098-AP-99
EMBARGOED UNTIL 2 P.M. PDT MONDAY, AUG. 30, 1999
PROTEIN IN BRAIN MAY HELP REGULATE BODY'S REACTIONS TO STRESS
Discovery Could Lead to New Therapies for Anxiety and Other Mental Disorders
Irvine, Calif. -- Our ability to cope with stressful situations may be due partly to a tiny protein in the brain, a UC Irvine scientist and his colleagues have found. The finding in mice is the first to demonstrate how this protein works with other chemicals in the brain to control reactions to stress and eventually could result in new therapies and drugs to cope better with stress-related mental disorders.
Pharmacology researcher Rainer Reinscheid, Professor Olivier Civelli and researcher Hans-Peter Nothacker of UCI's College of Medicine and a team from Switzerland and Germany found that mice that were unable to produce the protein called orphanin FQ/nociceptin were unusually anxious in stressful situations, and were unable to adapt to stresses as well as mice that could produce the protein. The findings appear in the Aug. 31 edition of the Proceedings of the National Academy of Sciences.
Orphanin FQ/nociceptin is a small protein that Reinscheid and Civelli discovered about four years ago. It is found in a part of the brain called the amygdala and in regions of the hypothalamus, areas known to regulate reactions to stressful events such as pain and fear. Since their initial discovery, Reinscheid and his colleagues have been exploring the roles orphanin FQ/nociceptin may play in handling stress.
The researchers' latest study shows that mice lacking the genes that produce this protein reacted more nervously to new situations than mice that could produce it. In addition, they found that mice without the gene never seemed to adapt to repeated stresses; they instead continued to react with the same intensity. Usually, the body adapts to repeated stresses with increasingly calm responses: pulse rates slow, the body produces less adrenaline and other stress hormones, and behavior is less abrupt.
"By knocking out the gene that makes orphanin FQ/nociceptin, we can see for the first time what types of behavior this protein controls in the brain," Reinscheid said. "This experiment not only confirmed that orphanin FQ/nociceptin is essential for the body to manage stress, but that it is also needed for long-term adaptation to repeated stressful situations."
The research suggests that orphanin FQ/nociceptin normally acts against the body's tendency to create a "fight-or-flight" reaction to stress. This reaction includes the production of hormones by the adrenal and pituitary glands and increased activity in parts of the brain that control awareness and motor reactions. The reactions provide animals with an extra metabolic "boost," so they can either escape from or fight off threats.
Reinscheid believes that orphanin FQ/nociceptin's opposition to this "fight or flight" system results in carefully modulated responses to stress. If stress continues for too long or is severe, however, the body can develop adverse reactions. Mental illnesses such as anxiety disorders, depression or obsessive-compulsive disorders ultimately may develop.
The researchers now are looking at how orphanin FQ/nociceptin works on parts of the brain to alleviate stress and what controls the genes that help produce orphanin FQ/nociceptin.
"By looking further at how mice that lack the protein fail to adapt to stress, we may be able to determine exactly how orphanin FQ/nociceptin works against the stress-inducing hormones and neurotransmitters in the brain," Reinscheid said. "Eventually, knowing how this protein works could provide us with new drugs or other therapies that treat mental illnesses that are often caused by prolonged stress."
The UCI researchers were assisted by Anja Koester, Francois Jenck and Jean-Luc Moreau at Hoffman-La Roche in Basel, Switzerland; Alexandra Montkowski, Eva-Maria Stuebe and Kristina Knaudt of the University of Hamburg, Germany, and Stefan Schulz of Otto-von-Guericke University, Magdeburg, Germany.
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Contact: Andrew Porterfield (949) 824-3969 [email protected]
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