November 20, 2003
Learning more about how serotonin works
The way you feel right this moment, your ability to remember where you parked the car and even whether you get stressed out when you pay the bills are all dependent on the way your brain produces and releases serotonin. This autoreceptor, also known as 5-HT1B, is produced in the small part of the brain where the serotonin neurons originate, and their projections bathe every neuron in the forebrain with serotonin, producing strong effects on behavior and mood.
Dr. John Neumaier, associate professor of psychiatry and behavioral sciences in the UW School of Medicine, has been researching the effects of serotonin on depression, post-traumatic stress disorder and anxiety since he began his postdoctoral research here in 1992. Using viral-mediated gene transfer, sometimes called gene therapy, he and his laboratory colleagues have been creating a pathological state of disregulated serotonin release that parallels in lab animals the symptoms suffered by many of the patients Neumaier sees in his practice.
“While many people familiar with the brain feel that more serotonin is always good, the problem is actually more complicated,” Neumaier says. “You need to have the right amount of serotonin at the right time in the right place for the brain to function properly. One of the major ways that serotonin transmission in the brain is regulated is by autoreceptors. These are proteins that behave like bureaucrats that control the flow of serotonin.”
Neumaier had hypothesized that when too much of the 5-HT1B autoreceptor was being produced by the serotonin neurons, it would cause depression-like behavior. The results of manipulating serotonin by changing receptor activity, however, were much more complicated.
“We found that when we increased the levels of 5-HT1B autoreceptors, the animals’ response to their environment was changed. If the animal perceived that it was not in a dangerous environment, it was less anxious than usual,” Neumaier says. “If the animal had been stressed, it was more anxious than usual. Increasing the levels of these receptors increases the impact of environmental stressors on the animal’s behavior. That was not the simple story I had been hoping for.”
Neumaier will discuss the results of his lab’s research so far at the Science in Medicine Lecture from noon to 1 p.m. Thursday, Dec. 4, in Hogness Auditorium at the Health Sciences Center. This presentation, “Sorting Out Serotonin Using Viral Gene Transfer,” is free and open to everyone.
Neumaier attended Reed College in Portland, Ore., where he received a degree in biology. He subsequently received a Ph.D. in pharmacology and an M.D. from the UW School of Medicine. He served his residency and was chief resident in psychiatry at UW Medical Center. He was appointed associate professor in 2001. Among other honors, he was the recipient of the American Psychiatric Association/SmithKline Beecham Young Faculty Award in 1998 and the American College of Neuropsychopharmacology/Mead Johnson Travel Award in 1996. In 1994 Neumaier was named outstanding resident for the Department of Psychiatry and also won the Sandoz Award for Research.
