Utility And Limitations

Most animal models used to study aspects of depression in humans have utilized males, but the prevalence of depression in humans is nearly two times higher in women than in men (Shively et al. 2005). Another limitation of animal models is the tendency to focus on single factors as the cause of depression in humans (Willner 1990). In certain cases, one causal factor may be identified, but more often than not, depression evolves from a nexus of causal risk factors that accumulate over the life span (Kendler et al. 2002). Attempts to model aspects of depression in animals based on one causal factor may be impractical if no single factor is sufficiently potent to trigger the development of depression in humans.

Prefrontal cortical enlargement in humans and associated cognitive complexities raise additional concerns for animal models of psychiatric disorders (Keverne 2004). The difficulty stems from problems in identifying homologous brain regions in humans and animals (Porrino and Lyons 2000;

Preuss 1995; Sasaki et al. 2004), especially for the rodents now widely used in neuroscience research. Transgenic mouse models likewise require homologous genes, and the resulting mouse phenotypes are not necessarily isomorphic with the human condition, because genes expressed on different backgrounds can produce different phenotypes (Yoshiki and Moriwaki 2006).

Despite these concerns, many important aspects of human psychiatric disorders are amenable to modeling in animal research. Because the life span of most animals is shorter than that of humans, longitudinal studies of development are facilitated by animal models. Randomized, controlled experiments can be conducted in animals without the common confounds that characterize clinical studies, such as comorbidity, polydrug abuse, and medication effects. Animal models also provide brain tissue of the highest possible quality for cellular and molecular research. Discoveries first made in clinical settings and subsequently tested in animals form the foundation of psychiatric neuroscience and will continue to play a key role in psychopharmacological research.

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