Animal Models of Depression/Antidepressant Response

These two articles represent scientific progression in their compounding inquiry of previously researched aspects in a field of study. In 2003, Santarelli et al. (2003) argue that hippocampal neurogenesis is paramount to the effect of antidepressant drugs on depression behavior as demonstrated by animal models. Years later, Bessa et al. (2009) investigate the pathophysiology of depression through a similar study yielding results that challenge the role of neurogenesis in the efficacy of antidepressants, and instead attribute their effect to neuronal plasticity in the hippocampus and prefrontal cortex. Importantly, Bessa et al. agree that antidepressants do indeed increase hippocampal neurogenesis as noted by Santarelli et al., but contend that neurogenesis is not essential to produce the effects of antidepressants that mitigate depressive behavior based on the results gained from using methylazoxymethanol (MAM) with antidepressants to stop neurogenesis while still producing the antidepressant behavioral effects. Interestingly, one of the concerns discussed by Santarelli et al. was that of uncertainty regarding if the hippocampal irradiation used could have affected the efficacy of the antidepressants by damaging or changing surrounding neuronal regions. By using MAM instead of irradiation, Bessa et al. eliminated many of the other consequences associated with irradiation, thereby specifically arresting neurogenesis as a more isolated target to show that while antidepressants do increase neurogenesis in the hippocampus, it is not a necessary process for drug effectiveness.

After reading these two articles, I was most interested in the duration of the efficacy of the antidepressants as well as of neurogenesis. In examining the mechanisms of antidepressants, neuroplasticity and neurogenesis are clearly important, but for how long do antidepressants affect them? It seems that many depressive patients relapse, or require a different drug to sustain the antidepressant effect, perhaps implying that neuronal pathways plastically alter to stop responding to the treatment. Also, I am curious as to how the rate of neuroplasticity and neurogenesis would be affected by antidepressants with a faster mechanism of action, such as Ketamine. I understand that further investigation should occur prior to investigating this line of inquiry, but I find them highly interesting nonetheless.