Alcohol alters prefrontal cortex activity through ion channel disruption

“Our major finding was that alcohol, at concentrations that are associated with mild to moderate intoxication – blood alcohol levels of 0.08 percent and above – significantly inhibited the function of the NMDA receptor ion channel without affecting AMPA or GABA ion channels,” said Woodward.

“Our results provide an explanation for how alcohol affects the ability of the prefrontal cortex to carry out its normal duties,” he said. “When NMDA receptors are inhibited, as with alcohol, the ability of the neuron to carry out its task is affected, thereby reducing the ability of an individual to control their behavior and possibly leading them to engage in actions that are not beneficial. In other words, the normal risk/benefit assessment that this brain region engages in is disrupted.”

“While potent alcohol effects on NMDA receptors (NMDAR) and NMDAR-mediated transmission have been seen in past studies in other brain regions,” added David Lovinger, chief of the Laboratory for Integrative Neuroscience at the National Institute on Alcohol Abuse and Alcoholism, “what stands out about this paper is that this effect is seen in the absence of alterations in other aspects of transmission. This selectivity is more pronounced than what has been seen in brain areas such as the hippocampus, amygdala and cerebellum.”

Lovinger said that targeting this receptor with pharmacological agents might be an effective strategy for treating problems of alcohol abuse and alcoholism, particularly if future research could identify the specific subtype of NMDAR affected by alcohol. “It would also be helpful to determine if the alcohol effects on NMDA receptors contribute to neuroadaptations or neurotoxicity in this brain region after prolonged ethanol exposure, thereby contributing to alcoholism and alcoholic brain damage.”

“These types of studies are important because they show that alcohol has specific effects on ion channels that control the activity of neurons,” observed Woodward. “This means that it is possible to determine how alcohol causes its effects on the brain, to understand how these changes lead to uncontrolled drinking and, eventually, to develop better treatments for alcoholism.”

Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. The co-author of the ACER paper, “Ethanol Selectively Attenuates NMDAR-mediated synaptic transmission in the prefrontal cortex,” was Carl Weitlauf of the Department of Neurosciences, and the Center for Drug and Alcohol Programs, at the Medical University of South Carolina. The study was funded by the Charleston Alcohol Research Center; one of 15 centers nationwide that are supported by the National Institute on Alcohol Abuse and Alcoholism.