ABSTRACT
Alcoholic hepatitis (AH) is a unique clinical syndrome on the spectrum of alcohol-associated liver disease (ALD). It constitutes a rising epidemic with increasing incidence and major public health implications. In severe AH, 30-day mortality approaches 30%, yet therapeutic options remain limited. Survival benefit from corticosteroids, the mainstay of medical treatment, is short-lived. Among corticosteroid nonresponders, the use of early liver transplantation is heterogeneous across centers and remains limited by significant barriers. Long-term prognosis is largely dictated by abstinence; however, comorbid alcohol use disorder remains undertreated. Efforts to address these challenges are required to curb the AH epidemic.
Subject(s)
Hepatitis, Alcoholic , Liver Diseases, Alcoholic , Liver Transplantation , Humans , Hepatitis, Alcoholic/diagnosis , Hepatitis, Alcoholic/epidemiology , Hepatitis, Alcoholic/therapy , Liver Diseases, Alcoholic/epidemiology , Prognosis , Alcohol Drinking/epidemiology , Liver Transplantation/adverse effects , Adrenal Cortex Hormones/therapeutic useABSTRACT
To understand the molecular and neural mechanisms underlying alcohol addiction, many models ranging from vertebrates to invertebrates have been developed. In Drosophila melanogaster, behavioral paradigms from assaying acute responses to alcohol and to behaviors more closely modeling addiction have emerged in recent years. However, both the CAFÉ assay, similar to a two-bottle choice consumption assay, as well as conditioned odor preference, where ethanol is used as the reinforcer, are labor intensive and have low throughput. To address this limitation, we have established a novel ethanol consumption preference assay, called FRAPPÉ, which allows for fast, high throughput measurement of consumption in individual flies, using a fluorescence plate reader. We show that naïve flies do not prefer to consume ethanol, but various pre-exposures, such as ethanol vapor or voluntary ethanol consumption, induce ethanol preference. This ethanol-primed preference is long lasting and is not driven by calories contained in ethanol during the consumption choice. Our novel experience-dependent model of ethanol preference in Drosophila-a highly genetically tractable organism-therefore recapitulates salient features of human alcohol abuse and will facilitate the molecular understanding of the development of alcohol preference.
