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Creation of new neurons critical to antidepressant action in mice

Blocking the formation of neurons in the hippocampus blocks the behavioral effects of antidepressants in mice, say researchers funded by the National Institutes of Health (NIH). Their finding lends new credence to the proposed role of such neurogenesis in lifting mood. It also helps to explain why antidepressants typically take a few weeks to work, note Rene Hen, Ph.D., Columbia University, and colleagues, who report on their study in the August 8th Science.

"If antidepressants work by stimulating the production of new neurons, there's a built-in delay," explained Hen, a grantee of NIH's National Institute of Mental Health (NIMH) and National Institute on Drug Abuse (NIDA). "Stem cells must divide, differentiate, migrate and establish connections with post-synaptic targets a process that takes a few weeks."

"This is an important new insight into how antidepressants work," added NIMH director Thomas Insel, M.D. "We have known that antidepressants influence the birth of neurons in the hippocampus. Now it appears that this effect may be important for the clinical response."

Chronic stress, anxiety and depression have been linked to atrophy or loss of hippocampal neurons. A few years ago, Hen's colleague and co-author Ronald Duman, Ph.D., Yale University, reported that some antidepressants promote hippocampal neurogenesis. But to what effect? To begin to demonstrate a causal relationship between these newly generated cells and relief from depression, researchers would have to find a way to prevent their formation in a behaving animal.

The researchers first showed that mice become less anxious they begin eating sooner in a novel environment after four weeks of antidepressant treatment, but not after just 5 days of such treatment. Paralleling the delay in onset of antidepressant efficacy in humans, the chronically-treated mice, but not the briefly-treated ones, showed a 60 percent boost in a telltale marker of neurogenesis in a key
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Contact: Jules Asher
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
7-Aug-2003


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