5-HT4 Receptors Are Not Involved in the Effects of Fluoxetine in the Corticosterone Model of Depression
| Autor: | Valérie Compan, Elena Castro, Fuencisla Pilar-Cuéllar, Álvaro Díaz, Emilio Garro-Martínez, Angel Pazos, Josep Amigó, Rebeca Vidal Casado |
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| Přispěvatelé: | Universidad de Cantabria, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Centro de Investigación Biomédica en Red Salud Mental (España) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Physiology Cognitive Neuroscience Hippocampus Anxiety Biochemistry 5-HT4 receptors 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Dorsal raphe nucleus Corticosterone Internal medicine Fluoxetine medicine 030304 developmental biology 0303 health sciences business.industry Depression Dentate gyrus corticosterone fluoxetine Cell Biology General Medicine anxiety Endocrinology chemistry Knockout mouse depression Antidepressant medicine.symptom business 030217 neurology & neurosurgery knockout mice medicine.drug Knockout mice |
| Zdroj: | ACS Chem Neurosci . 2021 Jun 2;12(11):2036-2044 Digital.CSIC. Repositorio Institucional del CSIC instname UCrea Repositorio Abierto de la Universidad de Cantabria Universidad de Cantabria (UC) |
| Popis: | 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]GTPγS 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 naı̈ve 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. 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) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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