Antidepressant-Like Effect of Different Estrogenic Compounds in the Forced Swimming Test

Abstract

The present study evaluated the possible antidepressant-like action of the natural estrogen 17b-estradiol (E 2 , 2.5-10 mg/rat), the synthetic steroidal estrogen ethinyl-estradiol (EE 2 , 1.25-10.0 mg/rat), and the nonsteroidal synthetic estrogen, diethyl-stilbestrol (DES, 0.25-1.0 mg/ rat) in ovariectomized adult female Wistar rats using the forced swimming test (FST). The behavioral profile induced by the estrogens was compared with that induced by the antidepressants fluoxetine (FLX, 2.5-10 mg/kg) and desipramine (DMI, 2.5-10 mg/kg). In addition, the temporal course of the antidepressant-like action of the estrogenic compounds was analyzed. FLX and DMI induced an antidepressant-like effect characterized by a reduced immobility and increased swimming for FLX and decreased immobility and increased climbing for DMI. Both E 2 and EE 2 produced a decrease in immobility and an increase in swimming, suggesting an antidepressant-like action. DES did not affect the responses in this animal model of depression at any dose tested. The time course analysis of the actions of E 2 (10 mg/rat) and EE 2 (5 mg/rat) showed that both compounds induced an antidepressant-like effect observed 1 h after their injection lasting for 2-3 days.

Estradiol-Induced Conditioned Place Preference may Require Actions at Estrogen Receptors in the Nucleus Accumbens

“…A similar pattern is observed in animal models. In naturally receptive rats, or OVX rats administered E 2 regimen that produce physiological E 2 levels, anxiety and depression behaviors are decreased (Estrada-Camarena et al, 2003;Frye et al, 2000;Walf, 2002, 2004;Frye and Wawrzycki, 2003;Nomikos and Spyraki, 1988;Rachman et al, 1998;Slater and Blizard, 1976;Frye, 2005a, b, 2006). Thus, these data suggest that E 2 can alter affective responses.…”

Participation of the 5-HT1A Receptor in the Antidepressant-Like Effect of Estrogens in the Forced Swimming Test

“…Using this model (FST), the estrogens 17b-estradiol (E 2 ) and ethynil-estradiol (EE 2 ) have been found to produce antidepressant-like actions (Estrada-Camarena et al, 2003). An important difference between these two estrogens is that the natural estrogen E 2 is more potent at the serotonergic than at the noradrenergic system in decreasing re-uptake sites (Ghraf et al, 1983;Michel et al, 1987), while the synthetic steroidal compound EE 2 inhibits with a comparable efficacy the serotonergic and catecholaminergic sites (Ghraf et al, 1983;Michel et al, 1987).…”

Participation of the Monoaminergic System in the Antidepressant-Like Actions of Estrogens: A Review in Preclinical Studies

“…For example, the administration of estradiol benzoate for 7 or 14 days, induces antidepressant-like effects in the FST (Okada et al, 1997;Rachman et al, 1998). Besides, the antidepressant-like action of estrogenic compounds like 17 -estradiol (E2), 17 -ethinyl-estradiol (EE2) and diarylpropionitrile (DPN, an agonist to estrogen receptors type ) was also observed after an acute treatment (Estrada-Camarena et al, 2003;Walf et al, 2004). Interestingly, a selective estrogen receptor modulator, raloxifene, was only effective after 7 days of treatment; whereas tamoxifen, or the ER agonist, 4,4',4''-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) were ineffective in the FST after an acute or chronic treatment (table 3).…”

“…Studies in monkeys showed that E2 and the selective modulators of estrogen receptors, raloxifene and arzoxifene, increased tryptophan hydroxylase mRNA expression and decreased SERT's mRNA expression Smith et al, 2004). Interestingly, in the FST, raloxifene induced antidepressant-like effects similar to SSRIs such as fluoxetine (Estrada-Camarena et al, 2003;Estrada-Camarena et al, 2010). Studies in rats, analyzing different brain areas, indicate that acute or chronic treatment with estradiol benzoate decreased the number of 3 [H] paroxetine binding sites (Mendelson et al, 1993).…”