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Alcohol & LTP

Neuroscientists at Washington University School of Medicine in St. Louis have identified the brain cells involved in alcohol-related blackouts and the molecular mechanism that appears to underlie them. Allcohol interferes with key receptors in the brain, which in turn manufacture steroids that inhibit long-term potentiation, a process that strengthens the connections between neurons and is crucial to learning and memory.

DRINKING TOO MUCH ALCOHOL CAN LEAD TO BLACKOUTS WHERE A PERSON CAN’T REMEMBER WHAT THEY DID DURING SEVERAL MINUTES OR HOURS WHILE DRINKING. IT’S BEEN KNOWN FOR YEARS THAT ALCOHOL CAN CAUSE BLACKOUTS, BUT THE BIOLOGY OF BLACKOUTS HAS BEEN POORLY UNDERSTOOD. NOW WASHINGTON UNIVERSITY NEUROSCIENTISTS HAVE UNCOVERED WHAT MAY BE THE MECHANISM. JIM DRYDEN HAS MORE…

WHEN WE DRINK ALCOHOL, IT GETS INTO THE BRAIN AND INTERFERES WITH RECEPTORS ON BRAIN CELLS CALLED NMDA RECEPTORS. ALCOHOL TAMPS DOWN THEIR ACTIVITY, BUT IT DOESN’T BLOCK IT COMPLETELY. SO RESEARCHERS KNEW THAT NMDA RECEPTORS DIDN’T TELL THE WHOLE STORY WHEN IT CAME TO BLACKOUTS. ACCORDING TO WASHINGTON UNIVERSITY NEUROSCIENTIST CHARLES ZORUMSKI, BLACKOUTS OCCUR WHEN SOMETHING LIKE ALCOHOL, OR ETHANOL AS SCIENTISTS CALL IT, INTERFERES WITH A PROCESS CALLED LONG-TERM POTENTIATION, OR LTP.

(act) :22 o/c clinical blackout

The belief is that LTP is a synaptic mechanism that underlies

memory formation in the hippocampus. So the idea that ethanol

blocks LTP is a potential mechanism, as a matter of fact it’s

probably the leading mechanism to explain why individuals who

get highly intoxicated with ethanol sometimes don’t remember

what they did the night before…the kind of “clinical blackout.”

THE FIRST THING ETHANOL DOES IS BLOCK SOME, BUT NOT ALL, NMDA RECEPTORS, WHICH TRANSMIT GLUTAMATE FROM NEURON TO NEURON. BUT THAT’S NOT ENOUGH TO BLOCK LTP, ACCORDING TO CO-INVESTIGATOR YUKI IZUMI. ANOTHER STEP IS NEEDED. AND THAT STEP, HE SAYS, APPEARS TO BE THE LATER PRODUCTION OF STEROIDS BY NEURONS.

(act) :17 o/c by finasteride

It is widely known that ethanol inhibits NMDA receptors, but this

is not responsible for LTP inhibition. In the presence of ethanol,

we have a lot of neurosteroids here. This increase of ethanol

production is clearly blocked by finasteride.

FINASTERIDE IS A DRUG THAT’S COMMONLY PRESCRIBED FOR MEN WITH ENLARGED PROSTATE GLANDS. IT INTERFERES WITH STEROID PRODUCTION, AND THAT’S HOW IT SEEMS TO PRESERVE LTP IN THE BRAIN. BUT WHEREAS THAT DRUG PREVENTS THE MANUFACTURE OF STEROIDS BY BRAIN CELLS, ZORUMSKI SAYS STRESS AND OTHER DRUGS CAN LEAD TO GREATER PRODUCTION OF THOSE STEROIDS.

(act) :23 o/c of LTP

By itself, it takes a lot of ethanol to block LTP, but what’s

not discussed so much, even in the manuscript, is that if there’s

other ways to turn on steroid production – other drugs will cause

steroids to go up – now in the presence of other agents that increase

steroids, it may be that lower levels of alcohol actually now lead to

a block of LTP.

AND ZORUMSKI SAYS IT’S IMPORTANT TO REMEMBER THAT ALCOHOL CAN CAUSE BLACKOUTS NOT BY KILLING NEURONS, BUT SIMPLY BY INHIBITING THIS MEMORY FORMATION MECHANISM CALLED LTP.

(act) :31 o/c new associations

If someone is heavily intoxicated, they can still do all kinds of

behaviors, like drive their car or whatever, things like that, but

they just don’t recall it. Even at this high level of ethanol that

inhibits LTP, it doesn’t block basal synaptic transmission in the

hippocampus and probably other regions of the brain. But it’s

interfering with the synaptic plasticity that’s necessary for

memories to be laid down, at least the initial stage of memory

formation. So you’re processing information. It’s just you’re

not forming new memories, new associations.

ZORUMSKI AND HIS COLLEAGUES REPORT THEIR FINDINGS ON ALCOHOL AND MEMORY IN THE JOURNAL OF NEUROSCIENCE. I’M JIM DRYDEN…

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