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In what is considered a significant step toward understanding how addiction to alcohol can occur, scientists at the university have discovered a mechanism linking a previously identified neuroprotein to the effects of alcohol on the brain.

Richard Morrisett, an associate professor of pharmacology, and his research team at the Waggoner Center for Alcohol and Addiction Research and the College of Pharmacy have identified the involvement of the neuroprotein, DARPP-32, as a key element initiating ethanol addiction.

These findings will be published in the July issue of Nature Neuroscience and online at the Nature Neuroscience Web site.

DARPP-32 was identified by a Nobel laureate in the 1980s, but Morrisett says his research team is the first to establish a tie between DARPP-32 and the molecular mechanism within the brain that stimulates addiction to alcohol.
Discovery of the link, he said, is the first step toward understanding the seemingly contradictory nature of alcohol effects that has stymied researchers.

“Alcohol is a known depressant or inhibitor of brain function,” said Regina Maldve, a research associate in the College of Pharmacy and a member of the team. “For years scientists have struggled to understand how an inhibitor can act to stimulate the brain responses which promote addiction to alcohol.”

The university researchers say the one clue in solving the puzzle appears to be DARPP-32.

“Scientists determined in 1989 that alcohol works to inhibit the NMDA (protein) receptors which appear to be critical for addiction to this drug,” said Morrisett. “Many of us have worked over the past 13 years or so to understand how this works and how addiction could result from inhibition of this receptor.

"This paper is the first to identify DARPP-32 and its ability to regulate ethanol effects on NMDA receptors. The research leads us to believe that DARPP-32 initiates alterations that influence the brain's response to alcohol.”

Rueben Gonzales, a university professor of pharmacology and co-author of the study, agrees the new finding is a milestone in the field of alcoholism research.

"Our work is a significant step in identifying how alcohol changes brain function in the process that may lead to alcoholism," he said.

Work in Morrisett’s laboratory is supported by grants from the National Institute for Alcohol Abuse and Alcoholism, the Texas Commission on Alcohol and Drug Abuse, and the university's Waggoner Center.