Project Summary

Rene Hen, Ph.D. (Distinguished Investigator 2003) of Columbia University, seeks to understand the mode of action of medications that are currently used to treat a variety of depression and anxiety-related disorders.  Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant, but their mechanisms of action are largely unknown, and particularly, the reason for their delayed onset of action (4 - 6 weeks) is not understood.  Dr. Hen seeks to demonstrate that the increased hippocampal neurogenesis elicited by chronic antidepressants contributes to the behavioral effects of these drugs, by constructing “rescue” mice that express serotonin (5-HT1A) receptors only in the hippocampus.  He will also test whether an X-ray-induced blockade of hippocampal neurogenesis will disrupt the behavioral effects of antidepressants in various rodent models.   He hopes to prove that stimulating hippocampal neurogenesis is a requirement in order for antidepressant medications to exert their effect.  If true, it would seem that hippocampal plasticity is not only critical for learning and memory, but also for emotional responses.  Specifically, growth factors or environmental manipulations which have been shown to stimulate hippocampal neurogenesis may become components of future therapies. 

Program Area: MULTIPLE FOCUS AREAS\Anxiety Disorders/Unipolar Depression

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