Academic journal article Alcohol Research: Current Reviews

Bridging Animal and Human Models: Translating from (and to) Animal Genetics

Academic journal article Alcohol Research: Current Reviews

Bridging Animal and Human Models: Translating from (and to) Animal Genetics

Article excerpt

Alcoholism is a complex disorder arising from a combination of genetic and environmental factors. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (American Psychiatric Association 1994) requires that three of seven criteria be present during a 12-month period for a diagnosis of alcohol dependence. These criteria are tolerance, withdrawal symptoms, loss of control of drinking, desire to quit, preoccupation with drinking, curtailing of other activities because of drinking, and persistence of drinking in the face of negative consequences. The use of animal models, such as rodents, nonhuman primates, and even invertebrates, allows for a degree of genetic and environmental control that would not be possible in human studies. By using these species to recapitulate discrete aspects of alcohol use disorders (AUDs) as they appear in human populations, researchers are able to target the specific biological underpinnings of the disease.

Achieving consilience between animal models and human disease is one important goal of translational research. Several years ago, a group of researchers staged a multidisciplinary meeting with the goal of identifying specific areas of alcoholism research with good potential for translation between human and animal studies (Crabbe 2010). This effort, known as the consilience project, sought to highlight both better animal models for these areas, as well as better-defined and more specific human phenotypes to target. The group focused on genetic studies because of the obvious direct translation possible across the genomes of species. Currently, animal models clearly are able to address the diagnostic criteria of tolerance and withdrawal but are less obviously capable of capturing complex emotional constructs, such as desire and preoccupation. However, behaviors such as excessive alcohol intake undoubtedly are related to AUDs, despite the fact that they do not directly lead to a diagnosis. By using various animal species to model these other behaviors and risk factors, it is possible to begin to dissect the complexities of alcoholism. After several meetings, members of the consilience project identified seven major areas for focusing translational attention (for the complete report of the consilience group, please see Addiction Biology, 2010, vol. 15, issue 2, entire issue). This article focuses on five of these areas, which encompass specific behavioral domains related to alcohol abuse: withdrawal, reward sensitivity, impulsivity, dysregulated alcohol consumption, and low level of response to alcohol. This article will discuss major findings from both the human and animal literature, as well as some strategies for achieving even better consilience across species in the future.

Genetic Animal Models

Before examining the consilience of animal models and human research, it is important to briefly mention the behavioral genetic strategies used in these types of studies. Although numerous animal species are used in alcohol research, this article will focus primarily on rodent models. However, many of the approaches described here can successfully be applied to other species as well. There are three broad types of genetic methods used in rodent studies of alcohol: testing of inbred strains, selective breeding, and the creation and testing of animals with targeted genetic manipulations.

Inbred mouse and rat strains have been developed over repeated generations through brother-sister matings so that all animals within a strain are assumed to be genetically identical. As a result, these animals provide an excellent means of examining environmental contributions to alcohol-related traits because genetic variation is held constant across subjects. On the other hand, testing animals of multiple strains under standardized environmental conditions can provide evidence for the dependence of a given behavioral phenotype on genetic factors if it is found to differ across strains. …

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