A review on alcohol: from the central action mechanism to chemical dependency

Abstract

Introduction: alcohol is a psychotropic depressant of the central nervous system (CNS) that promotes simultaneous changes in several neuronal pathways, exerting a profound neurological impact that leads to various behavioral and biological alterations. Objectives: to describe the effects of alcohol on the CNS, identifying the signaling pathways that are modified and the biological effects resulting from its consumption. Methods: a literature review was conducted and articles published in different languages over the last 15 years were retrieved. Results: the studies reviewed describe the direct effect of alcohol on several neurotransmitter receptors (gamma-aminobutyric acid [GABA], glutamate, endocannabinoids AEA and 2-AG, among others), the indirect effect of alcohol on the limbic and opioid systems, and the effect on calcium and potassium channels and on proteins regulated by GABA in the hippocampus. Discussion and conclusion: the multiple actions of alcohol on the CNS result in a general effect of psychomotor depression, difficulties in information storage and logical reasoning and motor incoordination, in addition to stimulating the reward system, a fact that may explain the development of addiction. Knowledge on the neuronal signaling pathways that are altered by alcohol allows the identification of effectors which could reduce its central action, thus, offering new therapeutic perspectives for the rehabilitation of alcohol addicts.

An open-label study of sodium oxybate in Spasmodic dysphonia

“…Nevertheless, the observed and reliably reproducible kinetics of the drug's action in the majority of patients may argue against an explanation dependent solely on the placebo benefit. Our current state of knowledge further suggests that the therapeutic benefits from sodium oxybate might not be exclusively placebo driven and likely to be rooted in dystonia pathophysiology because 1) the effects of sodium oxybate were similar to those of alcohol in SD and SD/VT patients; 2) alcohol modulates the inhibitory neurotransmitter GABA; 3) sodium oxybate is structurally similar to GABA, converts into GABA within the brain, and increases the dopamine level mediated by GABA B receptors; and 4) both GABAergic and dopaminergic neurotransmission are abnormally reduced in SD and other dystonias, contributing to the loss of inhibition and abnormal plasticity that and potentially underlying the generation of dystonic movements . Conversion of sodium oxybate into GABA in our patient cohort might have thus directly increased GABA levels and stabilized the balance between excitation and inhibition within the dystonic neural network, leading to the reduction of voice symptoms.…”

Discovery of a Potent, Selective, and Brain-Penetrant Small Molecule that Activates the Orphan Receptor GPR88 and Reduces Alcohol Intake

“…3–6 In regard to the brain reward system, alcohol affects both the dopamine and opioid systems. 4 Accordingly, the competitive opioid antagonist naltrexone and the functional glutamate receptor antagonist acamprosate have been approved by the U.S. Food and Drug Administration to treat alcoholism. 7 However, both drugs face significant challenges including lack of adherence, low efficacy, and serious side effects.…”

Neuropeptide Receptors as Treatment Targets in Alcohol Use Disorders

“…The direct actions of alcohol within the central nervous system (CNS) are poorly understood (39) although mechanisms of action of alcohol via several classical neurotransmitters as well as several neuropeptides have been identified (39). The current number of available pharmacological treatments for AUD is limited to only three to five depending on the country (6).…”