Pollak et. al and Li et. al

I found these papers to be interesting in that they were two very different mechanisms of study. Pollak et. al (2008) used behavioral therapy to attempt to reverse depression in several depression-like tests, and Li et. al (2011) found an almost immediate reversal of depressive symptoms using NMDA receptor antagonists like ketamine. While Pollak introduces an interesting concept with learned safety, I think that her model of learned behavior would not be practical in humans – the patient would have to know, prior to becoming depressed, that they would eventually need the safety signal. However, I was really interested in the Li paper, since many of my classes have discussed how antidepressants tend to have a waiting period before they seem to have an effect.

I really enjoyed the Li paper and found it very clear and concise to understand. Having taken psychopharmacology, I thought it was really interesting to read a paper that directly relates ketamine to depression. Li et. al. used behavioral models, microscopy and electrophysiology to strongly suggest that NMDA receptor antagonists would reverse depression within a chronic stress paradigm, which I thought was a very thorough analysis in addition to being very convincing. With respect to the flaws in previous papers, Li et. al. also administered drugs known to block the signaling required for ketamine, and found that when rapamycin blocked those signals, the sucrose preference, latency to feed and protein levels were all worse. I also found it interesting that they used DMSO in the same capacity as rapamycin, but not to the same effect. The effects of the DMSO resulted in no significant differences to control rats in animals exposed to both stress and ketamine, though when just exposed to the stress paradigm the DMSO animal values were similar to those of rapamycin.

Overall I thought that the paper clearly showed that NMDA receptor antagonists appear to reverse many of the effects of the chronic stress model of depression, but I would be concerned about the practicality of this model as well, since ketamine is considered a recreational drug. Despite this, I think that more research needs to be done about how ketamine could possibly become a fast acting treatment for depression, and perhaps look at using ketamine to provide short term relief at the same time as traditional antidepressants which can take several weeks to have an effect.