Over the course of two years, the researchers in his laboratory "designed" and studied a strain of mice lacking the Gz protein, enabling them to conduct simultaneous research on the animals' blood systems and brain activities.

"Our long-range goal is to understand what can be done to prevent platelets from being activated in the area of an injury. But at the same time, the research also helps us understand what's involved when people abuse psychoactive drugs such as cocaine and morphine," Brass said.

"It's a step to understanding how to make better pain-killers for people suffering intractable pain," he said. "Understanding this stuff is not a trivial intellectual exercise."

The researchers found, for instance, that in the animals the Gz protein conveys signals from epinephrine -- a hormone that stimulates the nervous system and accelerates the heart rate and enhances blood-clotting.

In the study, the specialized animals' response to cocaine was increased, although their response to morphine was reduced, Yang said.

Even more significantly, when the mice were administered drugs from the series of anti-depressants known as catecholamine reuptake inhibitors (desipramine, and reboxetine), "they didn't respond at all," she said.

"We don't have data for humans yet, but the basic mechanism may be the same in both human and mice models," Yang said. "What we can do is conduct some biochemical and pharmacological studies, to see whether the slight variations that exist will affect the influence of the protein. If the same thing is true for humans, it opens up a whole new field for the discovery of new drugs."

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Contact: Ellen O'Brien
obriene@uphs.upenn.edu
215-349-5659
University of Pennsylvania School of Medicine
4-Sep-2000