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Timing of chemical signal critical for normal emotional development

A signaling protein suspected of malfunctioning in anxiety and mood disorders plays a key role in the development of emotional behavior, report researchers funded by the National Institute of Mental Health. Mice lacking it in frontal brain circuits during an early critical period fail to develop normal reactions in anxiety-producing situations.

Rene Hen, Ph.D., Columbia University, and colleagues created mice that lacked the protein, which brain cells use to receive signals from the chemical messenger serotonin, by knocking-out the gene that codes for it. As adults, these "knockout" mice were slow to venture into -- or eat in -- unfamiliar environments. By selectively restoring, or "rescuing" certain populations of the receptor proteins, the researchers have now pinpointed when and where they enable the brain to cope with anxiety. Hen, Cornelius Gross, Ph.D., Xiaoxi Zhuang, Ph.D, and colleagues report on their discovery in the March 28, 2002 Nature.

Brain neurons communicate with each other by secreting messenger chemicals, such as serotonin, which cross the synaptic gulf between cells and bind to receptors on neighboring cell membranes. Medications that enhance such binding of serotonin to its receptor (serotonin selective reuptake inhibitors, or SSRIs) are widely prescribed to treat anxiety and depression, suggesting that the receptor plays an important role in regulating these emotions.

Behavior of the animals in the study mimicked human anxiety. The mice bred not to express the gene that codes for the serotonin receptor (5-HT1A) moved around less than normal animals in open spaces, balked at entering elevated mazes, and were slower to begin eating in such novel environments. Yet, the researchers didn't know which of two populations of serotonin receptors -- one in the forebrain and another deep in the brainstem -- was responsible. To find out, they crossed the receptor knockout mice with mice engineered to turn receptor expres
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Contact: Jules Asher
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
27-Mar-2002


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