Heavy-drinking Rodents Enhance Understanding of Problematic Alcohol Use Patterns

New study findings in mice suggest that repeated binge drinking increases the motivation to consume alcohol to excess. In humans, the pattern of drinking (as well as quantity consumed) can be an important indicator of future drink problems; in adolescents, for example, a binge-drinking pattern can predict development of alcohol use disorder (AUD). Studies using laboratory animals that have been selectively bred to drink alcohol (ethanol) in large amounts can provide valuable insights on problematic drinking patterns, using experimental approaches that would be impossible or unethical to apply in humans. Indeed, many important findings on responses to alcohol have been gained from animal studies, conducted to strict welfare guidelines. The latest study, reported in Alcoholism: Clinical and Experimental Research, examined two behaviors in mice that reflect their motivation to experience alcohol’s rewarding effects on the brain.

Two groups of mice bred to be genetically predisposed to drink alcohol excessively, known as ‘high-alcohol-preferring’ (HAP)2 and HAP3, were evaluated. For a 2-hour period over 14 consecutive days, half the mice of each type had access to 20% ethanol, and half to water only (with both fluids provided in specialized bottles that allowed detailed monitoring of the volume consumed). All mice had free access to water at all other times, and to food throughout the study. On day 15, half the mice in each group were provided with the opposite fluid (water in place of ethanol, or vice versa) for the duration of the 2-hour period, while half continued to receive their usual assigned fluid.

The first behavior examined was ‘front-loading’, whereby the rate of consumption of a substance is higher at the onset of access than later on. Both groups of ethanol-assigned mice exhibited front-loading, such that they drank relatively more ethanol in the first 15 minutes than in the remainder of the 2-hour session. Whereas HAP3 mice front-loaded from their first experience of ethanol on day 1, HAP2 mice developed the behavior over several days, which may reflect a progressive increase in motivation to experience alcohol’s rewarding effects.

Second, the researchers assessed how mice reacted to unexpected loss of ethanol access, by measuring consumption after the downshift from the high-reward (ethanol) to lower-reward (water) fluid on day 15. Following a switch to water after two weeks of ethanol access, both HAP2 and HAP3 mice drank less water (and drank it more slowly) than their 2-week water-drinking counterparts. This effect of reduced consumption after an unexpected downshift from a high to lower value reward substance is known as ‘consummatory successive negative contrast’ (cSNC), and supports the relationship between front-loading and the positive motivational effect of ethanol. The cSNC effect has an underlying neurobiology similar to that of addiction, and involves a region of the brain (the central amygdala) that is also implicated in AUD in humans.

There is evidence from both humans and rodents that genetics plays a role in predisposition to binge drinking, and to later development of AUD in humans. In the current study, the observation of cSNC across both HAP2 and HAP3 mice indicates a genetic component to the reaction to loss of alcohol reward, suggesting that there is a biological mechanism that might be targeted. Future research will explore such mechanisms, with the goal of identifying treatments that target people’s motivation to drink alcohol excessively.

High alcohol preferring mice show reaction to loss of ethanol reward following repeated binge drinking. C.E. Ardinger, N.J. Grahame, C.C. Lapish, D.N. Linsenbardt (pages xxx).

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