Chaudhury vs Tye: Complexities in Stress-Induced Depression Models

As I was reading this week's papers, I found it most interesting that they seemed to reference each other fairly often in terms of their respective choices of stress paradigms. Both papers address the limitations of their respective stress-induced depression models. It is unclear which set of models is  more viable since VTA dopamine neurons seem to react differently to stress depending on its severity. In this way, the changes in these neurons are "context dependent". This brings about the question of how one might measure the severity of a particular stress paradigm. How do scientists decide whether a source of stress is "mild" or "severe"? One thing I would have liked to have seen done by these researchers is measure levels of cortisol in animals that underwent chronic mild stress as well as the social defeat paradigm. Do both paradigms increase cortisol to the same extent? If they do increase cortisol, how long does the increased cortisol level persist after the stress is removed? Perhaps this can give more insight as to how the different stress paradigms are affecting the animals on another physiological scale. I also found it interesting that both papers agreed that the ability to make rapid changes in this neural circuitry was important in a clinical aspect. Since most anti-depressant medications take 2-3 weeks to take effect, a faster-acting drug would be highly advantageous in treating high risk patients. Both papers briefly mention that ketamine might offer a solution in this way.

I found the approach of the Tye et al paper to be particularly confusing. They exposed their experimental animals to a chronic mild stress paradigm and then tested their motivation using the tail suspension test (TST) and forced swim test (FST). Both the TST and FST seem to be situations that would induce some level of stress in the animals. However, the researchers did not test if the stress from these tests themselves would change VTA dopamine neuron function. This leads me to return to my previous idea about cortisol levels. If cortisol levels were measured after the TST/ FST in naive mice, it may be possible to determine how stressful they are in relation to the chronic mild stress paradigm to eliminate any confounding variables.