PMID- 31925934
OWN - NLM
STAT- MEDLINE
DCOM- 20210721
LR  - 20221207
IS  - 1748-1716 (Electronic)
IS  - 1748-1708 (Linking)
VI  - 229
IP  - 1
DP  - 2020 May
TI  - Genetic and pharmacological inactivation of astroglial connexin 43 differentially 
      influences the acute response of antidepressant and anxiolytic drugs.
PG  - e13440
LID - 10.1111/apha.13440 [doi]
AB  - 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.
CI  - (c) 2020 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
FAU - Portal, Benjamin
AU  - Portal B
AD  - Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie 
      Integrative (CBI), Universite Paul Sabatier Toulouse III, Toulouse, France.
FAU - Delcourte, Sarah
AU  - Delcourte S
AD  - Univ Lyon, Universite Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research 
      Institute U1208, Bron, France.
FAU - Rovera, Renaud
AU  - Rovera R
AD  - Univ Lyon, Universite Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research 
      Institute U1208, Bron, France.
FAU - Lejards, Camille
AU  - Lejards C
AD  - Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie 
      Integrative (CBI), Universite Paul Sabatier Toulouse III, Toulouse, France.
FAU - Bullich, Sebastien
AU  - Bullich S
AD  - Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie 
      Integrative (CBI), Universite Paul Sabatier Toulouse III, Toulouse, France.
FAU - Malnou, Cecile E
AU  - Malnou CE
AUID- ORCID: 0000-0002-1223-0247
AD  - Centre de Physiopathologie Toulouse-Purpan (CPTP), INSERM, CNRS, Universite de 
      Toulouse, Toulouse, France.
FAU - Haddjeri, Nasser
AU  - Haddjeri N
AUID- ORCID: 0000-0002-2161-2204
AD  - Univ Lyon, Universite Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research 
      Institute U1208, Bron, France.
FAU - Deglon, Nicole
AU  - Deglon N
AUID- ORCID: 0000-0003-4475-9476
AD  - Department of Clinical Neurosciences, Laboratory of Neurotherapies and 
      Neuromodulation (LNTM), Lausanne University Hospital, Lausanne, Switzerland.
AD  - Neuroscience Research Center, LNTM, Lausanne University Hospital, Lausanne, 
      Switzerland.
FAU - Guiard, Bruno P
AU  - Guiard BP
AUID- ORCID: 0000-0002-6873-9966
AD  - Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie 
      Integrative (CBI), Universite Paul Sabatier Toulouse III, Toulouse, France.
AD  - Faculte de Pharmacie, Universite Paris Sud, Universite Paris-Saclay, 
      Chatenay-Malabry, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200116
PL  - England
TA  - Acta Physiol (Oxf)
JT  - Acta physiologica (Oxford, England)
JID - 101262545
RN  - 0 (Anti-Anxiety Agents)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Connexin 43)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 12794-10-4 (Benzodiazepines)
RN  - Q3JTX2Q7TU (Diazepam)
SB  - IM
MH  - Animals
MH  - Anti-Anxiety Agents/*pharmacology
MH  - Antidepressive Agents/*pharmacology
MH  - Astrocytes/*drug effects/metabolism
MH  - Benzodiazepines/pharmacology
MH  - Connexin 43/*antagonists & inhibitors/*genetics
MH  - Diazepam/pharmacology
MH  - Fluoxetine/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Selective Serotonin Reuptake Inhibitors/pharmacology
OTO - NOTNLM
OT  - Connexin 43
OT  - antidepressant
OT  - anxiolytic
OT  - astrocytes
OT  - hippocampus
OT  - serotonin
EDAT- 2020/01/12 06:00
MHDA- 2021/07/22 06:00
CRDT- 2020/01/12 06:00
PHST- 2019/10/01 00:00 [received]
PHST- 2019/12/18 00:00 [revised]
PHST- 2020/01/02 00:00 [accepted]
PHST- 2020/01/12 06:00 [pubmed]
PHST- 2021/07/22 06:00 [medline]
PHST- 2020/01/12 06:00 [entrez]
AID - 10.1111/apha.13440 [doi]
PST - ppublish
SO  - Acta Physiol (Oxf). 2020 May;229(1):e13440. doi: 10.1111/apha.13440. Epub 2020 
      Jan 16.