Week 2

I thought it was interesting that both Chaudhury and Tye addressed the relationship between dopamine and depression-related behaviors in the VTA using optigenetics, but found such conflicting results. The main experimental difference between the two papers was Chaudhury’s use of the social defeat paradigm that induces severe stress, while Tye used a mild chronic stress paradigm to induce depressive-like behavior. Chaudhury found that VTA dopamine neurons firing to the nucleus accumbens induces a depressive phenotype via social defeat stress; however, Tye found that increased firing of VTA dopamine neurons reverses chronic mild stress. This demonstrates that different stressors may cause opposite response from VTA pathways. It is interesting to extend these findings to the potential therapeutic value in application to humans; could varying degrees of stress activate opposing pathways in the VTA in humans? Furthermore, once our understanding of mental illness and depression has expanded, could antidepressants eventually be designed to treat a specific type of stress depending on its severity? Additionally, I thought it was noteworthy that both papers acknowledged that stress and depression can induce opposite pathways, despite both papers being published in the same year and volume.

While I generally found that the experiments were well designed in both papers, there were a couple experimental procedures that raised a few questions. As a few of my peers mentioned, the Chaudhury paper employed a social defeat paradigm for only ten days, while Tye et. al used a chronic stress paradigm to induce depressive-like symptoms for eight to ten weeks. Was this extreme difference in time length for administering stress paradigms due to the difference in severity between the two stress models? Furthermore, is ten days sufficient to induce a depressive state, even if using a severe form of stress? Regardless, Tye’s approach seems more valid as an inducer of a depressive-like state, as antidepressants take as long as six to eight weeks to begin to relieve symptoms. Additionally, Chaudhury only employed two measures to confirm mice were indeed experiencing a depressive-like state: the sucrose preference test and social interaction test. Tye employed more measures of depression: a forced swim test, tail-suspension test and sucrose preference, which I believe adds increased validity to their findings.