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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.