Large farm animal models of human neurobehavioral and psychiatric disorders: Methodological and practical considerations

Rodents, and in particular murine models, are used in the majority of preclinical animal studies to gain insight into human behavioral dysfunctions, neurological and psychiatric disorders, and to develop therapeutics for the treatment of these disorders. However, many putative new therapeutics turn out to be insufficiently effective in clinical trials, despite their good efficacy and safety in animal models. It is of utmost importance to use appropriate animal models. The brains of gyrencephalic large animal model species, such as (mini)pigs and sheep, for example, show a greater resemblance with the human brain, and might therefore be of larger translational value than rodent models. We review practical and methodological aspects of performing research with large animal models, and discuss their advantages and disadvantages. We advocate to use the animal model that best suits the aim of a study and that best informs the researcher and to consider large animal models as an option.