{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T08:55:08Z","timestamp":1780044908598,"version":"3.53.1"},"reference-count":47,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T00:00:00Z","timestamp":1667088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondation pour la Recherche m\u00e9dicale","award":["DPP20151033959"],"award-info":[{"award-number":["DPP20151033959"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Studies suggest that astrocytic connexins (Cx) have an important role in the regulation of high brain functions through their ability to establish fine-tuned communication with neurons within the tripartite synapse. In light of these properties, growing evidence suggests a role of Cx in psychiatric disorders such as major depression but also in the therapeutic activity of antidepressant drugs. However, the real impact of Cx on treatment response and the underlying neurobiological mechanisms remain yet to be clarified. On this ground, the present study was designed to evaluate the functional activity of Cx in a mouse model of depression based on chronic corticosterone exposure and to determine to which extent their pharmacological inactivation influences the antidepressant-like activity of venlafaxine (VENLA). On the one hand, our results indicate that depressed mice have impaired Cx-based gap-junction and hemichannel activities. On the other hand, while VENLA exerts robust antidepressant-like activity in depressed mice; this effect is abolished by the pharmacological inhibition of Cx with carbenoxolone (CBX). Interestingly, the combination of VENLA and CBX is also associated with a higher rate of relapse after treatment withdrawal. To our knowledge, this study is one of the first to develop a model of relapse, and our results reveal that Cx-mediated dynamic neuroglial interactions play a critical role in the efficacy of monoaminergic antidepressant drugs, thus providing new targets for the treatment of depression.<\/jats:p>","DOI":"10.3390\/ijms232113227","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T07:26:50Z","timestamp":1667114810000},"page":"13227","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Astroglial Connexins Inactivation Increases Relapse of Depressive-like Phenotype after Antidepressant Withdrawal"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5648-4169","authenticated-orcid":false,"given":"Benjamin","family":"Portal","sequence":"first","affiliation":[{"name":"Centre de Recherches sur la Cognition Animale, Centre de Biologie Int\u00e9grative, Universit\u00e9 de Toulouse, CNRS, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Vasile","sequence":"additional","affiliation":[{"name":"Neuroglial Interactions in Cerebral Physiopathology, Center for Interdisciplinary Research in Biology, Coll\u00e8ge de France, CNRS UMR 7241, INSERM U1050, Labex Memolife, PSL Research University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Zapata","sequence":"additional","affiliation":[{"name":"Neuroglial Interactions in Cerebral Physiopathology, Center for Interdisciplinary Research in Biology, Coll\u00e8ge de France, CNRS UMR 7241, INSERM U1050, Labex Memolife, PSL Research University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Lejards","sequence":"additional","affiliation":[{"name":"Centre de Recherches sur la Cognition Animale, Centre de Biologie Int\u00e9grative, Universit\u00e9 de Toulouse, CNRS, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6432-1098","authenticated-orcid":false,"given":"Abd El Kader","family":"Ait Tayeb","sequence":"additional","affiliation":[{"name":"CESP, MOODS Team, INSERM, Facult\u00e9 de M\u00e9decine, University of Paris-Saclay, 94275 Le Kremlin Bic\u00eatre, France"},{"name":"Service Hospitalo-Universitaire de Psychiatrie de Bic\u00eatre, H\u00f4pitaux Universitaires Paris-Saclay, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital de Bic\u00eatre, 94275 Le Kremlin Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Colle","sequence":"additional","affiliation":[{"name":"CESP, MOODS Team, INSERM, Facult\u00e9 de M\u00e9decine, University of Paris-Saclay, 94275 Le Kremlin Bic\u00eatre, France"},{"name":"Service Hospitalo-Universitaire de Psychiatrie de Bic\u00eatre, H\u00f4pitaux Universitaires Paris-Saclay, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital de Bic\u00eatre, 94275 Le Kremlin Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8534-224X","authenticated-orcid":false,"given":"C\u00e9line","family":"Verstuyft","sequence":"additional","affiliation":[{"name":"CESP, MOODS Team, INSERM, Facult\u00e9 de M\u00e9decine, University of Paris-Saclay, 94275 Le Kremlin Bic\u00eatre, France"},{"name":"Service de G\u00e9n\u00e9tique Mol\u00e9culaire, Pharmacog\u00e9n\u00e9tique et Hormonologie de Bic\u00eatre, H\u00f4pitaux Universitaires Paris-Saclay, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital de Bic\u00eatre, 94275 Le Kremlin Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Corruble","sequence":"additional","affiliation":[{"name":"CESP, MOODS Team, INSERM, Facult\u00e9 de M\u00e9decine, University of Paris-Saclay, 94275 Le Kremlin Bic\u00eatre, France"},{"name":"Service Hospitalo-Universitaire de Psychiatrie de Bic\u00eatre, H\u00f4pitaux Universitaires Paris-Saclay, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital de Bic\u00eatre, 94275 Le Kremlin Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5574-888X","authenticated-orcid":false,"given":"Nathalie","family":"Rouach","sequence":"additional","affiliation":[{"name":"Neuroglial Interactions in Cerebral Physiopathology, Center for Interdisciplinary Research in Biology, Coll\u00e8ge de France, CNRS UMR 7241, INSERM U1050, Labex Memolife, PSL Research University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6873-9966","authenticated-orcid":false,"given":"Bruno P.","family":"Guiard","sequence":"additional","affiliation":[{"name":"Centre de Recherches sur la Cognition Animale, Centre de Biologie 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