Hippocampal neurogenesis is required for antidepressant modulated anxiety improvement - Vasco Diogo

Santarelli et al.(2003) and Bessa et al. (2009) both look into the importance of hippocampal neurogenesis for the behavioral effects of antidepressants. At a first glance it might seem like the most recent article contradict the conclusions of the earlier one, in fact it replicate the earlier results. Both studies demonstrate that hippocampal neurogenesis is required for antidepressant facilitated improvement of anxiety like behavior in rats. This is evident in figure 5A of Santarelli et al.(2003) and figure 3 C of Bessa et al. (2009). Both figures show that without neurogenesis antidepressants do not improve latency to feed. There are, however, important differences to note in the methodologies and results of these 2 studies with regards to the anxiety paradigm. Santarelli et al.(2003) studies mice at basal level, while Bessa et al. (2009) utilizes a chronic mild stress paradigm to induce anxiety and depressive symptoms in the mice. In fact, the use of CMS results in increased baseline latency to feed prior to treatment compared to control mice. However, based on the results from Santarelli et al.(2003) it does not seem like this increase from baseline before treatment is necessary for the behavioral effect to occur. Another important difference between the studies is the method used for inhibiting neurogenesis in the hippocampus of the mice - Santarelli et al.(2003) used X-rays directed at the subgranular zone of the hippocampus while Bessa et al. (2009) used a cytostatic agent (MAM) due to worries regarding the inflammatory reaction caused by X-rays, despite the agent being less directed at the area of study. This complicates the interpretation of the results. While Bessa et al. (2009) defends that MAM reduces neurogenesis without negative effects on health, this is contradicted, as least partially, by the results in the novelty suppressed feeding paradigm. While X-rays do not increase latency to feed from baseline by itself, MAM does. This demonstrates that the effects of MAM are more widespread than those of the directed X-rays. Considering results from both studies, the effect of MAM on latency to feed is likely modulated by its effects on areas other than the subventricular zone and subgranular zone. In conclusion, both studies reach the same conclusion that hippocampal neurogenesis is required for the effects of antidepressants in anxiety symptoms. Furthermore, a better understanding of the effects of MAM on neurogenesis and its general effects on the brain could clarify what is causing the anxiety symptoms on the Bessa et al. (2009) study besides CMS, shinning light on the etiology of such symptoms.

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