Why is alcohol research with nonhuman animals essential?

The following guest post is from Jeff Weiner, a Professor in the Department of Physiology and Pharmacology at Wake Forest School of Medicine.  Dr. Weiner is the Director of an NIH-funded translational research grant that employs rodent, monkey and human models to study the neurobiological substrates that contribute to alcohol addiction vulnerability.  He is also a founding Co-Chair of a new Animal Research and Ethics committee established by the Research Society on Alcoholism.

Jeff Weiner

Jeff Weiner

I am a neuroscientist who directs a translational research program which uses humans, monkeys, and rodents to study  the neurobiological mechanisms associated with increased vulnerability to alcoholism. As an addiction researcher, I am frequently asked why we need to study this topic or why we need to use animal models in our work. I’ve often heard people say that “alcoholism is not really a disease” or that “alcoholics just lack the will to quit drinking”. Others have asked “what can we possibly learn about alcoholism by studying monkeys or rats”?   Well, there are some very good answers to these questions.

First of all, alcoholism is most definitely a disease. While it may be more difficult to diagnose than other illnesses like cancer or diabetes, there is overwhelming evidence, from human and animal studies, that excessive alcohol exposure profoundly changes the brain (and many other organ systems). We now know that alcohol-induced changes in brain activity can last for a very long time, even after the drinking behavior stops, that these neuronal alterations actually make it harder for an addict to quit, and much more likely to relapse when they finally do stop drinking. This research may help to explain why alcohol use disorders affect 5-8% of the US population at a cost to the economy in excess of 180 billion dollars and that alcohol accounts for 4% of the global burden of disease1.

Alcohol consumption USA alcoholism (2)Unlike Huntingon’s disease, alcoholism is not caused by a single gene defect. However, basic research has shown that a complex interaction between our genes and environmental factors, like chronic stress and exposure to traumatic events, can dramatically increase susceptibility to alcohol use disorders. These findings may help to explain why members of our military and their families are disproportionately affected by alcoholism.

Animal research has contributed greatly to the advancement of treatments for alcoholism. Animal models of alcohol use disorders have played an essential role in the discovery of two FDA-approved medications for the treatment of alcohol addiction (naltrexone and acamprosate). In addition, many new pharmacotherapies that have shown promise in animal models are currently being tested in human clinical trials. These new medications may prove even more effective at treating alcohol addiction.

In fact, one recent example illustrates just how powerful animal models of alcohol addiction can be. In 2008, researchers at the Scripps Research Institute in La Jolla, CA used a sophisticated rodent model of alcohol dependence (that they had spent years validating) to show that an FDA-approved anticonvulsant drug called gabapentin might be particularly effective at reducing the escalation in alcohol drinking that occurs after rats have become physically dependent on this drug2. Other researchers at Scripps quickly followed up on these exciting findings and recently completed a carefully controlled, clinical trial testing gabapentin in treatment-seeking alcoholics.   The results of this study, recently published in JAMA Psychiatry, revealed that gabapentin significantly reduced alcohol intake and dependence-associated symptoms like craving, depression, and sleep disturbances3. While much more work needs to be done to confirm these promising initial findings, these studies clearly demonstrate how effective animal models can be in our quest to discover better treatments for this devastating disorder.

It is worth noting that the vast majority of animal research on alcoholism is with rats and mice. Rodents can effectively model many elements of addiction including symptoms of tolerance, dependence, withdrawal, and relapse. Non-human primate models of alcoholism have also proven invaluable in helping to translate discoveries from rodent models to humans.

It is also worth mentioning that all animal research is regulated at multiple levels and by multiple entities. At the federal level the United States Department of Agriculture (USDA) is charged with enforcing the regulations under the Animal Welfare Act (AWA). This Act also requires that animal research be overseen and monitored by local animal care and use committees at the institutional level. Furthermore, research funded by the National Institutes of Health (NIH) must also meet standards for animal care and use as set forth by the Public Health Services (PHS) Policy.

So, while some may still question whether or not alcoholism is really a disease, it seems difficult to argue against the idea that more research is needed to address the huge medical and socio-economic costs associated with alcohol use and abuse. It also seems clear that animal models are a valuable tool that are accelerating the drug discovery process and helping to bring urgently needed treatments to the clinic.

For more information: http://www.niaaa.nih.gov/

References

  1.             Rehm J, Mathers C, Popova S, Thavorncharoensap M, Teerawattananon Y, Patra J. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet. Jun 27 2009;373(9682):2223-2233.
  2.             Roberto M, Gilpin NW, O’Dell LE, et al. Cellular and behavioral interactions of gabapentin with alcohol dependence. J Neurosci. May 28 2008;28(22):5762-5771.
  3.             Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA internal medicine. Jan 2014;174(1):70-77.

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