The effects of raloxifen on depression and cognition in ovariectomized rats

Karahancer, Mehmet; Çırpan, Teksin; Kanıt, Lütfiye; Terek, Mustafa Coşan; Dikmen, Yılmaz; Özşener, Serdar

doi:10.1016/j.fertnstert.2007.02.035

Cited by 8 publications

(8 citation statements)

References 17 publications

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“…CalmarzaFont et al (2012) showed that tamoxifen as well as the other SERMs compound, raloxifene reduced depressive-like behavior induced by stress in ovariectomized mice 22 however, they didn't examine the effects of the drugs in the conditions without stress to compare with the results of present study. Raloxifene has also been reported to decrease depression-like behavior of ovariectomized rats in the FST 23 however, this finding has not been confirmed in other studies 24 and by the results of present study in which tamoxifen was examined. There are also other controversial effects about tamoxifen.…”

Section: Discussioncontrasting

confidence: 96%

Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats

Azizi-Malekabadi

Pourganji

Zabihi

et al. 2015

Arq. Neuro-Psiquiatr.

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The effects of tamoxifen (TAM) on anxiety and depression-like behavior in ovariectomized (OVX) and naïve female rats were investigated. The animals were divided into Sham-TAM, OVX-TAM, Sham and OVX groups. Tamoxifen (1 mg/kg) was administered for 4 weeks. In the forced swimming test, the immobility times in the OVX and Sham-TAM groups were higher than in the Sham group. In the open field, the numbers of central crossings in the OVX and Sham-TAM groups were lower than the number in the Sham group, and the number of peripheral crossings in the OVX group was lower than the number in the Sham group. In the elevated plus maze, the numbers of entries to the open arm among the animals in the Sham-TAM and OVX groups were lower than the number in the Sham group, while the number of entries to the open arm in the OVX-TAM group was higher than the number in the OVX group. It was shown that deletion of ovarian hormones induced anxiety and depression-like behavior. Administration of tamoxifen in naïve rats led to anxiety and depression-like behavior that was comparable with the effects of ovarian hormone deletion. It can be suggested that tamoxifen antagonizes the effects of ovarian hormones. It also seems that tamoxifen has anxiolytic effects on ovariectomized rats.Keywords: rat, ovariectomized, tamoxifen, depression, forced swimming test, open field, elevated plus maze. RESUMOForam investigados os efeitos do tamoxifeno (TAM) no comportamento semelhante a ansiedade de depressão de ratas ooforectomizadas (OVX) e controles. Os animais foram divididos em Sham-TAM, OVX-TAM, Sham e OVX groups. Tamoxifeno (1 mg/kg) foi administrado por quatro semanas. No teste de natação forçada, os tempos de imobilidade nos grupos OVX e Sham-TAM foram maiores que aqueles do grupo Sham. No campo aberto, os números de cruzamento no centro nos grupos OVX e Sham-TAM foram menores que aquele do grupo Sham, e o número dos cruzamentos na periferia no grupo OVX foi menor que o número no grupo Sham. No labirinto elevado, os números de entradas com braços abertos entre os animais nos grupos Sham-TAM e OVX foram menores do que aqueles do grupo Sham, enquanto o número de entradas com os braços abertos no grupo OVX-TAM foi maior que aquele no grupo OVX. Foi observado que a deleção dos hormônios ovarianos induziu comportamento similar a ansiedade e depressão. A administração de tamoxifeno em ratos controle induziu a um comportamento que era comparável aos efeitos da deleção do hormônio ovariano. Pode ser sugerido que o tamoxifeno antagoniza os efeitos dos hormônios ovarianos. Parece também que o tamoxifeno tem efeito ansiolítico nas ratas ooforectomizadas.Palavras-chave: rato, ooforectomia, tamoxifeno, depressão, teste de natação forçada, campo aberto, labirinto elevado.

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Section: Discussioncontrasting

confidence: 96%

Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats

Azizi-Malekabadi

Pourganji

Zabihi

et al. 2015

Arq. Neuro-Psiquiatr.

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“…A limited number of preclinical studies have investigated the effects of SERMs on cognitive function and mood. For example, treatment with tamoxifen or raloxifene improved spatial working memory performance (Karahancer et al, 2008;Lagunas et al, 2011;Velazquez-Zamora et al, 2012), and raloxifene-treated OVX rats had reduced depressivelike (Karahancer et al, 2008) and anxiety-like behaviour (Walf and Frye, 2010). While clinical research investigating the therapeutic benefit of SERMs, particularly raloxifene, in schizophrenia has been and is continuing to be conducted (Wong et al, 2003;Kulkarni et al, 2010;Usall et al, 2011;Huerta-Ramos et al, 2014;Kianimehr et al, 2014), preclinical research is comparatively lacking and therefore the mechanism of action of these compounds remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Comparing the effects of 17β-oestradiol and the selective oestrogen receptor modulators, raloxifene and tamoxifen, on prepulse inhibition in female rats

Gogos

Buuse

2015

Schizophrenia Research

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“…Similar to studies in women (Jarkova et al, 2002; Strickler et al, 2000), raloxifene reduced anxiety-like behavior in the elevated plus maze in a manner congruous to E 2 ; however, there was no effect of this dosing of raloxifene for depression-like behavior in the present study, using the one-trial forced swimming test. Twelve days of daily treatment with raloxifene (1 mg/kg), to Sprague-Dawely rats that were ovariectomized for 21 days before treatment was initiated, showed anti-depressant-like effects in the two-day version of the forced swim test (Karahancer et al, 2008). As described as follows, other studies have demonstrated that raloxifene has modest, or no, effects, compared to E 2 (Berendsen et al, 2001; Gibbs et al, 2004; Karahancer et al, 2008; Pinilla et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…In rats, raloxifene increases potassium-stimulated acetylcholine release (Gibbs et al, 2004), choline acetyltransferase activity (Wu et al, 199), and glutamate AMPA and NMDA receptor binding (Cyr et al, 2001a,b), in the hippocampus. Functionally, raloxifene produces similar taste aversion in young, ovariectomized rats as does tamoxifen (Fudge et al, 2009), and can reduce immobility of rats in a two-day forced swim test (Karahancer et al, 2008). Raloxifene may have neuroprotective effects.…”

Section: Introductionmentioning

confidence: 99%

Raloxifene and/or estradiol decrease anxiety-like and depressive-like behavior, whereas only estradiol increases carcinogen-induced tumorigenesis and uterine proliferation among ovariectomized rats

Walf¹,

Frye²

2010

Behavioural Pharmacology

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Controversy surrounds the efficacy and safety of 17β-estradiol (E 2 )-mimetic therapies to women for treatment of menopausal symptoms. An important question is the nature of the trophic actions of E 2 -mimetics in the brain for behavioral processes versus in the periphery for beneficial effects related to osteoporosis, or unwanted proliferative effects in reproductive tissues, such as mammary glands and uterus. Of recent interest are the effects of selective estrogen receptor modulators (SERMs), which can have tissue specific actions, for these processes. In the present study, the effects was determined of E 2 alone, or co-administered with a SERM, raloxifene, for anxiety-like, depressionlike and trophic peripheral effects in ovariectomized rats that were exposed to a chemical carcinogen (7, 12-dimethylbenz(a)anthracene; DMBA), or not. Once per week, rats were administered vehicle, E 2 (0.09 mg/kg) and/or raloxifene (1 mg/kg) s.c. 44-48 hours before testing in a positive control, E 2 -dependent behavior (lordosis), depression (forced swim test), and anxiety (elevated plus maze) behavioral assays. In addition to behavioral endpoints, incidence and number of tumors, and tumor, pituitary gland, and uterine weight 14 weeks after carcinogen-exposure, and weekly hormone treatments, were analyzed. Rats administered DMBA had increased number and size of tumors, compared to vehicle treatment. E 2 +raloxifene increased the number of tumors. Administration of E 2 or E 2 +raloxifene, but not raloxifene alone, increased pituitary and uterine weight, compared to vehicle administration. E 2 or E 2 +raloxifene, but not raloxifene alone, also increased incidence of lordosis and reduced depression-like behavior in the forced swim test (i.e. decreased time spent immobile) compared to vehicle administration. However, administration of E 2 or raloxifene reduced anxiety behavior in the elevated plus maze (i.e. increased time spent on the open arms of the maze), compared to vehicle. Together these data demonstrate that E 2 and/or raloxifene can have some effects to alter behavior of ovariectomized rodents, depending upon task. As well, E 2 , with or without raloxifene, can also have clear trophic actions in peripheral tissues, such as carcinogen-induced tumors, uterus, and pituitary glands.

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The effects of raloxifen on depression and cognition in ovariectomized rats

Cited by 8 publications

References 17 publications

Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats

Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats

Comparing the effects of 17β-oestradiol and the selective oestrogen receptor modulators, raloxifene and tamoxifen, on prepulse inhibition in female rats

Raloxifene and/or estradiol decrease anxiety-like and depressive-like behavior, whereas only estradiol increases carcinogen-induced tumorigenesis and uterine proliferation among ovariectomized rats

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