiety-like and depression-like behavior and enhances cognitive performance. Psychoneuroendocrinology 34:909-916.
73. Wise PM (1999). Neuroendocrine modulation of the menopause: insights into the aging brain. Am J Physiol 277:E965-E970.
74. Wright DW, Hoffman SW, Virmani S, Stein DG (2008). Effects of medroxypro-gesterone acetate on cerebral oedema and spatial learning performance after traumatic brain injury in rats. Brain Inj 22:107-113.
75. Zhao L, Brinton RD (2006). Select estrogens within the complex formulation of conjugated equine estrogens (Premarin) are protective against neuro-degenerative insults: implications for a composition of estrogen therapy to promote neuronal function and prevent Alzheimer's disease. BMC Neurosci 7:24.