GABAergic signaling in alcohol use disorder and withdrawal: pathological involvement and therapeutic potential

Frontiers in Neural Circuits

Neuroscience

Peter Pangarov¹  Ravinder Naik Dharavath¹  Osnat C. Melamed²  Nikki Bozinoff²  Celeste Pina-Leblanc³  Matthew E. Sloan⁴  Etienne Sibille⁵  Isabelle Boileau⁶  Lena C. Quilty⁷  Thomas D. Prevot⁷  Erica Vieira⁷  Yuliya S. Nikolova⁷  Victor M. Tang⁸  Philip Gerretsen⁹  Daphne Voineskos^1,10  Daniel M. Blumberger^1,10  Anthony C. Ruocco^1,11  Kevin Shield^1,12 

[1] Campbell Family Mental Health Research Institute of CAMH, Toronto, ON, Canada;Campbell Family Mental Health Research Institute of CAMH, Toronto, ON, Canada;Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada;Campbell Family Mental Health Research Institute of CAMH, Toronto, ON, Canada;Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada;Campbell Family Mental Health Research Institute of CAMH, Toronto, ON, Canada;Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada;Addiction Division, CAMH, Toronto, ON, Canada;Division of Neurosciences and Clinical Translation, Department of Psychiatry, University of Toronto, Toronto, ON, Canada;Department of Psychological Clinical Science, University of Toronto Scarborough, Toronto, ON, Canada;Institute of Medical Science, University of Toronto, Toronto, ON, Canada;Institute of Mental Health Policy Research, CAMH, Toronto, ON, Canada;Campbell Family Mental Health Research Institute of CAMH, Toronto, ON, Canada;Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada;Department of Psychiatry, University of Toronto, Toronto, ON, Canada;Campbell Family Mental Health Research Institute of CAMH, Toronto, ON, Canada;Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada;Department of Psychiatry, University of Toronto, Toronto, ON, Canada;Brain Health Imaging Centre, CAMH, Toronto, ON, Canada;Campbell Family Mental Health Research Institute of CAMH, Toronto, ON, Canada;Department of Psychiatry, University of Toronto, Toronto, ON, Canada;Campbell Family Mental Health Research Institute of CAMH, Toronto, ON, Canada;Department of Psychiatry, University of Toronto, Toronto, ON, Canada;Addiction Division, CAMH, Toronto, ON, Canada;Division of Neurosciences and Clinical Translation, Department of Psychiatry, University of Toronto, Toronto, ON, Canada;Institute of Medical Science, University of Toronto, Toronto, ON, Canada;Institute of Mental Health Policy Research, CAMH, Toronto, ON, Canada;Campbell Family Mental Health Research Institute of CAMH, Toronto, ON, Canada;Department of Psychiatry, University of Toronto, Toronto, ON, Canada;Institute of Medical Science, University of Toronto, Toronto, ON, Canada;Brain Health Imaging Centre, CAMH, Toronto, ON, Canada;Campbell Family Mental Health Research Institute of CAMH, Toronto, ON, Canada;Department of Psychiatry, University of Toronto, Toronto, ON, Canada;Temerty Centre for Therapeutic Brain Intervention, CAMH, Toronto, ON, Canada;Campbell Family Mental Health Research Institute of CAMH, Toronto, ON, Canada;Department of Psychiatry, University of Toronto, Toronto, ON, Canada;Temerty Centre for Therapeutic Brain Intervention, CAMH, Toronto, ON, Canada;Department of Psychology, University of Toronto Scarborough, Toronto, ON, Canada;Institute of Mental Health Policy Research, CAMH, Toronto, ON, Canada;

关键词: alcohol use disorders;    clinical trials;    GABA;    integrative approach;    interventions;    pharmacotherapy;    translational;    unmet need;   

DOI  :  10.3389/fncir.2023.1218737

 received in 2023-05-08, accepted in 2023-09-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

Alcohol is one of the most widely used substances. Alcohol use accounts for 5.1% of the global disease burden, contributes substantially to societal and economic costs, and leads to approximately 3 million global deaths yearly. Alcohol use disorder (AUD) includes various drinking behavior patterns that lead to short-term or long-lasting effects on health. Ethanol, the main psychoactive molecule acting in alcoholic beverages, directly impacts the GABAergic system, contributing to GABAergic dysregulations that vary depending on the intensity and duration of alcohol consumption. A small number of interventions have been developed that target the GABAergic system, but there are promising future therapeutic avenues to explore. This review provides an overview of the impact of alcohol on the GABAergic system, the current interventions available for AUD that target the GABAergic system, and the novel interventions being explored that in the future could be included among first-line therapies for the treatment of AUD.

【 授权许可】

Unknown   
Copyright © 2023 Dharavath, Pina-Leblanc, Tang, Sloan, Nikolova, Pangarov, Ruocco, Shield, Voineskos, Blumberger, Boileau, Bozinoff, Gerretsen, Vieira, Melamed, Sibille, Quilty and Prevot.