OHSU Researcher Discovers Target for New Anxiety-Reducing Drugs
10/03/02 Portland, Ore.
Discovery may lead to nonaddictive drugs with fewer side effects
Researchers at Oregon Health & Science University (OHSU) have located a new target in the brain for the development of improved anti-anxiety medications. Through the use of a mouse model, researchers found that absence of a certain enzyme greatly reduces both anxiety and stress in the animals when compared to normal mice. The researchers believe this information can also be applied to humans and used in the development of better medications for serious anxiety disorders. The research is printed in the October issue of The Journal of Clinical Investigation. Jacob Raber, Ph.D., an assistant professor of behavioral neuroscience in the OHSU School of Medicine collaborated with researchers at the University of California, San Francisco, and the University of North Carolina on the project.
"To conduct this study, we used a strain of mouse that lacks an enzyme called protein kinase Ce (PKCe)," said Raber. "Earlier work showed that this enzyme interacts with GABA A receptors in the brain. As activation of GABA A receptors reduces anxiety, we tested whether PKCe deficiency reduces anxiety. This research demonstrated that a complete absence of the enzyme greatly reduces anxiety. While there are anxiety medications such as Valium currently on the market, these pharmaceuticals often act as a sedative. Even more concerning, many anxiety medications are addictive in nature. We believe this enzyme may be an ideal drug target for medications without serious side effects."
To examine stress and anxiety levels in the mice bred without PKCe, researchers recorded the animals' response to certain conditions and compared their reactions to normal mice. For instance, animals lacking PKCe were less timid about open lighted areas. These mice also exhibited reduced stress in response to being placed in a confined space for a limited amount of time.
"Much like mice, humans can also become stressed by their environment. Some people find riding in a crowded subway car to be a stressful activity," said Raber.
The research also helps explain the mechanisms involved in the body's creation of stress. With this information, physicians may use PKCe levels as a method of determining stress levels in their patients.
The State of California, the National Institute for Alcoholism and Alcohol Abuse, and other components of the National Institutes of Health supported this research.
Anxiety disorders include: obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, phobias and social anxiety disorder.
At any given time, an estimated 20 million Americans suffer from anxiety at levels that require treatment.
Anxiety disorders are the most common mental illness in the United States with 19.1 million (13.3 percent) of the adult U.S. population (aged 18-54) being affected.
People with an anxiety disorder are three to five times more likely to go to the doctor and six times more likely to be hospitalized for psychiatric disorders than nonsufferers.