Background: Major depressive disorder (MDD) is a multifactorial chronic and debilitating
mood disease with high lifetime prevalence and associated with excess mortality.
Treatments for this disease are not effective in all patients showing the need to find new therapeutic
Objective: This review aims to update our knowledge on the involvement of astroglial gap junctions
and hemichannels in MDD and to show how they have become potential targets for the
treatment of this pathology.
Methods: The method applied in this review includes a systematic compilation of the relevant
Results and Conclusion: The use of rodent models of depression, gene analysis of hippocampal
tissues of MDD patients and post-mortem studies on the brains from MDD patients suggest that
astrocytic gap junction dysfunction may be a part of MDD etiologies. Chronic antidepressant
treatments of rats, rat cultured cortical astrocytes and human astrocytoma cell lines support the
hypothesis that the up-regulation of gap junctional coupling between astrocytes could be an underlying
mechanism for the therapeutic effect of antidepressants. However, two recent functional
studies suggest that connexin43 hemichannel activity is a part of several antidepressants’
mode of action and that astrocyte gap junctional intercellular communication and hemichannels
exert different effects on antidepressant drug response. Even if they emerge as new therapeutic
targets for new and more active treatments, further studies are needed to decipher the sophisticated
and respective role of astrocytic gap junctions and hemichannels in MDD.