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Week 1: Santarelli and Bessa

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These two papers, Santarelli et al. (2003) and Bessa et al. (2009) both investigate the method by which antidepressants cause their associated behavior effects – more specifically in regards to neurogenesis and neuroplasticity. 

Santarelli argues that neuroplasticity is necessary for antidepressants to induce desired behavioral effects. He tested this by measuring the feeding latency on the Novelty-Suppressed Feeding Test (NSFT) of rats by directing radiation to the hippocampal region to groups of rats both receiving and not receiving antidepressants. 

Bessa’s article is a response to Santarelli’s, as he also investigates the method behind antidepressants but argues that neurogenesis is not required to achieve the desired behavioral and molecular benefits of antidepressants. Bessa argues that neuronal remodeling and synaptic plasticity are the factors required for the behavioral efficacy of antidepressants, and explains that although hippocampal neurogenesis is promoted by antidepressants, it is not necessary for them to work. 

Although these papers have differing conclusions, I do not see them as contradictory. They both agree that neurogenesis is involved with antidepressant function, but Bessa argues that it is not the required event that makes antidepressants effective. Bessa’s experiment was more robust and rigorous because he 1) tested depressive behavior through several paradigms and 2) acknowledges the problems with X-ray methods and instead uses methylazoxymethanol (MAM) to block neurogenesis. 

Something that stood out to me when reading Santarelli’s paper was how he simplified depression. Santarelli only measured the behavioral efficacy of antidepressants in one way – through the Novelty-Suppressed Feeding Test (NSFT). Even in animal models, it is important to recognize the complexity of depression and the variety of symptoms and behaviors that antidepressants can affect. Bessa’s investigation was more thorough in its methods as it tested the behavioral efficacy of antidepressants through a variety of methods, specifically the Sucrose Preference Test (SPT), the Forced Swimming Test (FST), and the NSFT. Overall, Bessa’s article painted depression and the functionality of antidepressants in a more complicated and intricate way which I believe speaks to the multidimensional nature of the illness and its effects.

As far as future research goes, I would be interested in seeing the comparative hippocampal neurogenesis and neuronal remodeling of several more different kinds of antidepressants. I am not aware specifically of the molecular differences in varying types of antidepressants (as well as the differences in their behavioral effects) but would be interested in seeing if the neuronal remodeling changes across types.

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