title: The antidepressant-like effect of ethynyl estradiol is mediated by both serotonergic and noradrenergic systems in the forced swimming test.
abstract: 17α-Ethynyl-estradiol (EE2, a synthetic steroidal estrogen) induces antidepressant-like effects in the forced swimming test (FST) similar to those induced by 5-HT and noradrenaline reuptake inhibitors (dual antidepressants). However, the precise mechanism of action of EE2 has not been studied. In the present study, the participation of estrogen receptors (ERs) and the serotonergic and the noradrenergic presynaptic sites in the antidepressant-like action of EE2 was evaluated in the FST. The effects of the ER antagonist ICI 182,780 (10 μg/rat; i.c.v.), the serotonergic and noradrenergic terminal destruction with 5,7-dihydroxytryptamine (5,7-DHT; 200 μg/rat, i.c.v.), and N-(2-chloro-ethyl)-N-ethyl-2-bromobenzylamine (DSP4; 10mg/kg, i.p.) were studied in ovariectomized rats treated with EE2 and subjected to the FST. In addition, the participation of α2-adrenergic receptors in the antidepressant-like action of EE2 was explored using the selective α2-receptor antagonist idazoxan (0.25, 0.5 and 1.0mg/kg, i.p.). EE2 induced an antidepressant-like action characterized by a decrease in immobility behavior with a concomitant increase in swimming and climbing behaviors. The ER antagonist, 5,7-DHT, DSP4, and idazoxan blocked the effects of EE2 on the immobility behavior, whereas ICI 182,780 and 5,7-DHT affected swimming behavior. The noradrenergic compound DSP4 altered climbing behavior, while Idazoxan inhibited the increase of swimming and climbing behaviors induced by EE2. Our results suggest that the antidepressant-like action of EE2 implies a complex mechanism of action on monoaminergic systems and estrogen receptors.
authors.affiliation: Laboratorio de Neuropsicofarmacología, Instituto Nacional de Psiquiatría Ramón de la Fuente, Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, C.P. 14370 México, D.F., Mexico; Departamento de Farmacobiología, Centro de Investigación y Estudios Avanzados-IPN, Calzada de los Tenorios 235, Granjas Coapa, C.P. 14330 México, D.F., Mexico.
authors.forename: N M
authors.initials: NM
authors.lastname: Vega-Rivera
authors.forename: C
authors.initials: C
authors.lastname: López-Rubalcava
authors.forename: E
authors.initials: E
authors.lastname: Estrada-Camarena
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D019329:Idazoxan / Q000494:pharmacology; D007276:Injections, Intraventricular; D009043:Motor Activity / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D013238:Stereotaxic Techniques; D013550:Swimming / Q000523:psychology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000928:Antidepressive Agents; D002395:Catecholamines; D004965:Estrogen Antagonists; D000077267:Fulvestrant; D012701:Serotonin; D004997:Ethinyl Estradiol; D004958:Estradiol; D009638:Norepinephrine; D019329:Idazoxan
keywords: 17α-ethynyl-estradiol; 5,7-DHT; 5,7-dihydroxytryptamine; ANOVA; DA; DSP(4); EDTA; EE(2); ERs; FST; HPLC; N-(2-chloro-ethyl)-N-ethyl-2-bromobenzylamine; NA; OVX; SSRI; analysis of variance; dopamine; estrogen receptors; ethylenediaminetetraacetic acid; ethynyl-estradiol; forced swimming test; high-pressure liquid chromatography; noradrenaline; ovariectomy; presynaptic sites; selective serotonin reuptake inhibitor; serotonin