Mice without the gene for the serotonin receptor, so-called knockout mice, become very anxious, indicating the gene acts normally to prevent anxiety. Highly anxious adult mice move around less than normal in novel open or elevated spaces and are slower to eat food in such novel environments.
Through sophisticated and novel genetic tools, Dr. Hen and his colleagues were able to turn off and on the gene for the serotonin receptor in different locations in the mouse brain and during different times in development. They then could monitor the resulting anxiety-like behaviors in the animals.
First, they identified the locations in the brain that were important for the anxious behavior. When they shut off activity of the receptor in one part of the brain and there was no effect, they surmised the region probably did not have a role in anxiety. Conversely, if they shut down activity and the mouse became anxious, they surmised the region may be important for anxiety. Using this method, the investigators showed that certain types of anxiety may be located in the hippocampus and the cortex of the mouse brain. Then they determined what happened if they shut off activity of the serotonin receptor at different times in the mouses life. Mice without the receptor between five and 21 days after birth, become very anxious as adults, the researchers found. The serotonin receptor acting during that period therefore plays an important role in laying down the normal emotional circuitry of the mouse.
But removing the receptors activity in an adult mouse did not seem to have an effect on the animals behavior. The mouse acted normally despite predictions that it would become anxious since the prevailing paradigm suggests that lower levels of serotonin (or no receptor) in the adult brain lead to anxiety.