University of Pittsburgh
August 5, 1998

PITT NEUROSCIENTISTS HELP DISCOVER LINK TO BRAIN DISEASE AND DRUG ABUSE

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PITTSBURGH, Aug. 6 -- Researchers at the University of Pittsburgh, in association with ten other research institutions, hospitals and universities worldwide, have discovered the function of a gene product that plays a central role in regulating how the brain uses the neurotransmitter dopamine. Their findings appear in the August 7 issue of the journal Science.

Dopamine, a chemical that mediates the transmission of nerve impulses in the brain, has a profound effect on the way signals are transmitted between brain cells, or neurons. When there is a malfunction in the specific neurons that are activated by dopamine, several neurological and psychiatric diseases can occur, including Parkinson's, schizophrenia and psychostimulant drug abuse.

Pitt neuroscience and psychiatry professor Tony Grace, along with assistant professor Shao-Pii Onn, working as part of a broad-based international research team, looked specifically at the electrophysiology, or electrical signals, in genetically altered mice, called "genetic knockouts." The mice are engineered to have a specific gene removed, or knocked out, in this case a gene that codes for the protein DARPP-32, found in brain cells and thought to play some role in mediating the actions of dopamine.

The principle investigator for the study, Paul Greengard of Rockefeller University in New York, put together a vast collection of neuroscientists to study every aspect of DARPP-32's role in dopamine neurotransmission. Scientists from Pitt, Yale, Harvard, the College de France, Massachusetts General Hospital, the U.S. Environmental Protection Agency, Chicago Medical School, Florida State University, the University of Tennessee and Hoechst Marion Roussel, Inc., studied the knockout mice to understand everything they could about their molecular, electrophysiological and behavioral responses to dopamine.

"These mice show profound deficits in their responses to dopamine, it's clear that the gene DARPP-32 plays a profound role in the way dopamine works in the brain." said Grace. "This could be useful in the areas of developing pharmaceuticals to treat a variety of neurological disorders." Because the mice also showed less response to drugs that work through the dopamine system, like cocaine, amphetamines and methamphetamines, it could also help to understand and treat drug abuse.

"This is definitely basic research," said Grace, "but it gives us much greater knowledge about just what kind of mechanisms are at work in the brain at the cellular level, and gives us some insight into how to change those mechanisms when necessary."

Being included in this study is also an indication of the quality of neuroscience at the University of Pittsburgh. "We have a very strong neuroscience department at Pitt, especially in dopamine neurotransmitter research," said Grace. "To be included in the select group that conducted this study reflects well on the reputation of Pitt neuroscience."

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