The Challenge of Studying Parallel Behaviors in Humans and Animal Models

Abstract

The use of animal models is essential in carrying out research into clinical phenomena such as addiction. However, the complexity of the clinical condition inevitably means that even the best animal models are inadequate representations of the condition they seek to mimic. Such mismatches may account for apparent inconsistencies between discoveries in animal models, including the identification of potential novel therapies, and the translation of such discoveries to the clinic. We argue that it is overambitious to attempt to model human disorders such as addiction in animals, and especially in rodents, where "validity" of such models is often limited to superficial similarities, referred to as "face validity" that reflect quite different underlying phenomena and biological processes from the clinical situation. Instead, we suggest a more profitable approach may be to identify (a) well-defined intermediate human behavioral phenotypes that reflect defined, limited aspects of the human clinical disorder, and (b) to develop animal models that are homologous with those discrete human behavioral phenotypes in terms of psychological processes, and underlying neurobiological mechanisms. Examples of current weaknesses and suggestions for more limited approaches that may allow better homology between the test animal and human condition are made.

Sex differences in animal models of psychiatric disorders

“…Animal models are widely used to study the neurobiology of psychiatric disorders and the mechanism of action of current and novel psychotropics (Nestler et al, 2002;Desbonnet et al, 2012). Animal models allowed neuroscience to gain invaluable knowledge, although they have limitations and only simulate specific domains instead of accurately and fully modelling psychiatric syndromes (Neumann et al, 2011;Stephens et al, 2013). However, male animals are routinely used in such preclinical pharmacological studies, as models have been mainly developed and validated for male animals (Beery and Zucker, 2011).…”

Histone-Mediated Epigenetics in Addiction

“…Although significant differences exist between human and animal conditions of drug-craving, seeking, and taking (Stephens et al, 2013), the research field is focused on delineating each aspect of addiction, in hopes of piecing together a pathway for improved treatment and prevention. Because drugs of abuse often change cellular and systemic activity in animals and humans, simple measures of cellular and locomotor sensitization or tolerance are used to measure changes in physiology (e.g., receptor function) and overall behavior after acute or chronic drug administration.…”

Data management strategy for a collaborative research center

“…Projects collecting data from both human and animal models pose several challenges, such as the systematic and parallel implementation of experimental designs, techniques, and analysis tools [ 81 , 82 ]. Data management processes to create harmonized datasets and analysis workflows while establishing clear linkages between human and animal models are difficult, and standards for integrating data are somewhat ad hoc.…”