Week 1: Santarelli and Bessa

Santarelli et. al investigated the role of anti-depressant drugs in neurogenesis, and came to the conclusion that the behavioral effects observed by someone taking anti-depressants are mediated by neurogenesis in the hippocampus. While reading the paper, I found myself convinced with Santarelli’s method and findings. However, upon reading the Bessa et. al paper, I began to have some problems with Santarelli’s work.

First, I did not think the NSF test was a good enough way to assess the behavioral effects of the drugs, especially considering that Santarelli did not first mimic depression in the mice. On the other hand, Bessa used three tests to investigate antidepressant efficacy, as well as the chronic mild stress paradigm to mimic depression in the rats. (I am not convinced that CMS is the perfect depression model, but it seems like the best possible option that exists). Another difference between the two papers was Bessa’s use of MAM vs. Santarelli’s use of x-ray irradiation. Bessa tested their MAM-treated rats for locomotor activity and fur quality to ensure that the MAM was not affecting their general health, something that Santarelli did not do. On top of that, the x-ray also affected regions above and below the SGZ, which may have played a role in Santarelli’s results.

Despite all this, I think the Santarelli paper was a good starting point in investigating the relationship between antidepressants and neurogenesis, and it gave Bessa something to work off of. Ultimately, I believe that because antidepressants restored baseline levels in sucrose preference and the FST, regardless of whether or not neurogenesis was decreased due to MAM, Bessa proved that antidepressants would have behavioral effects even without stimulating hippocampal neurogenesis. That isn’t to say that Santarelli was entirely wrong. Bessa also noticed that when it comes to the NSF test, MAM does block the effects of the drugs. Neurogenesis does seem important in this case, and Bessa argues that this may indicate that new neurons generated because of antidepressants actually modulate anxiety. I would be interested in seeing whether or not this same effect would be observed in other anxiety-inducing tests, such as the elevated plus maze.