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Week 1: Santarelli and Bessa

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The articles written by Santarelli and Bessa, both aim to explore the neuro-modulating effects which influence the behavioral changes associated with anti-depressant (AD) medication. In 2003, Santarelli hypothesized that neurogenesis in the hippocampus was the primary mechanism of action of ADs which leads to an improvement in depressive-like behavior in rodents. They confirmed this hypothesis by measuring feeding latency in a novelty-suppressed feeding (NSF) test, often used to assess depression in rodent models. After treatment with several AD medications, and evaluation of behavioral tests, it was concluded that neurogenesis in the hippocampus played a major role in the behavioral modification of depressed rodents by measuring neurogenic factors in the subjects associated with neurogenesis.

The Bessa study was conducted 6 years after the publication of Santarelli's article concluding the effect of neurogenesis on behavioral modifications of ADs. The Bessa paper includes a far more comprehensive array of both behavioral and structural analyses post treatment with ADs. Their study also included the use of a cytostatic agent, methylazoxymethanol (MAM). This drug inhibited neurogenesis and was co-administered with the ADs in the different subgroups of animals. With the inhibition of neurogenesis, it was found that the behavioral modifications of ADs persisted in the chronic mild stress (CMS) animals. Meaning, the reversal of depressive-like behaviors was not dependent on hippocampal neurogenesis. They further explain the causality of the improvements of depressive-like behavior and accredit the improvements to neuronal plastic changes, rather than the birth of new neurons.

When analyzing the differences between the Santarelli and Bessa article, I found it most interesting that Bessa does not refute the finding of Santarelli, but builds off of them. Bessa does not deny the occurrence of neurogenesis as a result of the introduction of ADs, however, they do prove with the use of the cytostatic agent MAM that this is not the primary modulator of the behavioral effects of AD medication. In their discussion they introduce the idea of neurogenesis being important for the reduction of anxiety-like symptoms in rodents. As discussed by Bessa, while neurogenesis is not required for behavioral modification of depression with ADs, it does appear to play a vital role in their anxiolytic effects. This would be an interesting place for further research and development for a new hypothesis of the role of neurogenesis in the behavioral effects of modulating serotonergic pathways.

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