Mesolimbic dopaminergic neurons and depression

        The two articles studying the role of mesolimbic dopaminergic neurons on depressive behavior published in the same issue of Nature are an important of why interpretations of results cannot easily be done beyond the scope of the models and methods being directly tested.

        Generally, results in the two papers show exactly directionality for the effects of mesolimbic DA neurons on depressive like symptoms. In short, Chaudhury et. al (2012) found that activation of VTA neurons induces depressive behavior and that inhibiting the VTA-NAc dopaminergic pathway induces resilience to depressive behavior. Tye et. al (2012) shows that inhibition of VTA neurons induces depressive symptoms and that inhibiting dopaminergic input into the NAc resulted in a more depressive behavior. These results indicate that there is a bidirectional effect of this pathway on depressive like behavior. Notably, the effects described by Tye et. al (2012) are observed in naïve mice, whereas the effects described by Chaudhury et. al (2012) are not. Specifically, the latter found no effect on sucrose preference upon activation of the VTA while the first found reduced sucrose preference after inhibition of the same area. This is a particular example demonstrating the overall observation that different models for measuring depression (chronic mild stress and chronic social defeat) result from different dynamics occurring in the same circuit. We can therefore only conclude that the effects of mesolimbic dopaminergic neurons on depressive behavior are bidirectional depending on the context.

        Had each of these two papers been published by itself, a reader could be tempted to make a more overarching conclusion regarding the role of this circuit on depression. Their concurrent publication is an important reminder that when searching for literature we should try to find opposing evidence to avoid being in an echo chamber and also to be conservative when taking more general conclusions from basic research, especially when it comes to making sense of results obtain from animal models in the context of humans.

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