9/19 Santarelli and Bessa

Santarelli et al. studied the role of anti-depressant induced neurogenesis in treating depression-like behaviors. However, the research from Bessa et al. suggests that anti-depressants treat depression through neuronal remodeling, rather than neurogenesis.

To determine the effects of antidepressants on depression-like behaviors in 5-HT_1a receptor knockout mice, Santarelli et al. used a novelty suppressed feeding test . Bessa et al. subjected Wistar rats to an unpredictable chronic mild stress (CMS) paradigm and used the sucrose preference, forced swim, and novelty suppressed feeding tests to assess depression-like behavior in Wistar rats. They found that the paradigm increased depression-like behaviors, but the symptoms were relieved after 1 week with imipramine and after 2 weeks with fluoxetine.  

Santarelli et al. used knockout mice to model depression. In the discussion, the authors acknowledge the problems with using knockout mice; the absence of the 5-HT_1A receptor during development causes anxious behavior. This could effect the results of their experiment, because the mice’s behaviors could be because of the developmental deficit instead of the depression model. Bessa et al. used the CMS to induce depression-like symptoms in rats. This method has a better translational value to humans than knockout mice. The authors stated that the loss in hippocampal and PFC volume is similar to the reduction in volume that depressed humans experience. In both rats and humans, the atrophy can be reversed by chronic antidepressant treatment. This supports the idea that antidepressants work through neuronal remodeling instead of neurogenesis. It is important for anti-depressant researchers to do studies that are translational to humans so we can create more effective treatments for patients with depression.

Santarelli et al. irradiated the SGZ of the mice to decrease neurogenesis while administering antidepressants.  However, Bessa et al. pointed out that irradiation requires a recovery period before the mice can be given antidepressants, which might affect the results of the experiment. Instead of irradiation, Bessa et al. used MAM, a drug that reduces neurogenesis without any noticeable health deficits.