Pollak et al/Li et al

To begin, I would say that overall both of these papers have put forth two methods that could be extremely useful in future animal studies of depression treatments. However, I think it is clear that both techniques are a long way from being viable human treatments. Tamara and Jessica mentioned the issues with ketamine (and I’m sure more would arise), and I personally don’t see a way in which learned safety could be expressed in humans. While I think Pollak et al shed light on a very interesting and significant effect of learned safety, and provided lots of insight into potential mechanisms that underlie depressive behavior to direct further exploration, I think that this research may have less straightforward applications to human depression. The research into NMDA receptor antagonists done by Li et al, however, seemed extremely promising. I think they did a really good job showing how strong and fast the positive response to these drugs was, and made a strong connection to the mTOR pathway as a mechanism of action. In particular, the use of rapamycin as a control to inhibit the mTOR pathway really convinced me that they had identified at least one necessary component, although more may exist.

There were, however, a few points where I would have found more information useful. While they did track the effects of ketamine for 7 days, I wondered why they didn’t go on until the effect wore off. The restored sucrose preference began to taper off in Ro 25-6981 subjects by day 7, and it would have been interesting to see how long the ketamine effects would last. This would have given some more insight into how effective the drug might be, but I also think that a drug with such a strong effect for an extended amount of time is very powerful, and therefore very long lasting results might be a red flag, or at the very least something to take note of. Additionally, towards the end of the paper, Li et al stated that forced swim and tail suspension tests have “limited validity as measures of depressive behavior”, without any elaboration. This surprised me, given that I have read so many studies (including Pollak et al) that rely heavily on these tests to back up their research. I think it’s interesting how in just the few papers we have read in class there has been so much back and forth between which tests model depression well, and yet none of them have fully convinced me one way or the other.