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 CANT REMEMBER WHAT THEY DID DURING SEVERAL MINUTES OR HOURS WHILE DRINKING. ITS 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 DOESNT BLOCK IT COMPLETELY. SO RESEARCHERS KNEW THAT NMDA RECEPTORS DIDNT 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 its
probably the leading mechanism to explain why individuals who
get highly intoxicated with ethanol sometimes dont 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 THATS 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.
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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 THATS COMMONLY PRESCRIBED FOR MEN WITH ENLARGED PROSTATE GLANDS. IT INTERFERES WITH STEROID PRODUCTION, AND THATS 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.
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By itself, it takes a lot of ethanol to block LTP, but whats
not discussed so much, even in the manuscript, is that if theres
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 ITS 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 dont recall it. Even at this high level of ethanol that
inhibits LTP, it doesnt block basal synaptic transmission in the
hippocampus and probably other regions of the brain. But its
interfering with the synaptic plasticity thats necessary for
memories to be laid down, at least the initial stage of memory
formation. So youre processing information. Its just youre
not forming new memories, new associations.
ZORUMSKI AND HIS COLLEAGUES REPORT THEIR FINDINGS ON ALCOHOL AND MEMORY IN THE JOURNAL OF NEUROSCIENCE. IM JIM DRYDEN