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Front. Psychiatry | doi: 10.3389/fpsyt.2019.00580

Targeting the glucocorticoid receptors during alcohol-withdrawal to reduce protracted neurocognitive disorders

  • 1Centre National de la Recherche Scientifique (CNRS), France

Persistent regional glucocorticoids (GCs) dysregulation in alcohol-withdrawn subjects emerges as a key factor responsible for protracted molecular and neural alterations associated with long-term cognitive dysfunction. The demonstration that regional brain concentrations of corticosterone can change in alcohol withdrawn subjects independently from plasma concentrations may have important implications for the treatment of alcohol withdrawal-induced persistent pathology. Thus, from a pharmacological point of view, a main issue remains to determine the relative efficacy of compounds targeting the GCs receptors to attenuate or suppress the long-lasting persistence of brain regional GCs dysfunctions in abstinent alcoholics, as well as persistent changes of neural plasticity. Data from animal research show that acting directly on GCs receptors during the withdrawal period, via selective antagonists, can significantly counteract the development and persistence of cognitive and neural plasticity disorders during protracted abstinence. A critical remaining issue is to better assess the relative long-term efficacy of GC antagonists and other compounds targeting the corticotropic axis activity such as GABAA and GABAB agonists. Indeed, benzodiazepines (acting indirectly on GABAA receptors) and baclofen (agonist of the GABAB receptor) are the compounds the most widely used to reduce alcohol dependence. Clinical and preclinical data suggest that baclofen exerts an effective and more powerful counteracting action on such persistent cognitive and endocrine dysfunctions as compared to diazepam, even though its potential negative effects on memory processes particularly at high doses should be better taken into account.

Keywords: Alcohol withdrawal, Baclofen, Benzodiazepines (BDZ), Corticosterone (CORT), GABA, Glucocorticoids (GCs), Prefrontal Cortex, Working Memory - Long-term Memory Interactions

Received: 21 Dec 2018; Accepted: 23 Jul 2019.

Edited by:

Renaud De Beaurepaire, Groupe hospitalier Paul Guiraud (GHPG), France

Reviewed by:

Gabriel Rubio, University Hospital October 12, Spain
Verica Milivojevic, School of Medicine, Yale University, United States  

Copyright: © 2019 David, Mons and Beracochea. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Vincent David, Centre National de la Recherche Scientifique (CNRS), Paris, 33405, France, vincent.david@u-bordeaux.fr
PhD. Daniel Beracochea, Centre National de la Recherche Scientifique (CNRS), Paris, 33405, France, daniel.berachochea@u-bordeaux.fr