1. Alcoholism as a global problem of health and study models
Alcohol is a toxic and psychoactive substance that causes dependence and has been consumed as a socially acceptable drug for centuries (World Health Organization, 2018a). In 2016, 43% of the total population (15+ years) was current drinkers and 12.5% were former drinkers. Among drinkers, the record of alcohol per capita consumption was 15.1 liters per year (World Health Organization, 2018b). Alcohol consumption can progress to alcoholism, a condition characterized by a physical dependence on alcohol and the inability to stop or limit drinking (Wood, 2013). Globally, an estimated 237 million men and 46 million women suffer from alcohol use disorders (Härtl and Garwood, 2018). Beyond the significant social and economic losses to individuals and society, the harmful use of alcohol has important health consequences. The impact of alcohol consumption on chronic and acute health outcomes is determined by the total volume of alcohol consumed and the pattern of drinking (World Health Organization, 2018a).
Harmful use of alcohol is accountable for 7.1% and 2.2% of the global burden of disease for males and females, respectively (World Health Organization, 2018a). Twenty-five chronic diseases and conditions are entirely attributable to alcohol, including alcoholic fibrosis and sclerosis of the liver, alcoholic cardiomyopathy, and fetal alcohol syndrome. Additionally, alcohol is a risk component in certain cancers (e.g. mouth cancer, liver cancer, breast cancer, and nasopharynx cancer), mental and behavioral disorders (e.g. unipolar depressive disorders), neurological conditions (e.g. epilepsy), cardiovascular and circulatory diseases (e.g. hypertensive heart disease and ischemic heart disease), brain vascular diseases (e.g. ischemic stroke), and diabetes (Shield et al., 2013; Hendricks, 2020). Of all deaths attributed to alcohol in 2016, 28% were due to injuries, such as those from traffic crashes, self-harm, and interpersonal violence; 21% due to digestive disorders; 19% due to cardiovascular diseases, and the remainder due to infectious diseases, cancers, mental disorders, and other health conditions (Härtl and Garwood, 2018).
Accordingly, alcoholism is a global health problem that requires the study of the molecular and cellular mechanisms that produce different acute and chronic diseases. This can be assessed with animal models. At this respect, the resemblance in the anatomical organization, functional development, and effects of alcohol at the same concentrations (Table 1) between the human and rodent brain compels rodents as a commonly used animal model (Clark and Squire, 2013).
In addition, an accurate model of alcoholism requires the following criteria: a) alcohol must produce positive reinforcing effects, b) the animals must consume the alcohol for its pharmacological effects and not only for its caloric value, taste, or smell, c) the animal should orally self-administer ethanol (EtOH) under free-choice conditions, d) self-administration of EtOH must lead to pharmacologically relevant blood alcohol concentrations, e) the animals should be willing to work to obtain EtOH, f) chronic consumption of EtOH should lead to metabolic and functional tolerance, g) physical signs of withdrawal should develop following EtOH withdrawal after a period of chronic consumption, and h) the animal model easily demonstrates relapse drinking after a prolonged period of abstinence (McBride et al., 2014).
Alcohol models include different methods of ethanol administration like consumption of EtOH in the drinking water (Augier et al., 2014), ethanol-containing liquid diet, vapor inhalation, repeated intraperitoneal injections, intra-gastric infusions of EtOH, schedule-induced EtOH polydipsia, voluntary ethanol drinking paradigm, and food restriction with alcohol as the only fluid available (Crabbe, 2014; Kliethermes, 2005; Tabakoff and Hoffman, 2000). A summary of the principal models is shown in Table 2.