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5-HT4 Receptors Are Not Involved in the Effects of Fluoxetine in the Corticosterone Model of Depression

Identificadores del recurso

1948-7193

SAF2011-25020

SAF2015-67457-R

http://hdl.handle.net/10902/24496

10.1021/acschemneuro.1c00158

Procedencia

(Repositorio Abierto de la Universidad de Cantabria)

Ficha

Título:: 5-HT4 Receptors Are Not Involved in the Effects of Fluoxetine in the Corticosterone Model of Depression
Tema:: corticosterone; 5-HT4 receptors; knockout mice; fluoxetine; anxiety; depression
Descripción:: Clinical and preclinical studies report the implication of 5-hydroxytryptamine 4 receptors (5-HT4Rs) in depression and anxiety. Here, we tested whether the absence of 5-HT4Rs influences the response to the antidepressant fluoxetine in mice subjected to chronic corticosterone administration, an animal model of depression and anxiety. Therefore, the effects of chronic administration of fluoxetine in corticosterone-treated wild-type (WT) and 5-HT4R knockout (KO) mice were evaluated in the open-field and novelty suppressed feeding tests. As 5-HT1A receptor (5-HT1AR) and brain-derived neurotrophic factor (BDNF) are critically involved in depression and anxiety, we further evaluated 5-HT1A receptor functionality by [35S]GTP?S autoradiography and BDNF mRNA expression by in situ hybridization techniques. We found that 5-HT4R KO and WT mice displayed anxiety- and depressive-like behavior following chronic administration of corticosterone, as evidenced in the open-field and novelty suppressed feeding tests. In the open-field, a decreased central activity was observed in na??ve and corticosterone-treated mice of both genotypes following chronic fluoxetine administration. In the novelty suppressed feeding test, a predictive paradigm of antidepressant activity, chronic treatment with fluoxetine reverted the latency to eat in both genotypes. The antidepressant also potentiated the corticosterone-induced desensitization of the 5-HT1AR in the dorsal raphe nucleus. Further, chronic fluoxetine increased BDNF mRNA expression in the dentate gyrus of the hippocampus in corticosterone-treated mice of both genotypes. Therefore, our findings indicate that the behavioral effects of fluoxetine in the corticosterone model of depression and anxiety appear not to be dependent on 5-HT4Rs.; ACKNOWLEDGMENTS: This research was supported by Ministerio de Economía y Competitividad (SAF2011-25020 and SAF2015-67457-R), Ministerio de Ciencia, Innovación y Universidades (RTI2018-097534-B-I00), and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM).
Fuente:: ACS Chem Neurosci . 2021 Jun 2;12(11):2036-2044
Idioma:: English
Relación:: https://doi.org/10.1021/acschemneuro.1c00158
Autor/Productor:: Amigo Riu, Josep; Garro Martínez, Emilio; Vidal Casado, Rebeca; Compan, Valerie; Pilar Cuéllar, María Fuencisla; Pazos Carro, Ángel; Díaz Martínez, Álvaro; Castro Fernández, María Elena
Otros colaboradores/productores:: Universidad de Cantabria
Derechos:: Attribution 4.0 International; © ACS under an ACS AuthorChoice License via Creative Commons BY 4.0; http://creativecommons.org/licenses/by/4.0/; openAccess
Fecha:: 2022-04-04T16:24:38Z; 2021
Tipo de recurso:: info:eu-repo/semantics/article; publishedVersion

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1. <dc:title>5-HT4 Receptors Are Not Involved in the Effects of Fluoxetine in the Corticosterone Model of Depression</dc:title>
2. <dc:creator>Amigo Riu, Josep</dc:creator>
3. <dc:creator>Garro Martínez, Emilio</dc:creator>
4. <dc:creator>Vidal Casado, Rebeca</dc:creator>
5. <dc:creator>Compan, Valerie</dc:creator>
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9. <dc:creator>Castro Fernández, María Elena</dc:creator>
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11. <dc:subject>corticosterone</dc:subject>
12. <dc:subject>5-HT4 receptors</dc:subject>
13. <dc:subject>knockout mice</dc:subject>
14. <dc:subject>fluoxetine</dc:subject>
15. <dc:subject>anxiety</dc:subject>
16. <dc:subject>depression</dc:subject>
17. <dc:description>Clinical and preclinical studies report the implication of 5-hydroxytryptamine 4 receptors (5-HT4Rs) in depression and anxiety. Here, we tested whether the absence of 5-HT4Rs influences the response to the antidepressant fluoxetine in mice subjected to chronic corticosterone administration, an animal model of depression and anxiety. Therefore, the effects of chronic administration of fluoxetine in corticosterone-treated wild-type (WT) and 5-HT4R knockout (KO) mice were evaluated in the open-field and novelty suppressed feeding tests. As 5-HT1A receptor (5-HT1AR) and brain-derived neurotrophic factor (BDNF) are critically involved in depression and anxiety, we further evaluated 5-HT1A receptor functionality by [35S]GTP?S autoradiography and BDNF mRNA expression by in situ hybridization techniques. We found that 5-HT4R KO and WT mice displayed anxiety- and depressive-like behavior following chronic administration of corticosterone, as evidenced in the open-field and novelty suppressed feeding tests. In the open-field, a decreased central activity was observed in na??ve and corticosterone-treated mice of both genotypes following chronic fluoxetine administration. In the novelty suppressed feeding test, a predictive paradigm of antidepressant activity, chronic treatment with fluoxetine reverted the latency to eat in both genotypes. The antidepressant also potentiated the corticosterone-induced desensitization of the 5-HT1AR in the dorsal raphe nucleus. Further, chronic fluoxetine increased BDNF mRNA expression in the dentate gyrus of the hippocampus in corticosterone-treated mice of both genotypes. Therefore, our findings indicate that the behavioral effects of fluoxetine in the corticosterone model of depression and anxiety appear not to be dependent on 5-HT4Rs.</dc:description>
18. <dc:description>ACKNOWLEDGMENTS: This research was supported by Ministerio de Economía y Competitividad (SAF2011-25020 and SAF2015-67457-R), Ministerio de Ciencia, Innovación y Universidades (RTI2018-097534-B-I00), and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM).</dc:description>
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