Animal Models of Depression Response

            In both of these papers, researchers attempt to fathom the pathophysiology of depression. Santarelli et al. attributes neurogenesis as the key mechanism to the behavioral effects of antidepressants such as Fluoxetine using knock out mice and irridation to correlate the two phenomenon. Six years later, Bessa argues that while antidepressants can be attributed to increasing neurogenesis, it is structural changes in the hippocampus, such as synaptic plasticity and neuronal connectivity, which accounts for antidepressant drug action. Bessa does this by this time using MAM to block neurogenesis, and structural analysis and qPRC to measure synaptic plasticity and spine changes. Both research projects use BrdU as a marker + NeuN or GFAP to measure the presence of neurogenesis.

            While I see the reasoning behind both of these methods, I think that to properly disprove Santarelli, Bessa should have set up the procedure and used the same behavioral assays to match Santarelli’s, while changing one variable (the presence or absence of neurogenesis). Santarelli measured the behaviors of depression, focusing on the Novelty Supressed Feeding Test that measures anxiety, and then later uses the Chronic Unpredictable Stress paradigm when applying irridation. Bessa measures anxiety and stress, but also applies the sucrose preference test and forced swimming test to measure anhedonia and learned helplessness. Although I am not nearly as practiced as these researchers with the subject of depression, I believe that anxiety and stress may run slightly different pathways than anhedonia and learned helplessness, as the phenotypic behaviors in a person appear very different. If this is indeed true, it would be hard to disprove that neurogenesis is involved with stress using the sucrose preference test. At the end of Bessa’s article, it is noted that neurogenesis is needed for antidepressant relief of anxiety, which supports Santarelli’s research.

            I agree with Bessa’s logic that neurogenesis and antidepressant action may be an “epiphenomenon”, but I would like to see further research on the synaptic plasticity and neuronal connectivity theory, perhaps removing it as they did neurogenesis with MAM, to prove that antidepressant behavioral outcomes are dependent on this synaptic remodeling.