Genetic and pharmacological inactivation of astroglial connexin 43 differentially influences the acute response of antidepressant and anxiolytic drugs
| Autor: | Bruno P. Guiard, Renaud Rovera, Sebastien Bullich, Nicole Déglon, Sarah Delcourte, Benjamin Portal, Camille Lejards, Nasser Haddjeri, Cécile E. Malnou |
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| Přispěvatelé: | Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (U1208 Inserm - UCBL1 / SBRI - USC 1361 INRAE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Lausanne University Hospital, Université Paris-Saclay, La Fondation pour la Recherche Médicale' (FRM: DPP20151033959) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Physiology hippocampus 030204 cardiovascular system & hematology Pharmacology connexin 43 MESH: Astrocytes / metabolism Benzodiazepines Mice 0302 clinical medicine MESH: Connexin 43 / genetics [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases MESH: Fluoxetine / pharmacology MESH: Animals Antidepressive Agents 3. Good health serotonin Antidepressant Selective Serotonin Reuptake Inhibitors anxiolytic medicine.drug Elevated plus maze MESH: Benzodiazepines / pharmacology medicine.drug_class Serotonin reuptake inhibitor MESH: Serotonin Uptake Inhibitors / pharmacology MESH: Antidepressive Agents / pharmacology Anxiolytic 03 medical and health sciences MESH: Mice Inbred C57BL Animal models of depression Fluoxetine medicine Animals MESH: Mice Benzodiazepine Diazepam antidepressant MESH: Diazepam / pharmacology business.industry MESH: Connexin 43 / antagonists & inhibitors astrocytes Tail suspension test MESH: Male Mice Inbred C57BL 030104 developmental biology MESH: Astrocytes / drug effects Anti-Anxiety Agents MESH: Anti-Anxiety Agents / pharmacology business |
| Zdroj: | Acta Physiologica Acta Physiologica, Wiley, 2020, 229 (1), pp.e13440. ⟨10.1111/apha.13440⟩ |
| ISSN: | 1748-1708 1748-1716 |
| DOI: | 10.1111/apha.13440⟩ |
| Popis: | International audience; Aim: Astroglial connexins (Cxs) 30 and 43 are engaged in gap junction and hemichannel activities. 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.Methods: To investigate this, we evaluated the behavioural effects of the genetic and pharmacological inactivation of Cx43 on the antidepressant- and anxiolytic-like activities of the selective serotonin reuptake inhibitor fluoxetine and the benzodiazepine diazepam, respectively.Results: A single administration of fluoxetine (18 mg/kg; i.p.) produced a higher increase in hippocampal extracellular serotonin levels, and a greater antidepressant-like effect in the tail suspension test in Cx43 knock-down (KD) mice bred on a C57BL/6 background compared to their wild-type littermates. Similarly, in outbred Swiss wild-type mice, the intra-hippocampal injection of a shRNA-Cx43 or the acute systemic injection of the Cxs inhibitor carbenoxolone (CBX: 10 mg/kg; i.p.) potentiated the antidepressant-like effects of fluoxetine. Evaluating the effects of such strategies on diazepam (0.5 mg/kg; i.p.), the results indicate that Cx43 KD mice or wild-types injected with a shRNA-Cx43 in the amygdala, but not in the hippocampus, attenuated the anxiolytic-like effects of this benzodiazepine in the elevated plus maze. The chronic systemic administration of CBX mimicked the latter observations.Conclusion: Collectively, these data pave the way to the development of potentiating strategies in the field of psychiatry based on the modulation of astroglial Cx43 |
| Databáze: | OpenAIRE |
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