Neuroscientists have unlocked the secret behind alcohol-induced amnesia, otherwise known as a “blackout,” which can last anywhere from a few minutes to several hours.
According to researchers at Washington University School of Medicine in St. Louis, consuming large amounts of alcohol does not necessarily destroy brain cells as once believed.
Instead, alcohol interferes with certain receptors in the brain, which then produce steroids that hinder long-term potentiation (LTP), a process that strengthens neuron connections and is critical for learning and memory.
“The mechanism involves NMDA receptors that transmit glutamate, which carries signals between neurons,” says Yukitoshi Izumi, MD, PhD, research professor of psychiatry at Washington University School of Medicine in St. Louis.
“An NMDA receptor is like a double-edged sword because too much activity and too little can be toxic. We’ve found that exposure to alcohol inhibits some receptors and later activates others, causing neurons to manufacture steroids that inhibit LTP and memory formation.”
Izumi notes that the different receptors involved in this process interfere with synaptic plasticity in the hippocampus — a region of the brain important in cognitive function.
Izumi and first author Kazuhiro Tokuda, MD, research instructor of psychiatry, treated rat hippocampal cells with moderate amounts of alcohol and found that LTP was not affected; however, exposing the cells to large amounts of alcohol inhibited the memory formation mechanism.
“It takes a lot of alcohol to block LTP and memory,” says senior investigator Charles F. Zorumski, MD, the Samuel B. Guze Professor and head of the Department of Psychiatry.
“But the mechanism isn’t straightforward. The alcohol triggers these receptors to behave in seemingly contradictory ways, and that’s what actually blocks the neural signals that create memories. It also may explain why individuals who get highly intoxicated don’t remember what they did the night before.”
Not all NMDA receptors are blocked by alcohol — instead, their activity is cut approximately in half.
“The exposure to alcohol blocks some NMDA receptors and activates others, which then trigger the neuron to manufacture these steroids,” Zorumski says.
The researchers emphasize that alcohol doesn’t trigger blackouts by killing neurons. Instead, the steroids interfere with synaptic plasticity to hinder LTP and memory formation.
“Alcohol isn’t damaging the cells in any way that we can detect,” Zorumski says. “As a matter of fact, even at the high levels we used here, we don’t see any changes in how the brain cells communicate. You still process information. You’re not anesthetized. You haven’t passed out. But you’re not forming new memories.”
Memory formation is also blocked through the consumption of other drugs. When combined, alcohol and certain other drugs are far more likely to trigger blackouts than either substance alone.
The scientists discovered that certain drugs, called 5-alpha-reductase inhibitors, block the manufacturing of steroids and in turn preserve LTP in the rat hippocampus. These include the drugs finasteride and dutasteride, which are often prescribed to reduce an enlarged prostate gland. In the brain, however, those substances seem to sustain memory.
The team plans to study 5-alpha-reductase inhibitors to determine whether these drugs, and similar substances, may be able to play a role in preserving memory.
The study is published in The Journal of Neuroscience.