Animal Models of Alcohol Use Disorder: Dose, Sex, and Developmental Differences in Forced and Voluntary Alcohol Consumption

Abstract:

Alcohol use disorder (AUD) is a chronic disorder that is characterized by a reduced ability to inhibit or control the consumption of alcohol, after attempting to minimize or abstain from use. Preclinical studies can model human patterns of the use in monkeys and rodents, most frequently in rats, as in our laboratory. Rats are commonly used because there are strains that escalate drinking (such as Long-Evans rats we use here) and long-term effects of chronic drinking (i.e. from adolescent to adulthood) that can be studied because of their abbreviated lifespan. There are generally two ways that rats are able to consume alcohol; forced and voluntarily. When the rats are forced to consume alcohol the most common techniques are intragastric gavages and vapor chambers. These have the benefit of mimicking large-dose exposure, tolerance, and high blood alcohol content. Other techniques that are not as commonly used are implanted vascular access, intragastric incubation, and intraperitoneal injection. When rats instead voluntarily consume the alcohol, it is typically via the two-bottle access method or a gel matrix. Following a review of the literature on the consumption of alcohol in rats, we discovered that when rats are forced to consume alcohol, they are usually administered 5 g/kg. This dose is dramatically higher than the .5-1.0 g/kg rats usually drink when they have the choice of consuming the alcohol. This ten-fold difference in the doses is due to the investigators, in some cases, aiming to form dependence to alcohol before testing on learning and behavior. We also present what is known about sex differences (males vs. females) and developmental differences (adolescent vs. adult) in animal models of AUD. Overall, the importance of using a preclinical model of AUD is in discovering ways in which to best mimic human use and identifying potential therapeutic interventions.