Modulation by Estrogen-Receptor Directed Drugs of 5-Hydroxytryptamine-2A Receptors in Rat Brain

Cyr, Michel; Landry, Michelle; Paolo, Thérèse Di

doi:10.1016/s0893-133x(00)00085-3

Cited by 97 publications

(54 citation statements)

References 29 publications

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“…Moreover, we reported that tamoxifen, in contrast to estradiol and raloxifene, has no significant modulatory effect on brain serotonin 5-hydroxytryptamine-2A receptors of ovariectomized rats , in most brain regions investigated (Cyr et al 2000b).…”

Section: Nmda Receptors Mrna Levelsmentioning

confidence: 87%

“…We have previously reported that estradiol increases 5-hydroxytryptamine-2A receptor density and expression in rat brain and that raloxifene mimics the effect of estradiol (Cyr et al 2000b). Moreover, we reported that tamoxifen, in contrast to estradiol and raloxifene, has no significant modulatory effect on brain serotonin 5-hydroxytryptamine-2A receptors of ovariectomized rats , in most brain regions investigated (Cyr et al 2000b).…”

Section: Nmda Receptors Mrna Levelsmentioning

confidence: 94%

“…The drug doses were chosen for maximal occupancy of the estrogen receptors and the vehicle was chosen for maximal delivery (Martel et al 1998). Similar drug doses and vehicle were previously used to investigate the effects of estradiol, tamoxifen, and raloxifene on brain 5-HT 2A receptors (Cyr et al 2000b). Treatment began the day after ovariectomy once daily for 14 days; 0.5 ml/rat was injected subcutaneously as suspension, the vehicle consisting of 4% ethanol, 4% polyethylene glycol 600 (PEG-600), 1% gelatin, and 0.9% NaCl in water.…”

Section: Treatmentsmentioning

confidence: 99%

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Estrogen-like Activity of Tamoxifen and Raloxifene on NMDA Receptor Binding and Expression of its Subunits in Rat Brain

Cyr

Thibault

Morissette

et al. 2001

Neuropsychopharmacology

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Hormonal specificity of modulation of N-methyl-D-aspartate (NMDA) receptors was investigated by comparing the effects of estradiol with tamoxifen or raloxifene, which display different responses in breast, bone, and uterus. Two weeks ovariectomy in rats decreasedIt has been shown that the female sex steroid estradiol exerts profound effects on neuronal differentiation during development (Toran-Allerand et al. 1983) and recently, accumulating evidence support also a modulatory role of estrogens in the normal maintenance of brain function during aging (Simpkins et al. 1994). Beneficial effects of estradiol in mood disorders (i.e., depression, pre-menstrual syndrome, post-natal depression), as well as mental diseases, such as schizophrenia and Gille de la Tourette's syndrome, have been reported (Di Paolo 1994;Fink et al. 1998). Moreover, a beneficial role of estradiol in neurodegenerative disFrom the Oncology and Molecular Endocrinology Research Center, Laval University Medical Center, (CHUL), and Faculty of Pharmacy, Laval University, Sainte-Foy, Quebec, Canada, G1V 4G2.Address correspondence to: Dr. Thérèse Di Paolo, Oncology and Molecular Endocrinology Research Center, Laval University Medical Center, CHUQ, 2705, Laurier Boulevard, Sainte-Foy, Quebec, Canada G1V 4G2.Received July 5, 2000; revised December 20, 2000; accepted January 3, 2001. N EUROPSYCHOPHARMACOLOGY 2001 -VOL . 25 , NO . 2 SERMs Modulate NMDA Receptors 243 eases, such as Alzheimer has been recently suggested (Tang et al. 1996;Henderson 1997;Inestrosa et al. 1998). However, the mechanisms by which these effects of estrogens are yet to be fully characterized. N-methyl-D-aspartate (NMDA) receptors, a subtype of ionotropic glutamate receptor, have been implicated, as mediators, in some effects of estradiol on morphological plasticity and related physiological and cognitive processes in the brain (Moriyoshi et al. 1991). However, only few studies have directly investigated the role of estradiol in regulating NMDA receptors in rat and, in addition, these studies have focused on the effects of estradiol on hippocampal NMDA receptors (Woolley and McEwen 1992;Gazzaley et al. 1996;Woolley et al. 1997). We have recently investigated the effects of estradiol on the NMDA receptors agonist sites in brain regions implicated in mental disorders, such as frontal cortex, striatum, and nucleus accumbens (Cyr et al. 2000a). Our experiments showed that ovariectomy, as well as estradiol have regional specific effects since, for example, ovariectomy decreases NMDA receptor specific binding in hippocampal CA1 and dentate gyrus regions, whereas it has no effect in frontal cortex. In contrast, estradiol increases NMDA specific binding in the hippocampal CA1 and the dentate gyrus, but it decreases this binding in the frontal cortex (Cyr et al. 2000a).The present study sought to determine whether changes observed previously at the protein level after hormonal withdrawal due to ovariectomy or after estradiol treatment reflect changes at the level of gene transcription...

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Section: Nmda Receptors Mrna Levelsmentioning

confidence: 87%

Section: Nmda Receptors Mrna Levelsmentioning

confidence: 94%

Section: Treatmentsmentioning

confidence: 99%

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Estrogen-like Activity of Tamoxifen and Raloxifene on NMDA Receptor Binding and Expression of its Subunits in Rat Brain

Cyr

Thibault

Morissette

et al. 2001

Neuropsychopharmacology

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“…Estradiol affects the availability and actions of serotonin by regulating the degradation of monoamine oxidase enzyme 16 and the expression of serotonin transporters, 5HT2A receptors and tryptophan hydroxylase enzyme 5,27 . Raloxifene and estradiol enhance the central serotonergic tone 5,27 , tamoxifen does not 28 and even may block some of the mechanisms involved in the regulation of serotonin uptake by estradiol 29 .…”

Section: Discussionmentioning

confidence: 99%

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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“…Estradiol restores these levels to normal (Cyr et al, 2000b). Therefore, hormone-induced alterations in the serotonergic system cannot be excluded as contributors to the changes in parvalbumin expression seen in the current studies.…”

Section: Limitations and Future Directionsmentioning

confidence: 69%

The Effects of Dopamine and Estrogen upon Cortical Parvalbumin Expression

Ross¹

2001

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Physiology and Genetics, and the Neuroscience ProgramEstrogen plays a protective role in several neurologic disorders known to involve alterations in both the dopamine system and (gamma amino butyric acid containing) GABAergic neurons that contain parvalbumin. Two studies were conducted to identify the effects of estrogen and dopamine upon cortical parvalbumin expression. In the first study, organotypic slice cultures of the frontal cortex were prepared from male rats (postnatal age 2/3) and maintained for 14 days in serum-enriched medium or media containing either: dopamine, estrogen, or a combination of the two. In control slices, parvalbumin immunoreactive neurons were primarily clustered near cortical layer V. All treatment conditions increased the distribution of parvalbumin labeled neurons in layer VI and enhanced the maturation of dendritic measures of labeled neurons in the deep layers (V-VI). Both estrogen and the combination treatment induced similar alterations in the superficial cortical layers, as well. In the second study, gonadectomy (male rats, postnatal age 2) induced long lasting decreased in the density of parvalbumin immunoreactive neurons throughout all cortical layers. Estrogen replacement restored parvalbumin expression to control levels in the superficial cortical layers, only. Gonadectomy also Report Documentation PageForm Public reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. Estrogen plays a protective role in several neurologic disorders known to involve alterations in both the dopamine system and (gamma amino butyric acid containing) GABAergic neurons that contain parvalbumin. Two studies were conducted to identify the effects of estrogen and dopamine upon cortical parvalbumin expression. In the first study, organotypic slice cultures of the frontal cortex were prepared from male rats (postnatal age 2/3) and maintained for 14 days in serum-enriched medium or media containing either: dopamine, estrogen, or a combination of the two. In control slices, parvalbumin immunoreactive neurons were primarily clustered near cortical layer V. All treatment conditions increased the distribution of parvalbumin labeled neurons in layer VI and enhanced the maturation of dendritic measures of labeled neurons in the deep layers (V-VI). Both estrog...

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Modulation by Estrogen-Receptor Directed Drugs of 5-Hydroxytryptamine-2A Receptors in Rat Brain

Abstract: Hormonal specificity of modulation of brain 5-HT

Cited by 97 publications

References 29 publications

Estrogen-like Activity of Tamoxifen and Raloxifene on NMDA Receptor Binding and Expression of its Subunits in Rat Brain

Estrogen-like Activity of Tamoxifen and Raloxifene on NMDA Receptor Binding and Expression of its Subunits in Rat Brain

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

The Effects of Dopamine and Estrogen upon Cortical Parvalbumin Expression

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