Week 1

While the two papers by Santarelli (2003) and Bessa (2009) both addressed the relationship between neurogenesis and the behavioral effects of antidepressants, Bessa et. al provided a more convincing presentation of their research. I first read the Santarelli paper; it was only after reading Bessa’s paper that the flaws in Santarelli’s paper became more apparent. First, the Santarelli paper merely adapted the novelty-suppressed feeding (NSF) paradigm as a measure of antidepressant effectiveness. However, as previously discussed, the NSF test is primarily used for assessing anxiety; while anxiety is often present in a depressive state, this paradigm is not ideal for examining neurogenesis levels in depressed mice. Furthermore, Santarelli did not discuss assessing the feeding drive of mice before administering antidepressants; this standard seems essential to establish prior to administering a NSF test to serve as a baseline for comparison. Despite these shortcomings, Santarelli still clearly demonstrated the effects of antidepressant administration on neurogenesis.

At a quick glance, it appears that Bessa refutes the data found in the Santarelli paper. However, Bessa seemed to adapt the Santarelli hypothesis and modify it to form a slightly different perspective: that while neurogenesis is indeed a component of antidepressant mechanism, neuronal plasticity and connectivity seem more specifically involved. Bessa observed these experimental design flaws from the Santarelli paper and improved them dramatically, first by employing several paradigms instead of just one to establish the effectiveness of the antidepressants. Bessa’s team also presented a vast amount of quantitative data involving volumetric changes and dendritic analysis that supported their findings. I also found Bessa’s use of MAM to reduce neurogenesis to be an effective negative control. Bessa found that MAM-treated and vehicle mice were relieved of CMS-induced depression after treatment with antidepressants to the same extent, further strengthening their claims that neurogenesis is not the critical event for the behavioral effects of antidepressants.

Both of these papers addressed the effects of 5HT-1A receptors in antidepressant-induced neurogenesis. However, further research could include investigating the effects of antidepressants targeting other serotonin subtypes on neurogenesis. Other antidepressants that target monoamine receptors for dopamine and norepinephrine could also be analyzed for their effects on neurogenesis.