The serotonin transporter is the principal target of most commonly prescribed antidepressants. While chronic treatment with serotonin reuptake inhibitors (SSRIs) is effective in treating depression and anxiety, transient SRI treatment during the postnatal period has been shown to produce opposing alterations in the emotional behavior of adult mice and rats. It has therefore been hypothesized that alterations of serotonin signaling during a developmental critical period leads to permanent changes in the function of brain regions underlying emotional behavior. This proposal is part of a larger effort to characterize the neural basis of altered emotional function in this model. This particular project seeks to test the hypothesis that the adult phenotype is associated with changes in the anatomy and function of serotonergic neurons. In the first aim, immunohistochemistry will be used to quantify the projections of serotonergic neurons to regions ofthe brain which are involved in emotion, including the medial prefrontal cortex, hippocampus, amygdala, and nucleus accumbens. In the second aim, we will take advantage of recently-developed techniques for cell type-specific mRNA isolation to profile gene expression selectively in serotonergic cells, in order to understand the altered function of these neurons in the postnatal SSRI model. Postnatal antidepressant treatment causes permanent changes in emotional behavior in mice, and has Deen proposed as an animal model of depression and anxiety. A better understanding of how this treatment programs adult emotional behavior would provide a foundation for future research on how both early-life experiences and genes can predispose to depression and anxiety disorders. In addition, the postnatal period of SSRI treatment roughly corresponds to the third trimester and early months of human development;this research will contribute to our understanding of the potential risks of antidepressant use in pregnant women.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30MH084531-02
Application #
7993107
Study Section
Special Emphasis Panel (ZRG1-F03A-F (20))
Program Officer
Vogel, Michael W
Project Start
2009-12-01
Project End
2012-11-30
Budget Start
2010-12-01
Budget End
2011-11-30
Support Year
2
Fiscal Year
2011
Total Cost
$46,800
Indirect Cost
Name
Columbia University (N.Y.)
Department
Psychiatry
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032