Salud Mental

Actions of progesterone on depression-like behavior in a model of surgical menopause are mediated by GABAA receptors

##plugins.themes.bootstrap3.article.main##

Abstract

Introduction. In rats, long-term ovariectomy results in low concentrations of steroid hormones and reproduces anxiety- and depression-like behavior after surgical menopause in women. Progesterone produces antidepressant-like effects two weeks post-ovariectomy (i.e., early post-ovariectomy) through actions on γ-aminobutyric acid-A (GABAA) receptors, but its antidepressant-like effects and mechanism of action in rats eight weeks post-ovariectomy (i.e., late post-ovariectomy, considered a model of surgical menopause) remain unknown.

Objective. To explore the antidepressant-like effects of progesterone and the participation of GABAA receptors in rats eight weeks post-ovariectomy.

Method. Long-term ovariectomized female Wistar rats were treated sub-acutely with vehicle or progesterone (.5, 1, and 2 mg/kg) and subjected to the open field and forced swim tests, and behavior was compared with cycling or fluoxetine-treated rats. The rats were then pretreated with picrotoxin (1 mg/kg) followed by progesterone (1 mg/kg) to explore the role of GABAA receptors in long-term-induced depression-like behavior.

Results. Long-term ovariectomized rats exhibited depression-like behavior in the forced swim test compared with intact rats, an effect that was not observed in progesterone- and fluoxetine-treated long-term ovariectomized rats. These effects were not attributable to psychomotor alterations. In the open field test, the time spent rearing and grooming was lower in ovariectomized rats compared with intact rats, which was not observed in progesterone- and fluoxetine-treated rats. Picrotoxin blocked the effects of progesterone in both behavioral tests.

Discussion and conclusion. These results indicated that sub-acute progesterone treatment reduced depression-like behavior through actions on GABAA receptors in a rat model of surgical menopause.
Keywords:
Antidepressant, depression-like behavior, GABAA receptor, picrotoxin, progesterone, surgical menopause

Downloads

Download data is not yet available.

References

Ago, Y., Hasebe, S., Hiramatsu, N., Mori, K., Watabe, Y., Onaka, Y., ... Matsuda, T. (2016). Involvement of GABAA receptor in 5-HT1A and σ1 receptor synergism on prefrontal dopaminergic transmission under circulating neurosteroid deficiency. Psychopharmacology, 233(17), 3125-3134. doi: 10.1007/s00213-016-4353-3

Arbo, B. D., Andrade, S., Osterkamp, G., Gomez, R., & Ribeiro, M. F. (2014). Asymmetric effects of low doses of progesterone on GABA(A) receptor α4 subunit protein expression in the olfactory bulb of female rats. Canadian Journal of Physiology and Pharmacology, 92(12), 1045-1049. doi: 10.1139/cjpp-2014-0307

Baeza, I., de Castro, N. M., Giménez-Llort, L., & de la Fuente, M. (2010). Ovariectomy, a model of menopause in rodents, causes a premature aging of the nervous and immune systems. Journal of Neuroimmunology, 219(1-2), 90-99. doi: 10.1016/j.jneuroim.2009.12.008

Barth, C., Villringer, A., & Sacher, J. (2015). Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods. Frontiers in Neuroscience, 9, 37. doi: 10.3389/fnins.2015.00037

Bossé, R., & Di Paolo, T. (1996). The modulation of brain dopamine and GABAA receptors by estradiol: a clue for CNS changes occurring at menopause. Cellular and Molecular Neurobiology, 16(2), 199-212. doi: 10.1007/BF02088176

Briski, K. P., & Singh, S. R. (2008). Hindbrain neuroglucopenia elicits site-specific transcriptional activation of glutamate decarboxylase-immunopositive neurons in the septopreoptic area of female rat brain. Neuroendocrinology, 87(2), 113-120. doi: 10.1159/000109663

Carver, C. M., & Reddy, D. S. (2013). Neurosteroid interactions with synaptic and extrasynaptic GABAA receptors: regulation of subunit plasticity, phasic and tonic inhibition, and neuronal network excitability. Psychopharmacology, 230(2), 151-188. doi: 10.1007/s00213-013-3276-5

Castagné, V., Porsolt, R. D., & Moser. P. (2009). Use of latency to immobility improves detection of antidepressant-like activity in the behavioral despair test in the mouse. European Journal of Pharmacology, 616(1-3), 128-133. doi: 10.1016/j.ejphar.2009.06.018

Charoenphandhu, J., Teerapornpuntakit, J., Nuntapornsak, A., Krishnamra, N., & Charoenphandhu, N. (2011). Anxiety-like behaviors and expression of SERT and TPH in the dorsal raphé of estrogen- and fluoxetine-treated ovariectomized rats. Pharmacology Biochemistry and Behavior, 98(4), 503-510. doi: 10.1016/j.pbb.2011.02.023

Contreras, C. M., Martínez-Mota, L., & Saavedra, M. (1998). Desipramine restricts estral cycle oscillations in swimming. Progress in Neuro-psychopharmacology and Biological Psychiatry, 22(7), 1121-1128. doi: 10.1016/s0278-5846(98)00066-9

Contreras, C. M., Rodríguez-Landa, J. F., Bernal-Morales, B., Gutiérrez-García A. G., & Saavedra, M. (2011). Timing of progesterone and allopregnanolone effects in a serial forced swim test. Salud Mental, 34(4), 309-314.

Contreras, C. M., Rodríguez-Landa, J. F., Gutiérrez-García, A. G., & Bernal-Morales, B. (2001). The lowest effective dose of fluoxetine in the forced swim test significantly affects the firing rate of lateral septal nucleus neurones in the rat. Journal of Psychopharmacology, 15(4), 231-236. doi: 10.1177/026988110101500401

Daendee, S., Thongsong, B., & Kalandakanond-Thongsong, S. (2013). Effects of time of estrogen deprivation on anxiety-like behavior and GABAA receptor plasticity in ovariectomized rats. Behavioural Brain Research, 246, 86-93. doi: 10.1016/j.bbr.2013.03.008

Das, P., Bell-Horner, C. L., Machu, T. K., & Dillon, G. H (2003). The GABAA receptor antagonist picrotoxin inhibiths 5-hydroxytryptamine type 3A receptors. Neuropharmacology, 44(4), 431-438. doi: 10.1016/S0028-3908(03)00032-7

Diz-Chaves, Y., Kwiatkowska-Naqvi, A., Von Hülst, H., Pernía, O., Carrero, P., & Garcia-Segura, L. M. (2012). Behavioral effects of estradiol therapy in ovariectomized rats depend on the age when the treatment is initiated. Experimental Gerontology, 47(1), 93-99. doi: 10.1016/j.exger.2011.10.008

Erekson, E. A., Martin, D. K., & Ratner, E. S. (2013). Oophorectomy: the debate between ovarian conservation and elective oophorectomy. Menopause, 20(1), 110-114. doi: 10.1097/gme.0b013e31825a27ab

Espejo, E. F., & Miñano, F. J. (1999). Prefrontocortical dopamine depletion induces antidepressant-like effects in rats and alters the profile of desipramine during Porsolt’s test. Neuroscience, 88(2), 609-615. doi: 10.1016/s0306-4522(98)00258-9

Estrada-Camarena, E., Contreras, C. M., Saavedra, M., Luna-Baltazar, I., & López-Ruvalcaba, C. (2002). Participation of the lateral septal nuclei (LSN) in the antidepressant-like actions of progesterone in the forced swimming test (FST). Behavioural Brain Research, 134(1-2), 175-183. doi: 10.1016/s0166-4328(02)00023-2

Estrada-Camarena, E., López-Rubalcava, C., Hernández-Aragón, A., Mejía-Mauries, S., & Picazo, O. (2011). Long-term ovariectomy modulates the antidepressant-like action of estrogens, but not of antidepressants. Journal of Psychopharmacology, 25(10), 1365-1377. doi: 10.1177/0269881111408456

Etter, A., Cully, D. F., Liu, K. K., Reiss, B., Vassilatis, D. K., Schaeffer, J. M., & Arena, J. P. (1999). Picrotoxin blockade of invertebrate glutamate-gate chloride channels: Subunit dependence and evidence for binding within the pore. Journal of Neurochemistry, 72(1), 318-326. doi: 10.1111/jnc.1999.72.1.318

Frye, C. A. (2011a). Progesterone reduces depressive behavior of young ovariectomized, aged progestin receptor knockout, and aged wild type mice in the tail suspension test. Journal of Psychopharmacology, 25(3), 421-428. doi: 10.1177/0269881109349836

Frye, C. A. (2011b). Progesterone attenuates depressive behavior of younger and older adult C57/BL6, wildtype, and progesterone receptor knockout mice. Pharmacology, Biochemistry and Behavior, 99(4), 525-531. doi: 10.1016/j.pbb.2011.05.024

Frye, C. A., & Walf, A. A. (2002). Changes in progesterone metabolites in the hippocampus can modulate open field and forced swim test behavior of proestrous rats. Hormones and Behavior, 41(3), 306-315. doi: 10.1006/hbeh.2002.1763

Frye, C. A., & Walf, A. A. (2004). Hippocampal 3α, 5α-THP may alter depressive behavior of pregnant and lactating rats. Pharmacology, Biochemistry and Behavior, 78(3), 531-540. doi: 10.1016/j.pbb.2004.03.024

Gilad, V. H., Rabey, J. M., Eliyayev, Y., & Gilad, G. M. (2000). Different effects of acute neonatal stressors and long-term postnatal handling on stress-induced changes in behavior and in ornithine decarboxylase activity of adult rats. Developmental Brain Research, 120(2), 255-259. doi: 10.1016/s0165-3806(00)00012-2

Gouveia Jr, A., Antunes, G., Maximino, C., & Morato, S. (2009). The effects of diazepam on the elevated T-maze are dependent on the estrous cycle of rats. Psychology & Neuroscience, 2(2), 227-233. doi: 10.3922/j.psns.2009.2.016

Griffin, L. D., & Mellon, S. H. (1999). Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes. Proceedings of the National Academy of Sciences of the United States of America, 96(23), 13512-13517. doi: 10.1073/pnas.96.23.13512

Guidotti, A. & Costa, E. (1998). Can the antidysphoric and anxiolytic profiles of selective serotonin reuptake inhibitors be related to their ability to increase brain 3α, 5α- tetrahydroprogesterone (allopregnanolone) availability? Biological Psychiatry, 44(9), 865-873. doi: 10.1016/S0006-3223(98)00070-5

Gunn, B. G., Cunningham, L., Mitchell, S. G., Swinny, J. D., Lambert, J. J., & Belelli, D. (2015). GABAA receptor-acting neurosteroids: a role in the development and regulation of the stress response. Frontiers in Neuroendocrinology, 36, 28-48. doi: 10.1016/j.yfrne.2014.06.001

Harlow, S. D., Gass, M., Hall, J. E., Lobo, R., Maki, P., Rebar, R. W., ... de Villiers, T. J. STRAW + 10 Collaborative Group. (2012). Executive summary of the Stages of Reproductive Aging Workshop+ 10: addressing the unfinished agenda of staging reproductive aging. The Journal of Clinical Endocrinology & Metabolism, 97(4), 1159-1168. doi: 10.1210/jc.2011-3362

Hasebe, S., Ago, Y., Watabe, Y., Oka, S., Hiramatsu, N., Tanaka, T., ... Matsuda, T. (2017). Anti-anhedonic effect of selective serotonin reuptake inhibitors with affinity for σ1 receptor in picrotoxin-treated mice. British Journal of Pharmacology, 174(4), 314-327. doi: 10.1111/bph.13692

Herbison, A. E., & Fénelon, V. S. (1995). Estrogen regulation of GABAA receptor subunit mRNA expression in preoptic area and bed nucleus of the stria terminalis of female rat brain. The Journal of Neuroscience, 15(3), 2328-2337. doi: 10.1523/JNEUROSCI.15-03-02328.1995

de Jesús-Burgos, M., Torres-Llenza, V., & Pérez-Acevedo, N. L. (2012). Activation of amygdalar metabotropic glutamate receptors modulates anxiety, and risk assessment behaviors in ovariectomized estradiol-treated female rats. Pharmacology, Biochemistry and Behavior, 101(3), 369-378. doi: 10.1016/j.pbb.2012.01.016

Kalu, D. N. (1991). The ovariectomized rat model of postmenopausal bone loss. Bone Mineral, 15(3), 175-191. doi: 10.1016/0169-6009(91)90124-I

Kalueff, A. V., & Tuohimaa, P. (2005). Contrasting grooming phenotypes in three mouse strains markedly different in anxiety and activity (129S1, BALB/c and NMRI). Behavioural Brain Research, 160(1), 1-10. doi: 10.1016/j.bbr.2004.11.010

Kara, N. Z., Stukalin, Y., & Einat, H. (2018). Revisiting the validity of the mouse forced swim test: Systematic review and meta-analysis of the effects of prototypic antidepressants. Neuroscience & Biobehavioral Reviews, 84, 1-11. doi: 10.1016/j.neubiorev.2017.11.003

Khisti, R. T., Chopde, C. T., & Jain, S. P. (2000). Antidepressant-like effect of the neurosteroid 3α-hydroxy-5α-pregnan-20-one in mice forced swim test. Pharmacology, Biochemistry and Behavior, 67(1), 137-143. doi: 10.1016/s0091-3057(00)00300-2

Kimura, F., Nishihara, M., Hiruma, H., & Funabashi, T. (1991). Naloxone increases the frequency of the electrical activity of luteinizing hormone-releasing hormone pulse generator in long-term ovariectomized rats. Neuroendocrinology, 53(1), 97-102. doi: 10.1159/000125704

Lagunas, N., Calmarza-Font, I., Diz-Chaves, Y., & García-Segura, L. M. (2010). Long-term ovariectomy enhances anxiety and depressive-like behaviors in mice submitted to chronic unpredictable stress. Hormones and Behavior, 58(5), 786-791. doi: 10.1016/j.yhbeh.2010.07.014

Lozano-Hernández, R., Rodríguez-Landa, J. F., Hernández-Figueroa, J. D., Saavedra, M., Ramos-Morales, F. R., & Cruz-Sánchez, S. (2010). Antidepressant-like effects of two commercially available products of Hypericum perforatum in the forced swim test: A long-term study. Journal of Medicinal Plant Research, 4(2), 131-137.

Maki, P. M., Kornstein, S. G., Joffe, H., Bromberger, J. T., Freeman, E. W., Athappilly, G., ... Soares, C. N. (2019). Guidelines for the Evaluation and Treatment of Preimenopausal Depression: Summary and Recommendations. Journal of Women´s Health (Larchmt), 28(2), 117-134. doi: 10.1089/jwh.2018.27099.mensocrec

Martínez-Mota, L., Contreras, C. M., & Saavedra, M. (1999). Progesterone reduces immobility in rats forced to swim. Archives of Medical Research, 30(4), 286-289. doi: 10.1016/S0188-0128(99)00024-X

McGregor, C., Sau, A., Ruddy, S. C., Leung, D., Webb, M., Durst, T., ... Pratt M. C. (2014). Novel ligands balance estrogen receptor β and α agonism for safe and effective suppression of vasomotor response in the ovariectomized female rat of menopause. Endocrinology, 155(7), 2480-2491. doi: 10.1210/en.2013-1976

McLaughlin, K. J., Bimonte-Nelson, H., Neisewander, J. L., & Conrad, C. D. (2008). 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. Hormones and Behavior, 54(3), 386-395. doi: 10.1016/j.yhbeh.2008.04.010

Medina-Maldonado, V., & Eblen-Zajjur, A. (2018). Effects of estradiol or progesterone on principal cells from amygdala complex evaluation in silico. Revista Mexicana de Neuroeciencias, 19(1), 44-55.

Molina, M., Contreras, C. M., & Tellez-Alcantara, P. (1999). Mimosa pudica may possess antidepressant actions in the rat. Phytomedicine, 6(5), 319-323. doi: 10.1016/S0944-7113(99)80052-X

Molina-Hernández, M., Tellez-Alcántara, N. P., Garcı́a, J. P., Lopez, J. O., & Jaramillo, M. T. (2003). Anti-conflict-like actions of intralateral septal infusions of allopregnanolone in Wistar rats. Pharmacology Biochemistry and Behavior, 75(2), 397-404. doi: 10.1016/S0091-3057(03)00133-3

Muttukrishna, S., Sharma, S., Barlow, D. H., Ledger, W., Groome, N., & Sathanandan, M. (2002). Serum inhibins, estradiol, progesterone and FSH in surgical menopause: a demonstration of ovarian pituitary feedback loop in women. Human Reproduction, 17(10), 2535-2539. doi: 10.1093/humrep/17.10.2535

National Research Council. (2011). Guide for the Care and Use of Laboratory Animals: Eighth Edition. Washington DC, USA: The National Academies Press. doi: 10.17226/12910

Nestler, E. J., Gould, E., & Manji, H. (2002). Preclinical models: Status of basic research in depression. Biological Psychiatry, 52(6), 503-528. doi: 10.1016/S0006-3223(02)01405-1

Nin, M. S., Salles, F. B., Azeredo, L. A., Frazon, A. P. G., Gomez, R., Barros, H. M. T. (2008). Antidepressant effect and changes of GABAA receptor γ2 subunit mRNA after hippocampal administration of allopregnanolone in rats. Journal of Psychopharmacology, 22(5), 477-485. doi: 10.1177/0269881107081525

Norma Oficial Mexicana 062-ZOO-1999. (1999). Especificaciones Técnicas para la Producción, Cuidado y Uso de los Animales de Laboratorio. Secretaría de Agricultura, Ganadería, Desarrollo Rural, Pesca y Alimentación, México City. Available on https://www.gob.mx/cms/uploads/attachment/file/203498/NOM-062-ZOO-1999_220801.pdf

Paoletti, A. M., Floris, S., Mannias, M., Orrù, M., Crippa, D., Orlandi, R., ... Melis, G. B. (2001). Evidence that cyproterone acetate improves psychological symptoms and enhances the activity of the dopaminergic system in postmenopause. The Journal of Clinical Endocrinology and Metabolism, 86(2), 608-612. doi: 10.1210/jcem.86.2.7179

Picazo, O., Estrada-Camarena, E., & Hernández-Aragón, A. (2006). Influence of the post-ovariectomy time frame on the experimental anxiety and the behavioural actions of some anxiolytic agents. European Journal of Pharmacology, 530(1-2), 88-94. doi: 10.1016/j.ejphar.2005.11.024

Pinna, G. (2010). In a mouse model relevant for post-traumatic stress disorder, selective brain steroidogenic stimulants (SBSS) improve behavioral deficits by normalizing allopregnanolone biosynthesis. Behavioural Pharmacology, 21(5-6), 438-450. doi: 10.1097/FBP.0b013e32833d8ba0

Pinna, G., Costa, E., & Guidotti, A. (2006). Fluoxetine and norfluoxetine stereospecifically and selectively increase brain neurosteroid content at doses that are inactive on 5-HT reuptake. Psychopharmacology, 186(3), 362-372. doi: 10.1007/s00213-005-0213-2

Porsolt, R. D., Le Pichon, M., & Jalfre, M. L. (1977). Depression: A new animal model sensitive to antidepressant treatments. Nature, 266(5604), 730-702. doi: 10.1038/266730a0

Pribilla, I., Takagi, T., Langosch, D., Bormann, J., & Betz, H. (1992). The atypical M2 segment of β-subunit confers picrotoxinin resistance to inhibitory glycine receptor channels. The EMBO Journal, 11(12), 4305-4311.

Puga-Olguín, A., Rodríguez-Landa, J. F., Rovirosa-Hernández, M. de J., Germán-Ponciano, L. J., Caba, M., Meza, E., ... Olmos-Vázquez, O. J. (2019). Long-term ovariectomy increases anxiety-and despair-like behaviors associated with lower Fos immunoreactivity in the lateral septal nucleus in rats. Behavioural Brain Research, 360, 185-195. doi: 10.1016/j.bbr.2018.12.017

Reddy, D. S. (2018). GABA-A receptors mediate tonic inhibition and neurosteroid sensitivity in the brain. Vitamins and Hormones, 107, 177-191. doi: 10.1016/bs.vh.2017.12.001

Rhodes, M. E., Balestreire, E. M., Czambel, R. K., & Rubin, R. T. (2002). Estrous cycle influences on sexual diergism of HPA axis responses to cholinergic stimulation in rats. Brain Research Bulletin, 59(3), 217-225. doi: 10.1016/S0361-9230(02)00868-7

Rodríguez-Landa, J. F., Contreras, C. M., & García-Ríos, R. I. (2009a). Allopregnanolone microinjected into the lateral septum or dorsal hippocampus reduces immobility in the forced swim test: Participation of the GABAA receptor. Behavioural Pharmacology, 20(7), 614-622. doi: 10.1097/FBP.0b013e328331b9f2

Rodríguez-Landa, J. F., Contreras, C. M., Bernal-Morales, B., Gutiérrez-García, A. G., & Saavedra, M. (2007). Allopregnanolone reduces immobility in the forced swimming test and increases the firing rate of lateral septal neurons through actions on the GABAA receptor in the rat. Journal of Psychopharmacology, 21(1), 76-84. doi: 10.1177/0269881106064203

Rodríguez-Landa, J. F., Cueto-Escobedo, J., Flores-Aguilar, L. Á., Rosas-Sánchez, G. U., Rovirosa-Hernández, M. J., García-Orduña, F., & Carro-Juárez, M. (2018). The aqueous crude extracts of Montanoa frutescens and Montanoa grandiflora reduce immobility faster than fluoxetine through GABAA receptors in rats forced to swim. Journal of Evidence-Based Integrative Medicine, 23, 2515690X18762953. doi: 10.1177/2515690X18762953

Rodríguez-Landa, J. F., Cueto-Escobedo, J., Puga-Olguín, A., Rivadeneyra-Domínguez, E., Bernal-Morales, B., Herrera-Huerta, E. V., Santos-Torres, A. (2017). The phytoestrogen genistein produces similar effects as 17β-estradiol on anxiety-like behavior in rats at 12 weeks after ovariectomy. BioMed Research International, 2017, 9073816. doi: 10.1155/2017/9073816

Rodríguez-Landa, J. F., García-Ríos, R. I., Cueto-Escobedo, J., Bernal-Morales, B., & Contreras, C. M. (2013). Participation of GABAA chloride channel in the anxiolytic-like effects of a fatty acid mixture. Biomed Research International, 2013, 121794. doi: 10.1155/2013/121794

Rodríguez-Landa, J. F., Hernández-Figueroa, J. D., Hernández-Calderón, B. C., & Saavedra, M. (2009b). Anxiolytic-like effect of phytoestrogen genistein in rats with long-term absence of ovarian hormones in the black and white model. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 33(2), 367-372. doi: 10.1016/j.pnpbp.2008.12.024

Rodríguez-Landa, J. F., Hernández-López, F., & Saavedra, M. (2012). Involvement of estrogen receptors in the anxiolytic-like effect of phytoestrogen genistein in rats with 12-week postovariectomy. Pharmacology & Pharmacy, 3(4), 439-446. doi: 10.4236/pp.2012.34059

Rodríguez-Landa, J. F., Rodríguez-Santiago, M. G., Rovirosa-Hernández, M., García-Orduña, F., & Carro-Juárez, M. (2014). Aqueous crude extract of Montanoa tomentosa exerts anxiolytic-like effects in female rats with long-term absence of ovarian hormones. Journal of Chemical, Biological and Physical Sciences, 4(5), 37-46.

Schüle, C., Nothdurfter, C., & Rupprecht, R (2014). The role of allopregnanolone in depression and anxiety. Progress in Neurobiology, 113, 79-87. doi: 10.1016/j.pneurobio.2013.09.003

Smith, S. S., Waterhouse, B. D., Chapin, J. K., & Woodward, D. J. (1987). Progesterone alters GABA and glutamate responsiveness: a possible mechanism for its anxiolytic action. Brain Research, 400(2), 353-359. doi: 10.1016/0006-8993(87)90634-2

Taylor, M. (2001). Psychological consequences of surgical menopause. The Journal of Reproductive Medicine, 46(3 Suppl), 317-324.

Tominaga, K., Yamauchi, A., Shuto, H., Niizeki, M., Makino, K., Oishi, R., & Kataoka, Y. (2001). Ovariectomy aggravates convulsions and hippocampal gamma-aminobutyric acid inhibition induced by cyclosporin A in rats. European Journal of Pharmacology, 430(2-3), 243-249. doi: 10.1016/s0014-2999(01)01377-2

Tonge, S. R., & Greengrass P. M. (1971). The acute effects of oestrogen and progesterone on the monoamine levels of the brain of ovariectomized rats. Psychopharmacologia, 21(4), 374-381. doi: 10.1007/bf02419060

Uzunov, D. P., Cooper, T. B., Costa, E., & Guidotti, A. (1996). Fluoxetine-elicited changes in brain neurosteroid content measured by negative ion mass fragmentography. Proceedings of the National Academy of Sciences, 93(22), 12599-12604. doi: 10.1073/pnas.93.22.12599

Uzunova, V., Sheline, Y., Davis, J. M., Rasmusson, A., Uzunov, D. P., Costa, E., & Guidotti, A. (1998). Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proceedings of the National Academy of Sciences, 95(6), 3239-3244. doi: 10.1073/pnas.95.6.3239

Walf, A. A., Sumida, K., & Frye, C. A. (2006). Inhibiting 5alpha-reductase in the amygdala attenuates antianxiety and antidepressive behavior of naturally receptive and hormone-primed ovariectomized rats. Psychopharmacology, 186(3), 302-311. doi: 10.1007/s00213-005-0100-x

Wronski, T. J., Dann, L. M., Scott, K. S., & Cintrón, M. (1989). Long-term effects of ovariectomy and aging on the rat skeleton. Calcified Tissue International, 45(6), 360-366. doi: 10.1007/bf02556007

Zsakai, A., Karkus, Z., Utczas, K., Biri, B., Sievert, L. L., & Bodzsar, E. B. (2016). Body fatness and endogenous sex hormones in the menopausal transition. Maturitas, 87, 18-26. doi: 10.1016/j.maturitas.2016.02.006