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DURHAM, N.C. — Studies with rats have revealed that
adolescents and female adults show less sensitivity to the
sedative effects of alcohol than do adult males, according to
scientists at Duke University Medical Center. They said the
animals are similar enough to humans that their findings offer
significant insight into how the human brain may react to
alcohol. For example, they said, their findings may help to
explain why adolescents under the influence of alcohol may be
more likely to engage in risky behavior -- they are less
sedated. Also, said the researchers, their findings may help
explain why women are less likely to become addicted to
alcohol.

Particularly interesting, the researchers said, is that the
sex differences appear to extend to the cellular level – a
finding not previously reported. The team's findings appear in
the January 2006 issue of Alcoholism: Clinical &
Experimental Research.

According to the team, research in humans shows that while
women typically consume less alcohol than men, they are more
susceptible to negative health consequences such as cognitive
impairment, heart disease and cirrhosis of the liver due to its
effects. A greater understanding of such a sex difference could
improve efforts to educate people about the dangers of alcohol
and perhaps eventually to a better understanding of the
mechanisms of addiction, said the researchers.

"Despite the fact that men outnumber women in terms of
having alcohol-related problems, women are more vulnerable to
the effects of alcohol use," said Young May Cha, a researcher
in psychiatry and behavioral sciences at Duke University
Medical Center and lead author on the study. "In both humans
and animal models, females can drink less and for a shorter
period of time, and yet experience the same level of effects
produced in males. This 'telescoping' phenomenon strongly
suggests that there is something unique about females that lend
them to being so susceptible to alcohol's effects."

In their studies, the researchers analyzed whether alcohol
dosages at various stages of the estrous cycle (menstrual
cycle) of female rats would produce differing effects on
behavior or brain physiology. In the behavioral study, the
researchers gave the animals a dosage of alcohol and tested the
ability of the animals to right themselves onto all four paws.
The researchers subsequently examined the neural activity in
the animals' brain tissue. They found distinct differences not
only between adolescents and adults, but also between males and
females. Separate studies of brain physiology showed that these
age and sex differences can also be observed at the cellular
level.

Specifically, the researchers found that adolescent male and
female rats were similarly sedated by the alcohol and showed
less sensitivity to its sedative effects than did adults.
However, adult male and female rats were not similarly sedated.
The researchers found that, after controlling for body weight,
adult female rats were less sensitive to the sedating effects
of alcohol, particularly in the first (proestrous) and last
(diestrous) phases of the estrous cycle.

The researchers note that the cycle stage does not appear to
be a main determinant of alcohol's sedative effects, as they
only examined brain tissue taken during two stages of the rats'
four estrous cycle stages. However, they said, a different
protocol design and additional research could prove otherwise
because scientists still do not fully understand what role the
estrous cycle might play in the central nervous system or how
alcohol is absorbed, distributed, metabolized and ultimately
eliminated from the body.

When the team measured relevant electrical activity in the
animals' hippocampus (a region of the brain that is
particularly important for learning and memory) they found a
more powerful effect in cells from male rats than in those from
females – indicating that the neurons from females were less
sensitive to this effect of alcohol.

"Because of their size and body composition, women achieve
higher blood alcohol concentrations than men and appear to 'get
drunk' more easily," said Scott Swartzwelder, Ph.D., a
professor of psychiatry at Duke and the Durham Veterans Affairs
Medical Center and senior author on the study. "This has led to
the popular belief that women are more susceptible to the
effects of alcohol than men. But when we just looked at the
effects of alcohol on the brain, we found that the female brain
was actually less sensitive. We know that women are less likely
than men to get addicted to alcohol. It could be that this
difference in brain sensitivity has something to do with the
difference in addictive liability."

Swartzwelder added that the differences between adolescent
and adult rats illuminate an important difference in humans, as
well.

"Adolescents are less sedated by alcohol, but have their
cognitive functions impaired more by alcohol than do adults,"
he said. "This means that while an adolescent may be less
sleepy than an adult after a particular dose of alcohol, they
may feel they can drive or engage in other complex activities.
Although they are not sleepy, and thus believe they are
unimpaired, they may actually be more impaired than the adult
on the kinds of complex cognitive tasks that driving
involves."

Cha added, "As humans mature from adolescence into
adulthood, women may become less sensitive to alcohol-induced
sedation than men do. This change may have consequences for the
ability of an adult woman to physiologically gauge how impaired
she is becoming as she drinks."

The research was funded via grants received from the
National
Institute on Alcohol Abuse and Alcoholism and the Institute
for Medical Research, as well as a Veterans Affairs Research
Career Scientist Award.

Other authors on the article include Quang Li, M.D., Ph.D.,
and Wilkie Wilson, Ph.D., both of Duke University Medical
Center and the Veterans Affairs Medical Center, Durham,
N.C.