Alcohol alters prefrontal cortex activity through ion channel disruption

N-methyl-D-aspartic acid receptors are especially sensitive to alcohol disruption

• The prefrontal cortex (PFC) region of the brain is involved in decision making.
• New rodent findings show that PFC neuron N-methyl-D-aspartic acid (NMDA) receptors are especially sensitive to concentrations of alcohol achieved during drinking.
• This suggests that alcohol’s alteration of NMDA receptor function may inhibit normal PFC function.

Researchers have long believed that abnormal function in the prefrontal cortex (PFC) region of the brain contributes to the impulsive behavior and lack of control over drinking that characterize alcohol dependence, but how this occurred was unknown. This study used rodents to examine the effects of alcohol on three specific ion channels that control the activity of PFC neurons, finding that N-methyl-D-aspartic acid (NMDA) receptors are especially sensitive to alcohol disruption.

Results are published in the April issue of Alcoholism: Clinical & Experimental Research.

“The prefrontal cortex is a part of the brain that helps us decide whether we should take actions or not,” said John J. Woodward, a professor in the department of neurosciences and the Center for Drug and Alcohol Programs at the Medical University of South Carolina. “It weighs the relative risks and benefits of our behavior and normally protects us from risky or dangerous actions or those that may be inappropriate during social situations. When the PFC is damaged or its activity is decreased, behavior can change dramatically and people can lose much of their inhibition and ability to weigh the consequences of their actions.”

Woodward, also the corresponding author for the study, explained that ion channels are gates in the neuron membrane that let ions into and out of the cells when appropriate. “We reasoned that alcohol may affect one or more of these ion channel gates, leading to alterations in the function of the prefrontal cortex … and that this may contribute to an individual’s inability to control their drinking,” he said. “This may help to explain why many alcoholics appear to lose control over their drinking despite serious adverse consequences that can arise, such as loss of job, family or even health.”

Researchers used general anesthesia to humanely euthanize male Sprague-Dawley rats. Their brains were quickly removed, chilled, sliced, and placed in a chamber for recording electrical activity. Using sophisticated single-cell neuron recording techniques, the researchers measured currents carried by NMDA, gamma-aminobutyric acid (GABA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the absence and presence of alcohol.