Academic journal article Alcohol Research

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

Academic journal article Alcohol Research

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

Article excerpt

Genetics play an important role in the development and course of alcohol abuse, and understanding genetic contributions to this disorder may lead to improved preventative and therapeutic strategies in the future. Studies both in humans and in animal models are necessary to fully understand the neurobiology of alcoholism from the molecular to the cognitive level. By dissecting the complex facets of alcoholism into discrete, well-defined phenotypes that are measurable in both human populations and animal models of the disease, researchers will be better able to translate findings across species and integrate the knowledge obtained from various disciplines. Some of the key areas of alcoholism research where consilience between human and animal studies is possible are alcohol withdrawal severity, sensitivity to rewards, impulsivity, and dysregulated alcohol consumption. Key words: Alcoholism; alcohol dependence; alcohol use disorders (AUDs); alcohol research; genetic basis of alcoholism; genetics; genetic factors; phenotypes; human studies; animal models; consilience; alcohol withdrawal; alcohol sensitivity; impulsivity; dysregulated alcohol consumption

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, nonhu- man primates, and even invertebrates, allows for a degree of genetic and envi- ronmental 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 phe- notypes 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 preoccu- pation. 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 con- silience 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, dysregu- lated 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. …

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