Background

Many aspects of alcoholism and alcohol consumption can be studied through animal models. Alcohol induces positive reinforcement, and animals can seek alcohol and even work for it. However, alcohol can also be a negative reinforcement, since it is capable of reducing anxiety. No animal model is able to duplicate the complex features of alcoholism. Oral ethanol self-administration is widely used for examining specific aspects of behavior and physiology relevant for understanding alcoholism (Mardones and Segovia-Riquelme, 1983; Cunningham et al., 2000). Mice can be genetically manipulated at cell type specific levels and therefore are valuable for research into the cell type specific genetic determinants of alcoholism.

The alcohol preference model is one of the most widely used animal models relevant to alcoholism. This model meets important criterion, which is that the ethanol should be self-administered orally (Cicero, 1980; Crabbe et al., 2010). An animal’s genotype exerts a strong influence on self-administration in this model. Some mouse strains, like the inbred strain of mouse C57BL/6J (Rhodes et al., 2005), present a genetically influenced high preference for ethanol and they voluntarily consume it orally (Yoneyama et al., 2008; Barkley-Levenson and Crabbe, 2012). The conditioned place paradigm (CPP) is widely used to explore the effects of addictive substances including alcohol, taking advantage of learned associations. Therefore, alcohol CPP measures the association of alcohol with a particular environment to determine whether mice can acquire alcohol CPP.

Stress can interact with ongoing ethanol consumption to trigger increased intake (e.g., self-medicating behavior), thereby increasing initial susceptibility to alcohol use disorders. Among the stressors, a restraint model of acute and chronic stress can increase ethanol consumption (Yang et al., 2008).

New advances and accumulating evidence support a role for the endocannabinoid system in the effects of alcohol. The endocannabinoid system consists of two cannabinoid receptors, CB1Rs and CB2Rs, with endocannabinoids and the enzymes for the biosynthesis and inactivation of the endocannabinoids. Our goal here was to summarize the protocol used to measure alcohol preference in combination with stress-induced alcohol consumption. We also provide evidence that the endocannabinoid system plays a role in alcohol preference following dopaminergic neuron specific deletion of CB2Rs in the mouse model (Liu et al., 2017).