Effects of two estradiol regimens on anxiety and depressive behaviors and trophic effects in peripheral tissues in a rodent model |
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| Authors: | Alicia A Walf Cheryl A Frye |
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| Institution: | 1. Department of Psychology, The Centers for Neuroscience and Life Sciences Research, The University at Albany-State University of New York, Albany, New York;2. Department of Biological Sciences, The Centers for Neuroscience and Life Sciences Research, The University at Albany-State University of New York, Albany, New York;1. Department of Clinical Sciences, Section for Neurology, Skåne University Hospital, Lund University, Lund, Sweden;2. Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK;3. Positron Emission Tomography Center, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark;4. Department of Experimental Medical Sciences, Wallenberg Neuroscience Center, Lund University, Lund, Sweden;5. Department of Neurology, Central Hospital, Bremerhaven, Germany;6. Neurodegeneration Imaging Group, Department of Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King''s College London, London, UK;1. Dept. of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, United States;2. Neuroscience Program, Tulane University, New Orleans, LA 70118, United States;1. Department of Pharmaceutical Sciences, Health Science Center, Federal University of Espirito Santo, Vitoria, ES 29043-900, Brazil;2. Biochemistry and Pharmacology Postgraduate Program, Health Science Center, Federal University of Espirito Santo, Vitoria, ES 29043-900, Brazil;1. Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, SP, Brazil;2. Department of Speech Language and Hearing Therapy, São Paulo State University, Marília, SP, Brazil;3. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, SP, Brazil;4. Department of Basic Sciences, São Paulo State University Araçatuba, SP, Brazil;1. The Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan;2. School of Computer Science and Technology, Changchun University of Science and Technology, Changchun, China;3. School of Life Science, Beijing Institute of Technology, Beijing, China;4. Department of Radiology, Shengjing Hospital of China Medical University, Liaoning, China;5. College of Computer Science and Technology, Taiyuan University of Technology, Taiyuan, China |
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| Abstract: | Background: With aging and menopause, which are associated with decreases in ovarian steroids such as 17β-estradiol (E2), women might experience negative psychological symptoms, including anxiety and depression. Some women use E2-based therapies to alleviate these symptoms, but E2 has been associated with trophic effects that might increase vulnerability to some steroid-sensitive cancers, such as breast cancer, in both premenopausal and postmenopausal women.Objective: This study investigated the relationships between the possible beneficial effects of E2 on anxiety and depressive behaviors concurrent with trophic effects using an animal model of E2 decline and replacement.Methods: Dose-dependent effects of E2 on affective, sexual, and motor behavior of young adult rats were studied. Ovariectomized (OVX) rats were administered the chemical carcinogen 7,12-dimethylbenz(a) anthracene (DMBA) 1.25 mg or inactive vehicle (vegetable oil; control) by gavage. E2 (0.03 or 0.09 mg/kg) or vehicle was administered subcutaneously 44 to 48 hours before assessments of anxiety (light—dark transition), depression (forced swim test), sexual (lordosis), and motor (activity monitor) behaviors. Fourteen weeks after carcinogen exposure, E2 concentrations in plasma and brain regions (cortex, hippocampus, and hypothalamus) were determined. Incidences and numbers of tumors and uterine weight were analyzed.Results: Administration of E2 (0.09 mg/kg) was associated with significant increases in antianxiety-like behavior in the light—dark transition task, antidepressant-like behavior in the forced swim test, and physiologic circulating and central E2 concentrations compared with E2 (0.03 mg/kg) and vehicle. Compared with vehicle, E2 (0.9 > 0.3 mg/kg) was associated with significant increases in lordosis and uterine weight. Administration of DMBA was associated with significant increases in the incidences and numbers of tumors; this effect was augmented by E2administration.Conclusions: Based on the findings in this rat model, the hypothesis that E2 may be effective in reducing anxiety and depressive behaviors and enhance sexual behavior in OVX rats, concurrent with trophic effects in the periphery, was supported. Moderate physiologic levels of E2 might have beneficial effects on affective and sexual behaviors in female rodents, but regimens including E2 might increase tumorigenic capacity. |
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