Effects of Long-Term Treatment with Estradiol and Estrogenreceptor Subtype Agonists on Serotonergic Function in Ovariectomized Rats

Saloua Benmansour, Opeyemi S. Adeniji, Anthony A. Privratsky, Alan Frazer

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Acute estradiol treatment was reported to slow the clearance of serotonin via activation of estrogen receptors (ER)β and/or GPR30 and to block the ability of a selective serotonin reuptake inhibitor (SSRI) to slow serotonin clearance via activation of ERα. In this study, the behavioral consequences of longer-term treatments with estradiol or ER subtype-selective agonists and/or an SSRI were examined in the forced swim test (FST). Ovariectomized rats were administered for two weeks: estradiol, ERβ agonist (DPN), GPR30 agonist (G1), ERα agonist (PPT), and/or the SSRI sertraline. Similar to sertraline, longer-term treatment with estradiol, DPN or G1 induced an antidepressant-like effect. By contrast, PPT did not, even though it blocked the antidepressant-like effect of sertraline. Uterus weights, used as a peripheral measure of estrogenic activity, were increased by estradiol and PPT but not DPN or G1 treatment. A second part of this study investigated, using Western blot analyses in homogenates from hippocampus, whether these behavioral effects are accompanied by changes in the activation of specific signaling pathways and/or TrkB. Estradiol and G1 increased phosphorylation of Akt, ERK and TrkB. These effects were similar to those obtained after treatment with sertraline. Treatment with DPN increased phosphorylation of ERK and TrkB but it did not alter that of Akt. Treatment with PPT increased phosphorylation of Akt and ERK without altering that of TrkB. In conclusion, activation of at least TrkB and possibly ERK may be involved in the antidepressant-like effect of estradiol, ERβ and GPR30 agonists whereas Akt activation may not be necessary.

Original languageEnglish (US)
JournalNeuroendocrinology
DOIs
StateAccepted/In press - Jul 1 2015

Fingerprint

Sertraline
Serotonin Receptor Agonists
Estradiol Receptors
NAD
Estradiol
Serotonin Uptake Inhibitors
Estrogen Receptors
Antidepressive Agents
Estrogens
Phosphorylation
Serotonin
Uterus
Hippocampus
Western Blotting
Weights and Measures

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Effects of Long-Term Treatment with Estradiol and Estrogenreceptor Subtype Agonists on Serotonergic Function in Ovariectomized Rats. / Benmansour, Saloua; Adeniji, Opeyemi S.; Privratsky, Anthony A.; Frazer, Alan.

In: Neuroendocrinology, 01.07.2015.

Research output: Contribution to journalArticle

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