Signaling mechanisms involved in the acute effects of estradiol on 5-HT clearance. (May 2014)

• Record Type: Journal Article
• Authors: Benmansour, Saloua; Privratsky, Anthony A.; Adeniji, Opeyemi S.; Frazer, Alan
• Is Part Of: International journal of neuropsychopharmacology. Volume 17:Number 5(2014)
• Page Start: 765
• Page End: 777
• Publication Date: 2014-05
• Subjects: Neuropsychopharmacology -- Periodicals; Neuropharmacology -- Periodicals; Psychopharmacology -- Periodicals; 615.78
• DOI: 10.1017/S146114571300165X
• Languages: English
• ISSNs: 1461-1457

Abstract

<abstract abstract-type="normal"> <title>Abstract</title> <p>Estradiol was found previously to have an antidepressant-like effect and to block the ability of selective serotonin reuptake inhibitors (SSRIs) to have an antidepressant-like effect. The antidepressant-like effect of estradiol was due to estrogen receptor <italic>β</italic> (ER<italic>β</italic>) and/or GPR30 activation, whereas estradiol's blockade of the effect of an SSRI was mediated by ER<italic>α</italic>. This study focuses on investigating signaling pathways as well as interacting receptors associated with these two effects of estradiol. <italic>In vivo</italic> chronoamperometry was used to measure serotonin transporter (SERT) function. The effect of local application of estradiol or selective agonists for ER<italic>α</italic> (PPT) or ER<italic>β</italic> (DPN) into the CA<sub>3</sub> region of the hippocampus of ovariectomized (OVX) rats on 5-hydroxytryptamine (5-HT) clearance as well as on the ability of fluvoxamine to slow 5-HT clearance was examined after selective blockade of signaling pathways or that of interacting receptors. Estradiol- or DPN-induced slowing of 5-HT clearance mediated by ER<italic>β</italic> was blocked after inhibition of MAPK/ERK1/2 but not of PI3K/Akt signaling pathways. This effect also involved interactions with TrkB, and IGF-1 receptors. Estradiol's or PPT's inhibition of the fluvoxamine-induced slowing of 5-HT clearance mediated by ER<italic>α</italic>, was blocked after inhibition of either MAPK/ERK1/2 or PI3K/Akt signaling pathways. This effect involved interactions with the IGF-1 receptor and with the metabotropic glutamate receptor 1, but not with TrkB. This study illustrates some of the signaling pathways required for the effects of estradiol on SERT function, and particularly shows that ER subtypes elicit different as well as common signaling pathways for their actions.</p> </abstract>