Pollak et al. and Li et al.

The Pollak et al. 2008 and Li et al. 2011 articles provide enlightening insight into the vast methods of investigation of psychopathologies, specifically depression. While the former establishes learned safety as a viable behavioral model for depression with antidepressant effects, the latter demonstrates NMDA receptor antagonists as an effective pharmacological antidepressant.

With regards to Pollak et al., I too echo the sentiments of many that while this behavioral therapy model is incredibly interesting, I struggle to find how learned safety could effectively translate into a practical human treatment. Perhaps the use of a diverse range of situations and stimuli could make the therapy applicable to human adults, but the myriad external and interfering aspects that could influence such a behavioral treatment may diminish the efficacy.

That said, one facet of the Pollak studies I found particularly intriguing was the difference in results between learned safety and learned fear. In some cases, the results yielded were opposing. For example, learned safety training decreased the number of times mice entered into the closed arms of the elevated plus maze (an indication of decreased anxiety), while learned fear trained mice had an increased number of entries into the closed arms (an indication of increased anxiety). Contrastingly, learned safety mice had an increased number of times of entry into the open arms of the maze (less anxiety) while learned fear mice did not experience a significant change in number of entries into the open. This was also the result for immobility in the forced swim test as well. I found it interesting that sometimes the results were opposing between learned safety and learned fear, as I assumed would be the case, but other times the results were significant for one condition but not the other. These results serve as a testament to the diversity of mechanisms for safety and fear responses.

I greatly enjoyed both the presentation and content of the Li et al. article, and found their studies using ketamine to be both thorough and convincing. In comparing the two articles, I found their brief mentions of serotonin notable. Pollak et al. remarks that 5-HT1a receptors, as demonstrated by use of an antagonist, did not have a significant effect on learned safety. Li et al., however, suggests that ketamine reverses the deficit of 5-HT excitatory postsynaptic current in the PFC caused by chronic unpredictable stress, and is therefore implicated as an important part of the pathway. Thus, the two articles illustrate the complexity and ambiguity of the role of serotonin in psychopathologies such as depression.