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Evidence suggests that these functional entities contribute to regulating neurotransmission, thereby influencing brain functions. In particular, preclinical and clinical findings highlight a role of Cx43 in animal models of depression. However, the role of these proteins in response to currently available psychotropic drugs is still unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate this, we evaluated the behavioural effects of the genetic and pharmacological inactivation of Cx43 on the antidepressant\u2010 and anxiolytic\u2010like activities of the selective serotonin reuptake inhibitor fluoxetine and the benzodiazepine diazepam, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A single administration of fluoxetine (18\u00a0mg\/kg; i.p.) produced a higher increase in hippocampal extracellular serotonin levels, and a greater antidepressant\u2010like effect in the tail suspension test in Cx43 knock\u2010down (KD) mice bred on a C57BL\/6 background compared to their wild\u2010type littermates. Similarly, in outbred Swiss wild\u2010type mice, the intra\u2010hippocampal injection of a shRNA\u2010Cx43 or the acute systemic injection of the Cxs inhibitor carbenoxolone (CBX: 10\u00a0mg\/kg; i.p.) potentiated the antidepressant\u2010like effects of fluoxetine. Evaluating the effects of such strategies on diazepam (0.5\u00a0mg\/kg; i.p.), the results indicate that Cx43 KD mice or wild\u2010types injected with a shRNA\u2010Cx43 in the amygdala, but not in the hippocampus, attenuated the anxiolytic\u2010like effects of this benzodiazepine in the elevated plus maze. The chronic systemic administration of CBX mimicked the latter observations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Collectively, these data pave the way to the development of potentiating strategies in the field of psychiatry based on the modulation of astroglial Cx43.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13440","type":"journal-article","created":{"date-parts":[[2020,1,11]],"date-time":"2020-01-11T01:25:48Z","timestamp":1578705948000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Genetic and pharmacological inactivation of astroglial connexin 43 differentially influences the acute response of antidepressant and anxiolytic drugs"],"prefix":"10.1111","volume":"229","author":[{"given":"Benjamin","family":"Portal","sequence":"first","affiliation":[{"name":"Centre de Recherches sur la Cognition Animale (CRCA) Centre de Biologie Int\u00e9grative (CBI) Universit\u00e9 Paul 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