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

Abstract

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.

Consumo voluntario de etanol y comportamiento ansioso en Ratas Wistar-Uis

“…Therefore, the interrelation between ethanol consumption and anxiety behaviors leads to the return of uncontrolled consumption of addictive substances. These changes in animal behavior can be generated by the modification of signaling and neurotransmission of structures such as the hippocampus, amygdala, hypothalamic-pituitary axis, mesencephalic structures, and cortex, among others (Dharavath et al, 2023;George et al, 2012;Koob & Volkow, 2016;Marballi et al, 2016;McCool, 2011;Mrejeru et al, 2015;Sanchez-Catalan et al, 2014;Van Skike et al, 2015;Wscieklica et al, 2019). Regarding changes in neurotransmission, studies show modifications in several systems: glutamate, GABA, dopamine, corticotropin-releasing factor, and endocannabinoids, among others (Adermark et al, 2011;Cippitelli et al, 2012;Dharavath et al, 2023;Kim & Souza-Formigoni, 2013;Melis et al, 2009).…”

“…Ethanol changes the release of GABA, dopamine, endogenous opioids, and other neurotransmitters in nuclei of the reward system involved in the hedonic effects of substances of abuse (Dharavath et al, 2023;Ericson et al, 2003;Pautassi et al, 2010). These neuroadaptations cause motivational learning and memory processes that can result in the transition from moderate to excessive ethanol (Dharavath et al, 2023;Ron & Barak, 2016).…”

Unlocking the healing power of psilocybin: an overview of the role of psilocybin therapy in major depressive disorder, obsessive-compulsive disorder and substance use disorder

“…When alcohol consumption is stopped abruptly, the glutamatergic system becomes overly active, which can lead to neuronal hyperactivity and withdrawal symptoms. These symptoms may include anxiety, trembling of the limbs or even seizures in the patient ( 14 ). Therefore, activation of mGlu2 receptors after psilocybin ingestion may help these patients alleviate withdrawal symptoms, reduce cravings for alcohol and limit the occurrence of the harmful phenomenon of excitotoxicity.…”