Alcohol Inhibits Key Brain Proteins

Although scientists have known for years that cocaine, marijuana, and heroin interact with specific proteins in the brain, they have traditionally thought that 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.

"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 university's 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."

The new study sought to induce and block Fos protein in brain as measured with Fos-like immunohistochemistry (Fos-LI), Dr. Knapp said. Fos proteins are 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.

Alcohol's main effect was to inhibit or prevent NMDA-induced Fos protein induction, Dr. 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 the hippocampus, which are essential for memory formation and higher mental functions.

"Our findings provide new evidence for the interaction of alcohol with specific neurotransmitter receptors of the living brain," he said, and noted that the results should contribute to a clearer picture of how alcohol affects the brain and leads to addiction.

He mentioned that a significant part of the motivation for the work at the Bowles Center for Alcohol Studies comes from the understanding that alcoholism is a brain disease with a neurobiological basis, not a moral failure or a lack of willpower.

NMDA receptors have gained special attention in regard to memory, 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," Dr. 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."

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