Li and Pollack

            Li et all, in my opinion, produced the most definitive argument on a topic that we have seen so far this semester. They covered all of their bases by showing both the behavioral and morphological effects of ketamine, as well as indicating the major potential pathway. Unlike many common antidepressants that take chronic use to produce effects, ketamine was shown to produce significant improvements in the sucrose preference test and novelty suppressed feeding test immediately after injection. The acute behavioral remedy was even shown to last seven days, which could be very useful clinically. The morphological deficits produced by the 21-day chronic unpredictable stress were all reversed by ketamine injection. The synaptic protein deficiencies, spine density reduction, and amplitude and frequency reductions of synaptic firing were all alleviated by a single ketamine injection. After literally listing four different things that ketamine fixes, Li et all went on to show a potential pathway for NMDA-antagonist using rapamycin. Rapamycin is known to inhibit the mTOR pathway, and when injected before ketamine it completely blocked the effects of ketamine. This is the one area of the paper that I think could use some buffing in future works. Just because we know what pathway rapamycin usually affects and that it blocks the effects of ketamine in this experiment, I don’t think we can definitely say that ketamine works through the mTOR pathway. I think further testing is needed for proof of this pathway.

            Pollack et all was a lot less convincing than Li et all. There were two major things from the Pollack paper that I particularly liked. I liked the step away from the usual pharmacological antidepressants that we are used to seeing tested. It was nice to see a potential clinical remedy of depression that does not need pills. It was also interesting how it was shown that the pathway of this learned safety is different from the pathway of typical antidepressants. The greatest strength of this paper was how they dove into the potential circuitry and connection behind the learned safety. Pollack proposed that the learned safety may affect the dopaminergic neurons of the VTA, which in turn may affect the D2R in the basolateral amygdala, Substance P mRNA, and then BDNF. It is this kind of circuit analysis that is needed to take the next step at understanding depression.