Mechanisms of Alcohol Addiction: Bridging Human and Animal Studies

John Kramer; Danielle M. Dick; Andrea King; Lara A. Ray; Kenneth J. Sher; Ashley Vena; Leandro F. Vendruscolo; Laura Acion


Alcohol Alcohol. 2020;55(6):603-607. 

In This Article


Bridging human and animal addiction research is highly challenging but also vitally important for assessing theories of addiction etiology. The researchers' different ways of defining what alcohol addiction is (Bickel et al., 2019), and what its critical underlying mechanisms are, have differential implications for its prevention and treatment.

Vendruscolo and colleagues' laboratory approach has helped to parse the somewhat blurry construct of AUD into more meaningful stages and subtypes as well as to facilitate the development and testing of new drug treatments. As a variation on within-subject changes in severity, Ray's typing of problem drinkers based on primary motivation extends a long-standing tradition of alcoholism subtypes. While acknowledging the value of this approach, caution should be exercised in order to avoid reifying the categories, because motives change over time (Littlefield et al., 2010) and may be better viewed as dynamic dimensions rather than stable between-person attributes (Littlefield et al., 2013).

The use of questionnaires and interviews in Ray's and Cho's research to characterize motivation or stage of addiction should be tempered with a recognition of the limits of insight into implicit process and the more general vicissitudes of self-report. As an example, heavy smokers cannot always verbalize a reason for their addiction, because the key underlying processes are elusive and highly automatic. Related to this point, habitual behaviors, which often lack an obvious positive or negative reinforcer, can evolve into addictive, compulsive behaviors. This transition is not currently well understood and might someday be identifiable with the help of biological markers.

Work by King's group highlights the necessity of longitudinal research in evaluating addiction theories such as allostasis and incentive sensitization and understanding individual risk factors for excessive and problematic alcohol use. Although King's CSDP demonstrates that, as groups, heavy and light drinkers experience differing sensitivities to the positive stimulating and rewarding effects of alcohol, individual curves might also be examined to determine the degree of heterogeneity within each group and to indicate whether such individual differences reveal additional important information. While chronological age and time represent valuable ways to chart the course of alcohol effects, individual histories represent another complementary way to distinguish development from course of substance involvement and its correlates.

Finally, Dick's genetic work suggests the complexity and interconnectedness of AUD and one of its key drivers, externalizing behavior. For example, norm-violating behavior and impulsivity precede the onset of addiction, and it might be useful, when estimating the potential for relapse following alcohol treatment, to track not only days abstinent but also changes in these externalizing components. In addition, disinhibited behavior, which is central to externalizing, might differ considerably between individuals; some might exhibit hypersexuality, others anger, aggression or self-destructive behavior, and these differences might have differential implications for substance misuse.

This brief narrative survey—of animal and human addiction research, attendant translational issues and two models that inform these studies—is limited by not being a systematic review. Nevertheless, it is hoped that a case has been made for both the benefits and challenges of combining animal and human approaches to alcohol addiction and, by extension, to other psychiatric conditions. The continuing integration of pre-clinical and clinical work will require both creativity and rigor to ensure that this crosswalk truly improves our care for individuals afflicted by these disorders.