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Week 2- Dopamine Modulation of Depressive-like Behaviors

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The Chaudhury et al paper explored the neural circuit mechanisms involved in the dopamine modulation of certain symptoms of depression. In this study, the researchers looked at social interaction and sucrose preference as part of their social-defeat paradigm, which has been shown in the past to be indicative of depressive-like behaviors. Although I initially did not completely see the connection between the social-defeat stress model of depression and the tonic vs phasic firing of dopamine neurons, it seemed that susceptibility and resilience to stress played a role in the functional/behavioral effects of dopamine firing. It was interesting to see how chronic mild stress with phasic firing of VTA dopamine neurons converted even resilient mice into susceptible mice. 
The Tye et al paper similarly looked at the dopamine modulation of depressive-like behaviors, focusing on motivation with the forced swim tests and open field tests, followed by measurement of anhedonia by quantifying the sucrose preference test. Immediately after reading this, it seemed to me that this article did a better job of explaining to the audience their reasoning behind their choice of protocols and how it related to modulation of VTA dopaminergic neurons. The most important distinction between the findings in these two articles is that this study came to the conclusion that inhibition of the VTA dopamine induces depressive-like behaviors and chronic mild stress causes this depression-like behaviors to continue for extended periods of time. Further, it seemed to directly link the nucleus accumbens role in this pathway but did not expand on the circuitry in the way that Chaudury et al did in their study.

One question that these types of studies tend to raise is the question of whether the results of these experiments are clinically applicable. Since modeling depression in mice in a way that reflects clinical depression is very difficult, one valuable piece included in the first article (Chaudury et al) was the fact that they used two separate kinds of mice- the ChR2 mice who were susceptible to developing depressive behaviors after exposure to chronic mild stress and the eYFP mice who acted as the resilient controls. This is important because even in humans, people react differently to the stressors in their life. Further, severe stressful situations such as trauma can trigger a depressive episode, which would be consistent with the result that the mice expressed anhedonia-like behaviors with increased phasic firing of dopaminergic neurons in the mesolimbic pathway.

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