Week II

            The Chaudberry et al. paper and the Tye et al. paper both set out to investigate the role dopamine (DA) neurons play in modulating depression. Tye et al. found that blocking DA receptors in the nucleus accumbens (NAc) decreased motivation while Chaudbury et al. found that innervating the mesolimbic dopamine pathway induced the susceptible phenotype, and inhibiting the pathway induced the resilient phenotype.

The mesolimbic pathway is known to regulate motivation; disruptions in the pathway will cause decreased motivation while stimulation of the pathway will increase motivation. It is counterintuitive that increased firing of NAc-projecting VTA dopaminergic neurons would cause the susceptible phenotype. Possible explanations of this phenomenon could be that in response to increased dopamine NAc cells may be less sensitive or dopamine stores are being depleted during this increased firing. In both of these scenarios NAc cells would be less active, which could explain the decreased motivation. However, even if that were the case it would not explain why Tye et al. found blocking dopamine receptors on NAc cells decreased motivation. Perhaps there is another variable that can account for these conflicting results.

            Chaudbury et al. also studied the effects of both stimulating and inhibiting the mesocortical pathway. The mesocortical pathway is implicated in motivation and emotional response. Chaudbury et al. found that stimulating VTA-mPFC neurons did not have an effect but inhibiting VTA-mPFC neurons induced the susceptible phenotype when measured by social interaction. Of note is the result that the susceptible phenotype was not induced when measured by sucrose preference. The sucrose preference test is used to measure anhedonia, a key symptom in depression. It is curious that the researchers chose to use the sucrose preference test as a measure of depressive behavior since the test does not test motivation. I believe forced swim test or tail suspension test may have been more informative assays because they are used to measure the animal’s motivation. Based on the methods used to measure the function of mPFC-projecting VTA DA neurons in Chaudbury et al. and the conflicting results regarding NAc-projecting DA neurons I am not convinced of the conclusions drawn in this paper regarding the roles of the mesolimbic and mesocortical dopaminergic pathways.