Week 3 Articles

The use of Ketamine in the reversal of depressive symptoms came as a very concise and readable argument in the Li article, resulting in a causal relationship between the drugs morphological and physiological responses.  The chronic unpredictable stress paradigm’s use of an array of stressors makes the physiological and behavioral findings easier to appreciate and provides a more robust control for the experimental study.  After positively identifying Ketamine as a reversal agent in the SPT and NSFT, rapamycin was introduced to the study providing a negative control for the behavioral ramifications of ketamine.  This testing confirmed the requirements of the mTOR signaling pathway in the administration of Ketamine, a possible key to future isolation of ketamine’s antidepressant efficacy in reversing spine density and synaptic protein levels.

The extra data intelligently collected for SPT, at subsequent days after drug administration, highlights the fact that Ketamine not only has relatively immediate effect, but also extended activity. The rapid and long lasting (7 days) effects of Ketamine pumps the brakes on my developing understanding of depression.  From previous discussion I’d been thinking of synaptic plasticity as a necessarily gradual and delicate process, especially in the context of depression, demonstrated by the delayed effects of certain pharmaceuticals.  I’m inclined to believe this is only skimming the surface of the variability in neural plasticity that will lead to integral future discoveries.   

In contrast to the Li article, the Pollack paper examined a behavioral treatment of depression in a breadth of models and experimental levels.  Learned safety experimentally proved to induce anti-depression related biological changes and have behavioral outcomes similar to those of pharmaceuticals.  However, I struggle to see how behavioral therapies can be properly studied in animal models.  Behavior, hard enough to define in itself, is unique in its balance of biology and psychology.  Animal models provide solid insight into chemical activity and physiological changes in the brain as well as subsequent observation of quantifiable behaviors.  My discomfort comes from translating the weight a behavioral input would have in a rodent to that of what it would be to condition people in the context of their individual lives.