Week 3: Pollack and Li

Both of the papers this week examined different treatments for depression. Li et. al (2011) looks into the glutamate N-methyl-D-aspartate (NMDA) receptor agonist, ketamine, as a treatment for chronic mild stress. Li et. al (2001) used rapamycin to determine a specific pathway of action that ketamine works. Ketamine effects mTOR-dependent alterations in the spine/synapse (Li et. al, 2011). This pathway is responsible for synaptic plasticity by making proteins that are required for synaptogenesis (Li et. al, 2001). Ketamine is an amazing new anti-depressant treatment, because it is fast acting and can reverse behavioral effects of chronic mild stress. By studying rapamycin with ketamine, a better understanding of how ketamine works to reverse depressive symptoms was established. I liked how they tested the sucrose preference test over time to determine how ketamine works on a long term basis, and Li et. al (2001) demonstrated that ketamine continues to work even 3, 5, and 7 days after treatment. However, after 7 days of treatment the effects of behavior in the sucrose preference test declined, but the effect was still significant compared to the baseline (Li et. al, 2001). I would've liked for this paper to have demonstrated other behavioral tests to show the effects of ketamine, because the difference in hunger is a variable effect we see in human depression. I think it would have been interesting to look at the novelty suppressed feeding test over time after treatment to ketamine to see if the same results continued to be present over time. Li et. al (2001) additionally explored how ketamine and unpredictable chronic mild stress affect firing of excitatory post-synaptic current, and they found that ketamine reverses the firing effect after chronic mild stress. However, the exact mechanism that is happening with the firing post-synaptically is still not well understood. More studies need to be performed to better examine this interaction.

In the second paper, Pollack et. al (2008) looked at learned safety as a mechanism to prevent stress in mice. I liked this study, because they looked at a lot of different animal models as well as changes in the brain to try to determine how learned safety was affecting mice exposed to stress. This article shows that having safety signals can be equal to fluoxetine treatment (Pollack et. al, 2008). The mice that had been safety-conditioned showed an increase in BDNF (Pollack et. al, 2008). BDNF is a neutrophic factor that is expressed when it is helping synaptogenesis occur or helping existing neurons survive. This paper also looks at different genes and mechanisms to try and figure out how this learned safety is working in the brain. This experiment blocked the serotonin receptors and Pollack et. al (2001) did not find to affect learned safety, which is interesting because pharmacologically we typically use selective serotonin-reuptake inhibitors to treat depression in humans. So this may suggest that behavioral therapy and pharmacological treatments for depression act in different pathways.