Animal Models of Depression Response

          Both Santarelli et al. (2003) and Bessa et al. (2009) agree that neurogenesis is reduced in animal models of depression, and that treatment with antidepressants stimulates neurogenesis. What the two papers disagree on is the mechanism behind this. Santarelli et al. argues that neurogenesis is required for the behavioral effects of antidepressants to occur, while Bessa et al. states that neurogenesis is not at all necessary, and rather that antidepressants work through increasing neuronal remodeling and synaptic plasticity. I was very fascinated by the two papers’ opposing views about the significance of neurogenesis. Santarelli et al. used hippocampal irradiation to block neurogenesis, and found that the effects of antidepressant treatment are not seen in mice that were also exposed to irradiation. These results support the authors’ hypothesis that neurogenesis is necessary for antidepressants to have their effects, but it is important to recognize that there may be confounding variables and other explanations for the results. Perhaps the hippocampal irradiation had other consequences that may have lessened the effect of the antidepressants. If there were deleterious effects of the irradiation that the scientists were not aware of, then maybe it was these effects, rather than a lack of neurogenesis, that caused the antidepressants to lose their effect. This idea is supported Bessa et al. (2009) who demonstrated that neurogenesis is not, in fact, necessary for antidepressants to have their effect. Rather than using hippocampal irradiation to test the efficacy of antidepressant medications in the absence of neurogenesis, Bessa et al. utilized MAM. Administration of MAM in addition to the antidepressant medications did not affect performance on any behavioral test compared to mice treated with antidepressants alone. The results of this study demonstrate that, though antidepressants do stimulate neurogenesis, this is not necessary for the medications to have an effect, contrary to what Santarelli et al. proposed. I believe that it is likely that the hippocampal irradiation negated the positive effects of the antidepressants due to other reasons besides blocking neurogenesis. As a next step, I think it is important to conduct further studies in order to gain more evidence that, though neurogenesis is an effect of antidepressant treatment, it is not an essential component. Furthermore, I believe that more tests should be done to learn about additional effects of both hippocampal irradiation and MAM so we can assure that all compounding variables and effects have been controlled for. Future research will hopefully help us to more fully understand the mechanisms behind antidepressant medications.