Genetically Engineered Mice Exhibit Anxiety, Offering Insight Into Role Of Serotonin In Brain

Researchers led by a UC San Francisco investigator have genetically altered the serotonin brain system of mice, producing animals that exhibit anxiety, thereby offering an important new model for exploring the way in which the serotonin brain system contributes to anxiety in humans.

The model, reported in the December 7 issue of Proceedings of the National Academy of Science, could help researchers come up with more refined targets for psychiatric drugs. It also could serve as a model for examining inherited personality disorders involving anxiety, the researchers said. Overall, the model provides an important inroad for exploring the highly elaborate, inscrutable serotonin system, which regulates most, if not all, complex behaviors.

Serotonin is one of the brain's key neurotransmitters, which are signaling molecules that transmit chemical messages between brain cells, or neurons. The molecule communicates its messages through interactions with at least 14 distinct types of serotonin receptors, located on the surface of various types of nerve cells in the brain.

In most people, the neural system manages to maintain a normal balance of serotonin activity. In some, however, activity is either abnormally heightened or depressed in any number of different neural pathways. The type of impact serotonin has on the nervous system is determined by its success, or lack thereof, in reaching its target receptors, and the response that these receptors have to the neurotransmitter--either stimulating or inhibiting its activity.

While unusually elevated or inhibited serotonin activity has been implicated in many psychiatric disorders, scientists are unclear about the relative contribution of the various receptor subtypes to the regulation of particular behaviors. "It may be that the set of serotonin receptors regulating one type of behavior, such as feeding, differs from those controlling other responses, such as anxiety, depression and aggression," said the

Contact: Jennifer O'Brien
University of California - San Francisco

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