Week 2: Tye et al. & Chaudhury et al.

            Both Tye et al. (2012) and Chaudhury et al. (2012) are papers that investigate phasic activation of the ventral tegmental area’s dopaminergic output as it relates to depression and depressive symptoms in mice that have been subject to stress. The most salient aspect of these papers was use of optogenetics in both, a very modern method that nullifies the blunt temporal and spatial resolution of traditional pharmacological modulation as well as providing an causal immediacy of behavioral or physiological effects.

            Tye et al. found that inhibition of the VTA’s dopamine output (namely to the nucleus accumbens) directly induces depressive symptomology in mice, while activation of the VTA could immediately reverse chronic mild stress-induced depressive behaviors. However, Chaudhury et al.’s paper argued, seemingly in complete contradiction to Tye et al.’s findings, that VTA tracts to the NAc produced depressive symptoms and high susceptibility in social stress specifically in stressed mice when stimulated, and increased resilience and non-depressive symptoms in previously socially-defeated mice.

While these two studies seem diametrically opposed despite their extremely similar methods, there is a notable difference (as has been pointed out in some of my colleague’s responses) in the stress paradigm each group used. Chaudhury et al. implemented a twice-a-day, 10-day social stress paradigm wherein the subject mouse was dominated by then placed into proximity of a larger mouse for two minutes and ten minutes at a time, respectively. Tye et al. meanwhile subjected their mice to a much more intense chronic mild stress paradigm of twice a day, multiple hour, randomized stressors such tilted cages, wet bedding, light/dark alterations, as well as food and water deprivation for eight to ten weeks. These sample groups are completely different and thus the two experiments should not be seen as parallel. Chaudhury et al’s social stress paradigm was apt for the social behavioral tests used, but may not be indicative of systemic, uncontrollable stress in the way that Tye et al.’s was and tested for with its variety of diagnostics. However, while both used sucrose prefence, perhaps a social aspect to Tye et al.’s tests would be useful, and possibly the data from Chaudhury et al.’s apparent use of open field and elevated plus tests as mentioned in their methods would be illuminating.