Developing neuroscience-based treatments for alcohol addiction: A matter of choice?

Abstract

Excessive alcohol use is the cause of an ongoing public health crisis, and accounts for ~5% of global disease burden. A minority of people with recreational alcohol use develop alcohol addiction (hereafter equated with “alcohol dependence” or simply “alcoholism”), a condition characterized by a systematically biased choice preference for alcohol at the expense of healthy rewards, and continued use despite adverse consequences (“compulsivity”). Alcoholism is arguably the most pressing area of unmet medical needs in psychiatry, with only a small fraction of patients receiving effective, evidence-based treatments. Medications currently approved for the treatment of alcoholism have small effect sizes, and their clinical uptake is negligible. No mechanistically new medications have been approved since 2004, and promising preclinical results have failed to translate into novel treatments. This has contributed to a reemerging debate whether and to what extent alcohol addiction represents a medical condition, or reflects maladaptive choices without an underlying brain pathology. Here, we review this landscape, and discuss the challenges, lessons learned, and opportunities to retool drug development in this important therapeutic area.

Downregulation of Synaptotagmin 1 in the Prelimbic Cortex Drives Alcohol-Associated Behaviors in Rats

“…We previously reported that a history of alcohol dependence results in a persistent downregulation of Syt1 expression in the PL (8). In the present study, we examined whether this effect contributes mechanistically to behaviors characteristic of alcohol addiction (29). In support of this overall hypothesis, we found that a Syt1 KD within the PL increased alcohol selfadministration and the motivation to consume alcohol in nondependent animals, mimicking what is observed following a history of alcohol dependence.…”

Neural network involving medial orbitofrontal cortex and dorsal periaqueductal gray regulation in human alcohol abuse

“…Specifically, rats with deficits in the expression of the γ-aminobutyric acid (GABA) transporter GAT-3 preferred alcohol over a sweet solution, and animals normally preferring the sweet solution switched their preference to alcohol following knockdown of GAT-3. Furthermore, selective reductions in GAT-3 expression in the CeA were also found in people dying with AUD ( 12 ), helping to validate the importance of this murine model.…”

Effective Connectivity in Default Mode Network for Alcoholism Diagnosis

“…A CCORDING to the reports published by the LANCET [1] and NATURE [2], about 5% of global burden of diseases is attributed to excessive alcohol consumption and corresponds to 6% of total deaths that occur annually. Besides, it has been established in [3], that the adverse effects of alcohol far exceed those due to illicit drugs.…”