Prolame produces anxiolytic- and antidepressant-like effects in middle-aged female rats with less uterotrophic effects than 17β-estradiol.

Autor: Lemini C; Departamento de Farmacología, Facultad de Medicina. Universidad Nacional Autónoma de México. Av. Universidad No. 3000, Ciudad Universitaria, Coyoacán, 04360, Ciudad de México, México., García-Albor E; Laboratorio de Farmacología Conductual, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz. Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, 14370, Ciudad de México, México., Cruz-López B; Laboratorio Integrativo para el Estudio de Sustancias Inhalables Adictivas, Dirección de Investigaciones en Neurociencias. Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz. Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, 14370, Ciudad de México, México., Matamoros-Trejo G; Laboratorio de Neurofisiología Molecular, Dirección de Investigaciones en Neurociencias. Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz. Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, 14370, Ciudad de México, México., Márquez-Baltazar S; Laboratorio de Farmacología Conductual, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz. Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, 14370, Ciudad de México, México., Herrera-Pérez JJ; Laboratorio de Farmacología Conductual, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz. Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, 14370, Ciudad de México, México., Martínez-Mota L; Laboratorio de Farmacología Conductual, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz. Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, 14370, Ciudad de México, México. Electronic address: lucia@imp.edu.mx.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 Apr 15; Vol. 969, pp. 176454. Date of Electronic Publication: 2024 Feb 27.
DOI: 10.1016/j.ejphar.2024.176454
Abstrakt: Estrogen hormone replacement therapy (EHRT), improving women's life quality at menopause, reduces anxiety and depression symptoms associated with ovarian hormonal decline. However, its potential adverse effects, like thromboembolism and cancer risk, limit its use. Prolame is a synthetic 17β-amino estrogen with antithrombotic actions that exerts anxiolytic- and antidepressant-like effects on young adult ovariectomized female rats. It is unknown if prolame's effects may be observed in age and endocrine conditions emulating menopause. This study aimed to identify the antidepressant- and anxiolytic-like effects of prolame and E 2 (used as a reference estrogen treatment) in middle-aged female rats coursing with irregular cycles, in two different conditions: ovariectomized or gonadally intact. Results were compared with those from young adult ovariectomized rats. Prolame (60 or 120 μg/kg), 17β-estradiol (E 2, 40 or 80 μg/kg), or vehicle were chronically administered, and their effects were evaluated in the elevated plus-maze, defensive burying behavior test, open field test, and forced swimming test. Uterotrophic actions were estimated by uterine weight related to body weight. Prolame and E 2 produced robust anxiolytic- and antidepressant-like effects in young adult ovariectomized rats, but these effects were absent in gonadally intact middle-aged rats. Interestingly, only prolame induced anxiolytic- and antidepressant-like effects in middle-aged ovariectomized rats. Uterotrophic effects of prolame were weaker than E 2 effects, notably in middle-aged females. Altogether, present data support the notion that prolame has the potential to be considered an EHRT with relevant psychoactive actions and with apparently lower adverse-side effects, especially in middle-aged populations.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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