November 2001

From University of North Carolina at Chapel Hill

Scientists find new evidence for specific actions of alcohol in brain

(Embargoed) CHAPEL HILL – Although scientists have known for years that cocaine, marijuana and heroin interact with specific proteins in the brain, traditionally they have thought alcohol had no such pointed effects.

Now University of North Carolina at Chapel Hill researchers have found evidence that alcohol inhibits the actions of key proteins called N-methyl-D-aspartic acid (NMDA) receptors in specific regions of the brain.

A report on their work appears Thursday (Nov. 15) in the November issue of the journal Alcoholism: Clinical & Experimental Research.

“NMDA receptors in the brain are key sites of action of the neurotransmitter glutamate, which increases the activity of brain neurons,” said lead author Dr. Darin J. Knapp, research assistant professor of psychiatry at the UNC School of Medicine. “Earlier investigations have shown that alcohol-NMDA interactions influence many features of alcohol exposure, including effects on fetal development, seizures, gene expression in brain, intoxication, tolerance to ethanol and alcohol dependence.”

Conducted on rats, the new study sought to induce and block Fos protein in brain as measured with Fos-like Immunohistochemistry (Fos-LI), Knapp said. Fos proteins belong to a family of proteins known to reflect changes in cellular activity and participate in regulating gene activity.

Measurement of Fos-LI is a form of brain mapping that allows researchers to identify and note brain regions that change their activity after different challenges, such as alcohol consumption, he said.

Researchers gave rats NMDA or alcohol by various routes to determine brain responses.

Alcohol’s main effect was to inhibit or prevent NMDA-induced Fos protein induction, Knapp said. That means Fos protein induction by NMDA -- and the blockage caused by alcohol -- occurred in specific brain regions such as the prefrontal cortex and hippocampus, which are key to memory formation and higher mental functions.

“Our findings provide new evidence for the interaction of alcohol with specific neurotransmitter receptors of the living brain,” Knapp said.

The results will contribute to a clearer picture of how alcohol affects the brain and leads to addiction, he said.

“A significant part of the motivation for our work here at the Bowles Center for Alcohol Studies comes from the understanding that alcoholism is a brain disease with a neurobiological basis and not a moral failure or a lack of willpower,” the scientist said.

Recently, NMDA receptors gained special attention when their importance for memory formation was shown, said Dr. Andrey Ryabinin, assistant professor of behavioral neuroscience at the Oregon Health Sciences University.

“One of the features of alcoholism and drug addiction is the formation of habits,” Ryabinin said. “There could therefore be a common link between becoming an alcoholic and developing, or learning, an alcohol-related habit, and NMDA receptors could be involved in this.”

Co-authors of the paper, all at UNC, include Drs. Fulton T. Crews, Gary E. Duncan and George R. Breese Jr., all faculty members, and technicians Christopher J. Braun, Alda Fernandes and Ying Qian. They are affiliated with the Bowles Center for Alcohol Studies, the UNC Neurosciences Center and the departments of psychiatry, pharmacology and anesthesiology in the School of Medicine.

The National Institute on Alcohol Abuse and Alcoholism funded the research.

Note: Knapp can be reached at 919-966-0505 or via e-mail: djkjas@med.unc.edu Ryabinin at 503-494-2060 or ryabinin@ohsu.edu. A copy of the manuscript is available by calling KJ at the University of Texas, 512-475-9568. Contact: David Williamson, 919-962-8596











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