17β-Estradiol-induced antidepressant-like effect in the Forced Swim Test is absent in estrogen receptor-β knockout (BERKO) mice

Rocha, Beatriz A.; Fleischer, R.; Schaeffer, James M.; Rohrer, Susan P.; Hickey, Gerard J.

doi:10.1007/s00213-004-2078-1

Cited by 175 publications

(133 citation statements)

References 58 publications

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“…Studies utilizing transgenic mice that do not express ERa and/or ERb demonstrate that knockout of these receptors throughout the lifespan have specific behavioral effects. ERb, but not ERa, knockout mice have increased anxiety and depressive behavior compared to their wild type counterparts (Krezel et al, 2001;Imwalle et al, 2005;Rocha et al, 2005;Walf and Frye, 2006a), but their reproductive behavior is intact (Ogawa et al, 1999). On the other hand, ERa knockout mice are infertile and are not sexually receptive when in contact with a sexually experienced male (Ogawa et al, 1998;Ogawa et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…The hippocampus primarily expresses ERb (Shughrue et al, 1997;Shughrue and Merchenthaler, 2001). Studies in ERb knockout mice suggest that ERb is required for affective behavior as these mice have increased anxiety and depression behavior, which is not reversed by E 2 administration (Krezel et al, 2001;Imwalle et al, 2005;Rocha et al, 2005;Walf and Frye, 2006a). Administration of selective ER modulators (SERMs) that have greater affinity for ERb than ERa to ovx rats decrease anxiety and depressive behavior when administered subcutaneously or to the hippocampus Frye, 2005b, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Antisense Oligodeoxynucleotides for Estrogen Receptor-β and α Attenuate Estradiol's Modulation of Affective and Sexual Behavior, Respectively

Walf

Ciriza

Garcia-Segura

et al. 2007

Neuropsychopharmacol

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Estradiol (E 2 ) modulates affective and socio-sexual behavior of female rodents. E 2 's functional effects may involve actions through a and b isoforms of estrogen receptor (ERs). The importance of E 2 's actions at these isoforms for anxiety (open field, elevated plus maze), depression (forced swim test), and sexual behavior (lordosis) was investigated using an antisense oligonucleotide (AS-ODN) strategy. If ERb is required for anti-anxiety and antidepressant-like effects, and ERa is required for sexual receptivity, of E 2 , then intracerebroventricular administration of AS-ODNs against these ERs should attenuate these effects and reduce immunoreactivity of ERs in brain regions that mediate these behaviors, such as the hippocampus and ventral medial hypothalamus (VMH). Ovariectomized rats were primed with 17b-E 2 (10 mg) 48 h before testing (hour 0). At hours 0, 24, and 47.5, rats were infused with saline vehicle, scrambled control AS-ODNs, or AS-ODNs targeted against ERa and/or ERb, and were tested at hour 48. Rats infused with ERb AS-ODNs, alone, or with ERa AS-ODNs had significantly decreased open field central entries, decreased plus maze open arm time and entries, increased time spent immobile, and decreased time spent swimming in the forced swim test, and decreased ERb immunoreactivity in the brain than did rats administered ERa AS-ODNs, vehicle, or scrambled AS-ODNs. Rats that were administered ERa AS-ODNs, alone, or with ERb AS-ODNs had significantly decreased lordosis and decreased ERa immunoreactivity in the brain compared to rats administered ERb AS-ODNs, vehicle, or scrambled AS-ODNs. Thus, ERb and ERa may be required for E 2 's modulation of affective and sexual behavior, respectively.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antisense Oligodeoxynucleotides for Estrogen Receptor-β and α Attenuate Estradiol's Modulation of Affective and Sexual Behavior, Respectively

Walf

Ciriza

Garcia-Segura

et al. 2007

Neuropsychopharmacol

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“…Studies utilizing knockout mice or ERb SERMs suggest that E 2 's actions at ERb may be important for its antianxiety and antidepressant-like effects. ERb knockout mice have increased anxiety (Krezel et al, 2001), and do not have reduced anxiety or depression behavior in response to E 2 administration, as do their wildtype counterparts (Imwalle et al, 2005;Rocha et al, 2005;. S.c. administration of ERb, but not ERa, SERMs decrease anxiety and depressive behavior of OVX rats (Lund et al, 2005;Walf and Frye, 2005b;Walf et al, 2004).…”

Section: Neuropsychopharmacologymentioning

confidence: 97%

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

Walf

Rhodes

Meade

et al. 2006

Neuropsychopharmacol

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Intrinsic rewarding effects of estradiol (E 2 ) may underlie some of the sex differences that emerge postpuberty for the prevalence of drug use and behavioral responses to drugs, but the effects and mechanisms of E 2 for reward have not been well characterized. Conditioned place preference (CPP), as measured by the time spent on the nonpreferred/drug-associated side of the chamber, was utilized as a functional assay to investigate the effects and mechanisms of E 2 in the nucleus accumbens for reward. To determine whether intracellular estrogen receptors (ERs) are important for E 2 -induced CPP, rats were administered E 2 (10 mg; subcutaneously (s.c.)), which produced CPP in each experiment, and/or ER blockers, such as tamoxifen (Experiment 1), ICI 182,780 (Experiment 2), or antisense oligonucleotides targeted to ERs (Experiment 3). Experiment 1: E 2 significantly increased the time spent on the originally nonpreferred side of the chamber. Coadministration of tamoxifen (10 mg/kg; s.c.) attenuated effects of E 2 to produce a CPP, but tamoxifen alone, increased time spent on the nonpreferred side. Experiment 2: coadministration of ICI 182,780 (10 mg/ml) to the nucleus accumbens attenuated effects of E 2 to enhance CPP and did not produce a CPP when administered alone. Experiment 3: coadministration of s.c. E 2 with ER antisense oligonucleotides to the nucleus accumbens significantly decreased time spent on the nonpreferred side and expression of ERs in the nucleus accumbens compared to scrambled antisense oligonucleotides or saline vehicle administration. Thus, E 2 's rewarding effects may involve actions at ERs in the nucleus accumbens.

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“…We selected these genes for two reasons: 1) our prior demonstration of the triggering of affective dysregulation in women with PMDD when exogenous estradiol was administered in the context of GnRH agonist-induced hypogonadism ; 2) recent studies identifying the importance of ER beta in animal models of anxiety and depression (Walf et al 2004;Krezel et al 2001;Rocha et al 2005) and of estrogen receptor alpha in arousal (Garey et al 2003). In addition, we examined associations with the Val158Met SNP (rs4680) in the gene for catechol-O-methyltransferase (COMT), an enzyme involved in estradiol metabolism, implicated in sex hormone-mediated cancer (Tanaka et al 2006;Sazci et al 2004), and observed in other studies to regulate activity in the prefrontal cortex, a brain region implicated as dysfunctional in PMDD (Rubinow et al in press).…”

mentioning

confidence: 99%

Risk for Premenstrual Dysphoric Disorder Is Associated with Genetic Variation in ESR1, the Estrogen Receptor Alpha Gene

Huo

Straub

Roca

et al. 2007

Biological Psychiatry

141

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17β-Estradiol-induced antidepressant-like effect in the Forced Swim Test is absent in estrogen receptor-β knockout (BERKO) mice

Abstract: These data suggest that E2-induced antidepressant-like effects in mice are mediated through activation of ER-beta. They offer preliminary support to the hypothesis that specific compounds acting at ER-beta may influence mood in postmenopausal women.

Cited by 175 publications

References 58 publications

Antisense Oligodeoxynucleotides for Estrogen Receptor-β and α Attenuate Estradiol's Modulation of Affective and Sexual Behavior, Respectively

Antisense Oligodeoxynucleotides for Estrogen Receptor-β and α Attenuate Estradiol's Modulation of Affective and Sexual Behavior, Respectively

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

Risk for Premenstrual Dysphoric Disorder Is Associated with Genetic Variation in ESR1, the Estrogen Receptor Alpha Gene

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