Should I, Or Shouldn't I?

By Michael Balter
ScienceNOW Daily News
27 July 2006

If you've ever worried about leaving the safety of one job for the excitement of another, or contemplated an extramarital affair, chances are you experienced conflict anxiety--the nervousness that occurs when we have to choose between competing impulses. Now, researchers working with mice believe they have identified the part of the brain responsible for this mental anguish. The discovery may aid the search for better drugs for anxiety and other emotional disorders.

The neural basis of anxiety first began to become clear in the 1980s, when researchers discovered that a drug used to treat anxiety stimulates receptors for a neurotransmitter called serotonin. More recent research has confirmed this connection (ScienceNOW, 27 March 2002), but scientists still know very little about the role that serotonin plays and where in the brain it acts.

To explore this role further, a team led by neurobiologist Jay Gingrich of Columbia University knocked out a gene in mice that encodes a serotonin receptor called 5HT2A, one of more than a dozen such receptors identified to date. 5HT2A is abundant in several areas of the brain and is thought to be involved in conflict anxiety. The researchers put the mice through a battery of tests designed to induce a conflict between safety and novelty-seeking behavior. In one experiment, the team recorded how much time the mice spent in dark versus brightly lit spaces. In another, the researchers placed the mice in an elevated maze, where some sections were completely open and others had walls. Compared to control mice, the knockout animals spent significantly more time engaged in novelty-seeking behavior. For example, they spent twice as much time in the brightly lit part of the cage, which mice usually avoid, Gingrich and his colleagues report in tomorrow's Science.

Next, the researchers gave the mice their serotonin receptors back, but only in the cerebral cortex. When the mice were put through the tests, they acted just as anxious as normal animals did. The finding bolsters recent brain imaging studies by other researchers suggesting that the cortex is the master regulator of anxiety.

The study is a "very interesting example" of serotonin's involvement in behavior, says Angela Roberts, a neuroscientist at Cambridge University in the United Kingdom. She adds that because serotonin receptors are frequent targets of therapeutic drugs, the findings "clearly have important implications for the treatment of a variety of neuropsychiatric disorders."