Animal Models of Depression

In the two research papers by Santarelli et al (2003) and Bessa et al (2009), the mechanisms behind the action of antidepressants were observed using a variety of experiments. Both of the papers focus on the effects of antidepressants on the behavior of animal models, however there is a significant difference of opinion regarding how the antidepressants themselves actually function.

Santarelli et al (2003) suggest that neurogenesis is the necessary component of antidepressant efficacy. The generation of new neurons in the dentate gyrus of the hippocampus was recorded and tracked using BrdU. Upon administering different antidepressants to mice showing depressive symptoms, there was a significant increase in neurogenesis as seen with the BrdU tracker. Using x-irradiation of the hippocampus to stop neurogenesis, Santarelli et al (2003) found that the antidepressants had little to no effect on the animal subjects displaying depressive symptoms. However, irradiation of the brain regions could have had other unknown effects on the mechanisms of antidepressants, which could have caused the lack of response to the medications. In contrast to Santarelli et al (2003), Bessa et al (2009) suggested that neurogenesis is important in order to alleviate depressive symptoms, however, the experiments they conducted showed that neurogenesis is not necessary in order for antidepressants to be effective. Bessa et al (2009) instead suggested that neuronal plasticity and dendritic remodeling are keys to antidepressant activity. MAM was used to stop neurogenesis in order to see if it was required for effective treatment of depression. It was found that the behavioral symptoms of depression were still alleviated without neurogenesis occurring. In addition, in the Bessa et al (2009) paper, chronic mild stress exposure reduced the volume of the hippocampus and the prefrontal cortex. After antidepressant treatment, the volumes of these brain regions were restored to normal, and there was significantly more dendritic arborization in these regions. This suggests that the reorganizing of neural circuits may be the main reason for increased plasticity and decreased symptoms in antidepressant treated subjects, with neurogenesis helping to contribute to these effects.

I believe that Santarelli et al (2003) were on the right track with their investigation of neurogenesis as the main mechanism behind antidepressant action in animal models. However, it is evident based on Bessa et al’s (2009) experiments that there are more significant processes involved in the response to antidepressants, such as neuronal remodeling and plasticity.