Animal Models of Depression Response

In these articles, Santarelli et. al (2003) and Bessa et. al (2009) begin by pointing out that neurogenesis is relevant in the hippocampal circuit and that it relates to neural plasticity. Additionally, both discuss how stress, as a trigger of depression, reduces both neurogenesis and plasticity. Santarelli et. al (2003) argue that blocking the neurogenesis induced by antidepressants essentially blocks the antidepressant effects, while Bessa et. al (2009), believe that it is the neuronal plasticity which aids the antidepressant drugs in being effective. In the Santarelli et. al (2003) paper, they used x-irradiation to disrupt hippocampal neurogenesis and block the effects of antidepressant treatment. Bessa et. al (2009), however, noted that antidepressants improved behavioral signs of depression independent of stimulating neurogenesis. Additionally, they observed altered synaptic function, which indicated that it was the neuronal plasticity that assisted antidepressant drugs in their actions. In their conclusion, Bessa et. al (2009) refute the findings of Santarelli et. al (2003) by stating that antidepressants promote neurogenesis, but are not critical.

After reading both papers, I think that both have different aspects of truth. I think that Bessa et. al (2009) are correct in their conclusion that antidepressants major role is to reestablish neural plasticity. I think that Santarelli et. al (2003) were correct in their determination that neurogenesis is an important aspect of the behavioral effects of antidepressants, but based on Bessa et. al (2009) I believe that it is not critical. In the results section of the Bessa paper, they stated that statistical analyses failed to show an interaction between the antidepressants and MAM (a drug which reduces neurogenesis). With the result that there was little to no reduction in antidepressant effects when MAM was administered, I think that Bessa et. al (2009) were likely correct – antidepressants largely work to reestablish neural plasticity, and neurogenesis is likely a side effect.