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.