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Post 2:Dopamine circuits and recovery from stress

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            The two papers this week were published in the same year, in the same journal, and on the same topic. They both looked at dopamine’s role in depressive-like behaviors. Both groups utilized optogenetics and phasic firing in the ventral tegmental area. With all of the similarities, it was shocking that both research groups came to completely different conclusions. After reading the papers, I went back to re-read them to establish the differences that could account for the opposite conclusion. The main methodology difference that I found was in the stress protocol. Chaudhury used a social-defeat stress model and Tye used a chronic mild stress paradigm. According to the articles, both are established models for inducing depressive-like behaviors. So, why did phasic firing in the first experiment lead to resilient mice becoming susceptible while in the latter experiment, it led to the rapid rescue of this depressive phenotype?
            My best guess would be that the social-defeat stress model established more of an acute depressive state, whereas the chronic mild stress parallels chronic depression. This thought was validated when I read the article in Discover. The author creates an analogy with getting mugged and being consistently worried about job security. The different experiences could alter the brain in a different way, even though they both may act within the same circuitry. Relating this back to our discussion last week, depression presents itself in many forms. We talked about how anxiety closely relates to depression and how anxious behavior is often indicative of depression. But depression does not always manifest itself in anxious behavior – some people can’t get out of bed, are lethargic, and have no interest in things. Perhaps the differing results then confirm what we already know: depression affects everyone differently. This then raises a lot of questions. If depression affects people so differently based on their experiences, what is the best way to go about studying it and ultimately treating it? If there was such a quick reversal of effects in these studies, is there a way for us to see a quick reversal of depression in humans without waiting for SSRIs to kick in?

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