Although women consume less alcohol than men, they are more susceptible to some of the negative medical consequences of alcohol use, such as cirrhosis of the liver, cardiac disease, and cognitive impairments.

Animal studies have also shown that males and females differ on behavioral as well as electrophysiological measures of alcohol’s effects. A study in the January issue of Alcoholism: Clinical & Experimental Research has found that female rats are not only less sensitive to the sedating effects of alcohol, but that cycling hormonal levels can mediate alcohol’s effects.

“Despite the fact that men outnumber women in terms of having alcohol-related problems, women are more vulnerable to many of the effects of alcohol use,” said the study’s first author, Young May Cha, a research analyst at Duke University Medical Center. “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 the female sex that lends it to being so susceptible to alcohol’s effects.”

Cha and her colleagues decided to use an animal model to examine what effects the adult females’ estrous cycles might have on alcohol’s effects. “The four stages of the rat estrous cycle can be viewed as similar to the different stages of the human menstrual cycle,” she explained. “In both humans and rats, sex hormone levels rise and fall in a cyclical pattern. Furthermore, rats are a useful and practical model to study these hormone fluctuations because the estrous cycle is relatively short; it is only four to five days long.”

Following administration of 5 g/kg alcohol, adolescent and adult male and female rats were observed for loss of the righting reflex (the ability to right themselves onto all four paws). In addition, researchers used whole-cell recordings to measure the response of spontaneous, GABAA receptor-mediated IPSCs (an inhibitory process) in brain slices from drug-na? adult males and females. This combined approach allowed researchers to describe the behavioral difference between the effects of alcohol on males and females, and also to address a possible mechanism at the cellular level.

“The promotion of GABA-mediated neuronal inhibition is thought to be a primary mechanism of alcohol-induced sedation, and may also account for some of its anti-anxiety effects,” explained Scott Swartzwelder, professor of psychiatry at Duke and senior author of the study. “This measurement is particularly significant in our study because it correlates with the result that the females are less sensitive to alcohol-induced sedation. Since these measurements are made in isolated brain sections, the effects cannot be due to sex differences in alcohol absorption or elimination in the body.”

The female rodents’ lesser sensitivity, compared with the adult males, to the behavioral sedative effects of alcohol was most pronounced in the proestrous (the first phase of the estrous cycle, which corresponds to the onset of mating behavior) and diestrous (the last phase of the estrous cycle) states.

“We know that females are affected by alcohol differently than males,” said Swartzwelder, “but unlike many studies, this one shows a way in which females are less sensitive than males. People generally think that alcohol is more potent in females, but that is because women are smaller than men and it generally takes fewer drinks for them to become impaired. Our study shows that when you control for that, and just look at the potency of alcohol on the brain mechanisms that cause sedation, females actually appear to be less sensitive to alcohol. Furthermore, the study emphasizes the need to explore how factors associated with the estrous cycle (or menstrual cycle in humans) may mediate this effect.”

Cha added that the study also shows that adolescent male and female rats are similarly sedated by alcohol, but that adult male and female rats are not. “This result suggests that as humans mature from adolescence to 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.”

Furthermore, added Cha, “although we live in a society that favors equality between the sexes, men and women are not equal when it involves being affected by alcohol. In particular, this study’s findings suggest that women, as the gender less affected by alcohol’s sedative effects, should take greater care when gauging how much they have had to drink. This study underscores the need to look more closely at the factors that cause this sex difference in alcohol effects, and emphasizes that in some ways, alcohol is less potent in females than in males. We propose that hormonal fluctuations - or substances affected by those hormonal fluctuations, such as neurosteroids - may play a role in mediating this sex difference.”

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