Week 1: Santarelli et al., Bessa et al.

The experimental design of Bessa et al. (2009), when considered as a response to Santarelli et al. (2003), is notable in a few significant ways. Firstly, parallels in paradigm, analysis, and anti-depressive drugs administered was necessary to produce similar conditions to the original experiments so as to at once affirm the partial validity of the original findings before demonstrating the parallel, likely more salient neural processes at work. Secondly, the omission of questionable methods from Santarelli et al. such as irradiation in favor of the neurogenesis inhibitor methylazoxymethanol eliminates the broad scope of possible effects of radiation in favor of specific targeting of neurogenesis. Finally, the inclusion of more multi-modal analyses of the effects of anti-depressive drugs including directly quantifying plasticity-related mRNA expression as well as dendrite volume and proliferation offered a drastically more significant collection of data than was presented by Santarelli et al.’s single-factor analysis of BrdU and minimal behavioral testing.

In all, Bessa et al. was a prime example of well-thought out, broadly analytical science: taking an established theory (neurogenesis’ role in the effectiveness of antidepressant drugs) and at once confirming it as a partial factor while presenting parallel systems that work independent of the original theory, thus presenting a more holistic, multi-faceted analysis of the phenomenon at hand. However, this is not to say that the experiment was without flaws. While the rats did present depressive symptomology as indicated by performances in the forced swim, sucrose preference, and novelty suppressed feeding paradigms, it is uncertain how applicable those results can be to chronic depression or anxiety as the paper suggests rather than an induced disease such as post-traumatic stress disorder due to the inherently traumatic nature of the chronic mild stress protocol and the vast array of diseases that present the anhedonic symptoms upon which the experiments were based. Going forward, it would be beneficial to explore the hypothesis presented in the Bessa et al. discussion that new neurons formed under anti-depressive treatment integrate into emotional behavior networks. Comparing the morphology, destinations, and latency of plasticity of neurons formed under duress and under pharmacological alteration could give more insight into the basis of stress-based disease and treatment.