Animal Models of Depression/Antidepressants Response

Animal Models of Depression/Antidepressants Response

Both of these papers agree that there is a change happening with the neurons in rat animal models of depression as a result of introducing antidepressants. However, where the papers stray from one another are the mechanisms behind why antidepressants have been proven to effectively reduce behavioral symptoms of depression in animal models. Santarelli et. al (2003) believe that neurogenesis is the underlying cause of the effectiveness of antidepressants. However through a variety of different experiments, Bessa et. al (2009) shows that the effectiveness of antidepressants is due to the plasticity and changes in connectivity of the neurons. The prefrontal cortex and the hippocampus have been highly associated with depression, but as far as we know the prefrontal cortex does not have the ability to generate new neurons after birth (Bessa et. al, 2009). Bessa et. al (2009) blocked neurogenesis by treating animals with MAM (mitosis-suppressing agent), but the antidepressants were still effective for treating depressive behaviors in MAM-treated animals as well as vehicle-treated animals. This finding suggests that there must be another mechanism underlying the effectiveness of antidepressants in treating depressive behaviors. After reading both of these papers, I agree with Bessa et. al (2009) that antidepressants cause plasticity and connectivity changes in the neurons. However, I do think that this can be indirectly related to the neurogenerative changes that Santarelli et al. (2003) see in their experiments.  As we know, fluoxetine is a selective serotonin reuptake inhibitor (SSRI), which means that it is binding to presynaptic receptors on neurons to block serotonin from going back into the presynaptic neuron. Therefore, it is making the serotonin stay in the synapse and continue to bind to the postsynaptic neuron receptors causing the postsynaptic receptors to eventually up-regulate, which also may account for the latency in effectiveness of fluoxetine. The up-regulation of postsynaptic serotonin receptors would be a plastic change of the neurons, therefore furthering Bessa et. al (2009) research. However, the changes in the neurons and increase in activation of the neurons could lead to more neurogenesis as well. In my opinion, I think these two phenomena are probably closely related, however the connection may not be well understood.