Chaudhury et al
Chaudhury
et al raises some interesting points about the tonic and phasic models
regarding social-defeat stress in dopamine neuron firing. According to their
research, the phasic model (20-Hz) induces more stress susceptibility and
social avoidance in addition to reduced sucrose preference as compared to
tonic-stimulated mice (0.5-Hz), however, their promoter, as I understand,
tyrosine hydroxylase is not necessarily a dopamine specific promoter. In fact,
they mention that they did discover non-dopaminergic cells in their study,
which is a demonstration of the non-specific binding that tyrosine hydroxylase
exhibits. Their study claims a direct link between the VTA and the
dopamine-neuronal firing patterns, but due to this non-specific binding I might
question its validity.
Additionally,
if resilience to social defeat stress is seen in the tonic model versus the
phasic model and their findings are correct, as I am suspect of, they claim
that there is a clear and consistent link with the NAc and the VTA. Severity of
stress seems to be paramount in this study and they demonstrate this by
switching from phasic to tonic models using optogenetics. I am unclear as to
how this expresses chronic and/or acute stress. Furthermore, how does this
model mimic antidepressant effects of ketamine, sleep deprivation, and deep
brain stimulation.
It is
understood that the NAc-VTA interaction is opposite that of the VTA-mPFC
pathway. This is demonstrated though anhedonic and reward pathways that are
demonstrated by the NAc-VTA and the VTA-mPFC. While it is possible that the
mPFC presents a significant reward pathway, I would rather hypothesize that this
effect could be seen because the mPFC suppresses information that in
inconsistent with conditioned reality. Therefore, the mPFC would suppress stress-related
information that no longer made sense to the brain and should antidepressants
be administered, perhaps it would work in aiding to suppress behavioral abnormalities.
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