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Alcohol's legendary sedative effects may be caused
by a brain steroid derived from progesterone that damps down anxiety.
This could help explain why alcohol makes people feel so relaxed, and
why men and women react to alcohol differently.
It only takes a few drinking sessions for revellers
to get acquainted with alcohol's effects. Scientists, though, have had
a harder time figuring out exactly how the drug works on the brain. Alcohol
appears to interact with two brain receptors, one of which, the GABA receptor,
is exploited by tranquilizers such as Valium. But it is not clear exactly
how alcohol interacts with this receptor.
Animal studies show that stress increases levels
of the brain steroid allopregnanolone, which acts on the GABA receptor
to reduce anxiety. Because alcohol triggers the release of stress hormones
like corticosterone, and progesterone, from which allopregnanolone is
derived, Morrow's team suspected that drinking might also increase levels
of the steroid.
To find out, the researchers gave rats moderate
doses of ethanol roughly equivalent to the amount of alcohol someone might
consume at a cocktail party. When they removed each animal's cerebral
cortex after 20 minutes, the rats given alcohol showed dramatic rises
in allopregnanolone levels compared to rats given saline.
Was the steroid responsible for alcohol's sedative
effect? Investigators then treated rats with a drug called finasteride,
which blocks the formation of allopregnanolone from progesterone, before
giving them another drink. Alcohol usually lowers electrical activity
in a number of areas in the brain, but finasteride prevented this, indicating
that allopregnanolone does play a role in the relaxing effects of alcohol.
The investigators believe that allopregnanolone
is very important for the anticonvulsant and sedative effects of alcohol.
Perhaps women need to drink less to get the rewarding effects of alcohol
because they naturally have higher levels of the steroid. That could explain
why women are less likely to become alcoholics than men. Investigators
have previously shown that female rats drink more ethanol during the phase
in their reproductive cycle when progesterone levels are low.
The Journal of Neuroscience
March 2000 (vol 20, p 1982)
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