Combined fluoxetine and metformin treatment potentiates antidepressant efficacy increasing IGF2 expression in the dorsal hippocampus
| العنوان: | Combined fluoxetine and metformin treatment potentiates antidepressant efficacy increasing IGF2 expression in the dorsal hippocampus |
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| المؤلفون: | Laura Maggi, Giampaolo Milior, Silvia Alboni, Gloria Matte Bon, S. Poggini, Livio Pepe’ Sciarria, Stefano Puglisi-Allegra, Cristina Limatola, Nicoletta Brunello, Igor Branchi, A. Viglione, M.T. Golia |
| المساهمون: | Istituto Superiore di Sanita [Rome], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Università degli Studi di Modena e Reggio Emilia, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Scuola Normale Superiore di Pisa (SNS), Fondazione Santa Lucia [IRCCS], Clinical and Behavioral Neurology [IRCCS Santa Lucia], Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Gestionnaire, Hal Sorbonne Université, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Neural plasticity Neural plasticity, Hindawi Publishing Corporation, 2019, 2019, pp.4651031. ⟨10.1155/2019/4651031⟩ Neural Plasticity, Vol 2019 (2019) Neural plasticity, 2019, 2019, pp.4651031. ⟨10.1155/2019/4651031⟩ Neural Plasticity |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Anhedonia, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Hippocampus, Pharmacology, Mice, 0302 clinical medicine, 0303 health sciences, Long-term potentiation, anhedonia, animals, antidepressive agents, depressive disorder, disease models, animal, drug therapy, combination, fluoxetine, hippocampus, hypoglycemic agents, insulin-like growth factor II, male, metformin, mice, serotonin uptake inhibitors, Antidepressive Agents, Metformin, 3. Good health, Neurology, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Combination, Serotonin Uptake Inhibitors, Antidepressant, Major depressive disorder, Drug Therapy, Combination, medicine.symptom, Selective Serotonin Reuptake Inhibitors, medicine.drug, Research Article, Article Subject, lcsh:RC321-571, 03 medical and health sciences, Drug Therapy, Insulin-Like Growth Factor II, Fluoxetine, medicine, Animals, Hypoglycemic Agents, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, 030304 developmental biology, Depressive Disorder, business.industry, Animal, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, Disease Models, Animal, Mood, Disease Models, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Neurology (clinical), business, 030217 neurology & neurosurgery |
| الوصف: | International audience; An increasing number of studies show that selective serotonin reuptake inhibitors (SSRIs) exert their therapeutic action, at least in part, by amplifying the influence of the living environment on mood. As a consequence, when administered in a favorable environment, SSRIs lead to a reduction of symptoms, but in stressful conditions, they show limited efficacy. Therefore, novel therapeutic approaches able to neutralize the influence of the stressful environment on treatment are needed. The aim of our study was to test whether, in a mouse model of depression, the combined administration of SSRI fluoxetine and metformin, a drug able to improve the metabolic profile, counteracts the limited efficacy of fluoxetine alone when administered in stressful conditions. Indeed, metabolic alterations are associated to both the onset of major depression and the antidepressant efficacy. To this goal, adult C57BL/6 male mice were exposed to stress for 6 weeks; the first two weeks was aimed at generating a mouse model of depression. During the remaining 4 weeks, mice received one of the following treatments: vehicle, fluoxetine, metformin, or a combination of fluoxetine and metformin. We measured liking- and wanting-type anhedonia as behavioral phenotypes of depression and assessed the expression levels of selected genes involved in major depressive disorder and antidepressant response in the dorsal and ventral hippocampus, which are differently involved in the depressive symptomatology. The combined treatment was more effective than fluoxetine alone in ameliorating the depressive phenotype after one week of treatment. This was associated to an increase in IGF2 mRNA expression and enhanced long-term potentiation, specifically in the dorsal hippocampus, at the end of treatment. Overall, the present results show that, when administered in stressful conditions, the combined fluoxetine and metformin treatment may represent a more effective approach than fluoxetine alone in a short term. Finally, our findings highlight the relevance of polypharmacological strategy as effective interventions to increase the efficacy of the antidepressant drugs currently available. |
| وصف الملف: | application/pdf; text/xhtml |
| اللغة: | English |
| تدمد: | 2090-5904 1687-5443 |
| DOI: | 10.1155/2019/4651031⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::85afcf2bc0f10a2f2ae480f960de281c https://hdl.handle.net/11380/1201694 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....85afcf2bc0f10a2f2ae480f960de281c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20905904 16875443 |
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| DOI: | 10.1155/2019/4651031⟩ |