Animal Models of Depression - Week 1 Response

Both Santarelli et al. and Bessa et al. present strong cases for the underlying mechanism through which antidepressants function. Santarelli et al. argues that hippocampal neurogenesis is required for antidepressants to have a behavioral effect. I found that research to be rather compelling as they first demonstrated the necessity of the 5-HT_1A receptor for fluoxetine-induced neurogenesis, and then used irradiation experiments to further support their hypothesis. However, once I began reading the article of Bessa et al., which challenges Santarelli et al. quite straightforwardly, I understood that the issue is much more complex. Bessa et al. was able to indicate that the effects of antidepressants may actually rely on neuronal remodeling rather than neurogenesis.

Although Bessa et al. proposes a different hypothesis, countering that of Santarelli et al., there is still a clear lack of knowledge and further research that needs to be conducted in the field. This indicates to me that I cannot immediately accept nor dismiss either hypothesis, but rather perhaps there is a stronger connection there than what Bessa et al. was able to see.

In addition, I found it interesting that Santarelli et al. chose to use solely the novelty-suppressed feeding test for the majority of their experiments, whereas Bessa et al. utilized a variety of paradigms to test depression. Diseases such as depression, stress, and anxiety may manifest differently in humans and animal models, and considering how little we know about the mechanisms of these disorders, I would think that just one NSF test may not be enough to test for depression. When Bessa et al. incorporated the results from a wide variety of tests, I believe it made the evidence more compelling and perhaps more applicable to humans. Another related concern of mine was regarding the way depression was induced in the animal models. Because stress, anxiety, and depression are all so closely related, it seems difficult to differentiate, especially when it is being induced in animals. Although Bessa et al. presented strong findings that antidepressants reversed structural changes and other effects of the induced depression, I wonder how applicable it would be to humans who are not induced with depression in the same manner.