Epidemiological data of alcohol drinking patterns in the U.S. suggest men are more likely to drink alcohol, drink heavily, and have more legal and psychosocial problems related to their consumption of alcohol compared to women. The biological basis for these gender differences in problem drinking is unknown. It is possible that there are gender differences in either vulnerability to the reinforcing effects of ethanol or sensitivity to the behavioral effects of ethanol; these differences could, in turn, result in differential alcohol consumption. Although some studies suggest that the consumption of alcohol is influenced by menstrual cycle phase, the relationship between reproductive function and alcohol is difficult to study in human being for ethical, logistic, and financial reasons. It is also difficult to study changes in behavior over the menstrual cycle in women because both experimenter and subject bias may affect the outcome of the study. Likewise, behavioral responses to alcohol are difficult to study because expectations about the effects of alcohol on behavior strongly influence social and affective behavior. An alternative is to circumvent examining these difficulties by using an appropriate animal model. Macaques are a useful model because they develop blood alcohol levels similar to human beings in response to a given dose, they metabolize alcohol at approximately the same rate as human beings, they can be trained to self-administer alcohol in significant amounts, they rely on complex social relationships, they are capable of complex cognitive function, and females have menstrual cycles that are similar in length and pattern of gonadotropin and sex steroid secretion to those of women. In addition, while reports are variable, the majority of the available data suggests that several broad classes of behavior (e.g., aggression, affiliation, food intake, sexual interaction, and social withdrawal) vary with the menstrual cycle in macaques. Behavioral variability coincident with menstrual cyclicity provides the potential plasticity necessary to observe female reproductive function effects on alcohol consumption and on associated behavioral responses. We propose to investigate the effects of gender, menstrual cycle phase, ethanol dose, and social setting on oral ethanol self-administration and behavior in this nonhuman primate model.
