Both papers looked at the role of dopaminergic projection
from the VTA into the NAc in the modulation of depression, and yet they
presented contrasting results. However, I thought it was interesting how the
authors of both papers integrated the opposing results in their discussion and
considered the differences in models along with the limitations of their own
methods that could be contributing to such bidirectional outcomes.
On one hand, Chaudhury et al made use of a 10-day repeated
social defeat stress to induce the depression-like symptoms and relied on
social interaction and sucrose preference to quantify such symptoms. While their
methodology and protocol all made sense, I thought that the idea of assessing
depressive symptoms by only measuring these two parameters was very limiting in
terms of projecting the results into clinical applications. On the other hand,
Tye et al made used of a time-intensive chronic mild stress (CMS) paradigm and
relied on the TST and FST to measure the depression-like phenotype. The one point that I like more about the
methodology of Tye et al is that they had the open-field-test as an additional
measure to rule out any additional locomotor effects that could be contributing
to results from the TST and FST.
Going back to the idea of variability in context and severity
of stressors in addition to the behavioral assessments, researchers could fix
one of the two variables and investigate the differences in changing the
second. They could use the same models again but unify the behavioral tests,
and then induce stress using different paradigms. That being said, I think that
in all cases, there should be some additional measurement of stress based on
the stressors used given that the intensity might have a critical role in the firing
of VTA dopamine neurons. Maybe additional stress-related brain regions could also be monitored at the same time?
Overall,
I thought it was interesting to see how Tye el all summarized all the critical
points that could be good explanations for the differences in results seen in
the two papers. The types and severity of stressors should be further
investigated and controlled, and the behavioral tests should be as diverse as
possible for a better interpretation of results.
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