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Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon 97239, USA
Received August 28, 2012; Accepted August 29, 2012; Published August 31, 2012
Citation: Ryabinin AE (2012) Evolutionary Perspective on Animal Models of Addiction: Diverse Models are Welcome. J Addict Res Ther 3:e113. doi:10.4172/2155-6105.1000e113
Copyright: © 2012 Ryabinin AE. This is an open-access arti cle distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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The slow progress in developing rational therapy of alcoholism and addiction reflects a difficult dilemma: while administering addictive substances to humans creates the risk of increasing their problems, it is extremely difficult to develop an animal model reflecting the complexities of this disorder. This Editorial aims to look at such skeptical view from the perspective of evolutionary biology and claims perhaps an unexpected solution: more evolutionary diverse animal models.
Several excellent reviews on animal models have already been written . In short, they conclude that no serious animal model can reconstruct the complete human phenomenon of addiction or alcoholism. Instead, animal models can successfully reconstruct specific endophenotypes. Most valuable for developing rational pharmacotherapy of addictive behavior are concepts of reliability of an animal model and its predictive validity (Figure 1). In turn, predictive validity can’t be solely based on simple superficial resemblance of the human condition, termed face validity. Instead predictive validity needs to rest on construct validity and/or etiological validity. Construct validity indicates that the same biological mechanisms are involved in the animal model and in the modeled phenomenon. Etiological validity indicates that the cause of the disorder is identical in the model and in humans. It appears logical that the higher evolutionary homology of the modeled phenomenon between humans and the laboratory animal, the more likely the model will have high construct or etiological validity.
For this latter reason it is extremely difficult to model addiction and alcoholism in animal models: no other animal consumes the same highly intoxicating and addictive substances as do humans. Therefore the construct and etiological validity of animal models of addiction and alcoholism can be questioned. No animal besides Homo sapiens has developed distillation technologies. Nevertheless, some predecessors of problematic drinking can be observed in treeshrews and primate species, which consume sufficient amounts of ripe and decaying fruit to experience alcohol intoxication [2,3]. However, 95% of all animal model work in the addiction field is performed in rats and mice. Question arises, if the evolutionary gap between humans and the typical laboratory animals is so large, why has work in mice and rats been successful in predicting effectiveness of several medications used to curb addiction in humans . For example, why are naltrexone and acamprosate largely effective in decreasing excessive alcohol use in mice and in humans?
The explanation includes the evolutionary history of life on Earth. Over the course of evolution there have been several mass extinctions sometimes resulting in extermination of 70% of animal life forms . Therefore, most animal organisms existing today appear to use homologous molecular mechanisms to achieve similar goals. This is why studies in the Aplysia have identified similar molecular mechanisms involved in regulation of memory in these mollusks and in humans . Closer to the addiction field, this is why studies in Drosophila showed that similar molecular mechanisms can be engaged in social stress-induced increases in alcohol drinking in these invertebrates and in mammals . Specifically, these experiments identified that the neuropeptide F, a homologue of the mammalian neuropeptide Y, involved in this behavior. However, these experiments also illustrate the potential problems that could arise from focusing on a single animal model. Since the stress response in vertebrates is regulated in large part by the hypothalamic-pituitary-adrenal (HPA) axis, the HPA is involved in mechanisms regulating stress-induced drinking in mammals. However, this mechanism can’t be involved in this phenomenon in invertebrates, because they lack the HPA axis . Therefore, researchers who would base their research only on studies in Drosophila would definitely miss this important mechanism.
A solution to this problem can be provided by analyses of multiple and taxonomically diverse animal models. If similar mechanisms involved in an addiction-related phenomenon are identified across different species, the probability that the identified mechanisms exist in humans increases. Therefore, multiple animal models provide convergent validity (Figure 1). Moreover, the use of several animal species as models can also provide discriminant validity, as they allow to model different aspects of the addiction-related behaviors.
Recently, discriminant validity has been illustrated by experiments starting to model social aspects of alcoholism and addiction. Previous research in mice and rats successfully modeled many physiological aspects of alcoholism and addiction, whereas the highly social aspects remained rarely modeled. Social aspects of alcoholism and drug addiction are difficult to model even in primates, as the majority of primates studied in laboratories differ from humans in their social structure. In contrast, recent studies in prairie voles, a socially monogamous species, allowed to model peer pressure-like facilitating and “sponsor-like” inhibitory effects of social partners on alcohol drinking [9,10]. These studies lay ground for future successful testing of combined social and pharmacological treatments of alcohol use disorders and addiction, and are an illustration of the need to develop novel animal models.
Many areas in animal models of addiction are unexplored. For example, mollusks have been very successfully used in studies on neurophysiology of learning and memory. Yet, with the exception of few studies , mollusk models of addiction have not been developed. Similarly, birds have been quite successfully used in cognitive neuroscience, yet studies on cognitive effects of drugs of abuse in birds have been largely abandoned . Rather than focusing their animal model on one or two species, addiction researchers should embrace the genetic diversity of animal life and be creative in their approaches to more fully model human disorders.
The author was supported by NIH grants RO1 AA019793, UO1 AA016647 and P60 AA010760 while writing this Editorial.
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