ArticlePsychopharmacology2016
17α-ethinyl estradiol attenuates depressive-like behavior through GABAA receptor activation/nitrergic pathway blockade in ovariectomized mice.
Article in Psychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 12 citations in OpenAlex.
- The Impact of Estradiol Dynamics During the Menopause Transition on Depression Risk: A Narrative Review of Estradiol's Neurobiological Mechanisms.Biological psychiatry · 2026Review
- Anti-Inflammatory, Antioxidant, and Neuroprotective Effects of Polyphenols-Polyphenols as an Element of Diet Therapy in Depressive Disorders.International journal of molecular sciences · 2023Review
- Behavioral Despair Is Blocked by the Flavonoid Chrysin (5,7-Dihydroxyflavone) in a Rat Model of Surgical Menopause.Molecules (Basel, Switzerland) · 2023Article
- Sex Differences in Antidepressant Effect of Sertraline in Transgenic Mouse Models.Frontiers in cellular neuroscience · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesThis study was performed to investigate the antidepressant-like effect of 17α-ethinyl estradiol (EE2) in ovariectomized (OVX) mice and the possible role of nitrergic and gamma aminobutyric acid (GABA)ergic pathways in this paradigm.
methodsBilateral ovariectomy was performed in female mice, and different doses of EE2 were intraperitoneally injected either alone or combined with GABAA agonist, diazepam, GABAA antagonist, flumazenil, non-specific nitric oxide synthase (NOS) inhibitor, N(ω)-nitro-L-arginine methyl ester (L-NAME), specific nNOS inhibitor, 7-nitroindazole (7-NI), a nitric oxide (NO) precursor, L-arginine, and selective PDE5I, sildenafil. After locomotion assessment, immobility times were recorded in the forced swimming test (FST) and tail suspension test (TST). Moreover, hippocampal nitrite concentrations were measured in the examined groups.
resultsTen days after ovariectomy, a significant prolonged immobility times were observed. EE2 (0.3 and 1μg/kg and 0.03, 0.1, and 1mg/kg) caused antidepressant-like activity in OVX mice in FST and TST. Diazepam (1 and 5mg/kg), L-NAME (30mg/kg), and 7-NI (100mg/kg) significantly reduced the immobility times. Co-administration of minimal and sub-effective doses of EE2 and diazepam (0.3μg/kg and 0.5mg/kg, respectively) exerted a significant antidepressant-like effect. The same effect was observed in combination of minimal and sub-effective doses of EE2 and either L-NAME or 7-NI. Moreover, combination of minimal and sub-effective doses of EE2, diazepam either L-NAME, or 7-NI emphasized the significant robust antidepressant-like activity.
conclusionsThe study has demonstrated that lowest dose of EE2 exerts a significant antidepressant-like behavior. It is suggested that suppression of NO system, as well as GABAA activation, may be responsible for antidepressant-like activity of EE2 in OVX mice. Moreover, GABAA activation may inhibit nitrergic pathway.
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